Updated on 2024/03/29

写真a

 
ONODERA Osamu
 
Organization
Brain Research Institute Professor
Title
Professor
▶ display Profile on researchmap
External link

Degree

  • 博士(医学) ( 1993.3   新潟大学 )

Research Interests

  • ポリグルタミン

  • 多系統萎縮症

  • 神経病態

  • 神経変性疾患

  • 筋萎縮性側索硬化症

  • スプライシング

  • 脊髄小脳変性症

  • DNA修復

  • intermediate filaments

  • unfolding protein

  • CREB依存性転写

  • 天然変性蛋白

  • UPS

  • MTOC

  • GFP

  • polygultamine

  • Molecular neurobiology

  • Huntington disease

  • マイクロアレイ

  • 血管性認知症

  • 炎症

  • DRPLA

  • XRCC1

  • aggresome

  • 包括脳ネットワーク

  • HTRA1

  • ALS

  • TDP-43

  • アプラタキシン

  • 核内小体

  • TGF-β

  • グリア

  • CAG繰り返し配列

  • DNA損傷修復

  • 封入体

  • 脳小血管

Research Areas

  • Life Science / Neurology

  • Life Science / Human pathology

  • Life Science / Anatomy and histopathology of nervous system

  • Life Science / Radiological sciences

Research History (researchmap)

  • 新潟大学医歯学付属病院病院長補佐

    2022.9

      More details

  • 新潟大学医歯学総合病院 副院長

    2020.7 - 2022.8

      More details

  • Niigata University   Brain Research Institute Clinical Neuroscience Branch Department of Neurology   Professor

    2020.4

      More details

  • Director of Brain Research Institute

    2020.2

      More details

  • Niigata University   Brain Research Institute Clinical Neuroscience Branch Department of Neurology   Professor

    2016.4 - 2020.3

      More details

  • Niigata University   Brain Research Institute   Professor

    2010.10 - 2016.3

      More details

  • Niigata University   Brain Research Institute   Associate Professor

    2002 - 2010

      More details

▶ display all

Research History

  • Niigata University   Brain Research Institute Clinical Neuroscience Branch   Professor

    2016.4

  • Niigata University   Brain Research Institute Center for Bioresources   Professor

    2011.10 - 2016.3

  • Niigata University   Graduate School of Medical and Dental Sciences Molecular and Cellular Medicine   Professor

    2011.10 - 2016.3

  • Niigata University   Graduate School of Medical and Dental Sciences Biomedical Sciences   Professor

    2011.10 - 2016.3

  • Niigata University   Brain Research Institute Center for Bioresources   Associate Professor

    2002.5 - 2011.9

  • Niigata University   Brain Research Institute   Research Assistant

    1998.5 - 2002.4

  • Niigata University   University Medical Hospital

    1997.11 - 1998.4

▶ display all

Education

  • Niigata University   医学研究科

    1989.4 - 1993.3

      More details

    Country: Japan

    researchmap

  • Niigata University   Faculty of Medicine

    1981.4 - 1987.3

      More details

    Country: Japan

    researchmap

Professional Memberships

▶ display all

Committee Memberships

  • Neurochemistry International   Associate Editor  

    2018.8   

      More details

    Committee type:Academic society

    researchmap

  • 日本神経学会   理事  

    2018.5   

      More details

    Committee type:Academic society

    researchmap

  • 日本認知症学会   理事  

    2017.10   

      More details

    Committee type:Academic society

    researchmap

 

Papers

  • TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models. International journal

    Shintaro Tsuboguchi, Yuka Nakamura, Tomohiko Ishihara, Taisuke Kato, Tokiharu Sato, Akihide Koyama, Hideki Mori, Yuka Koike, Osamu Onodera, Masaki Ueno

    Acta neuropathologica   2023.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that primarily induced TDP-43 inclusions in the corticospinal neurons, spinal motor neurons, or forelimb skeletal muscle, by using adeno-associated virus (AAV) expressing mutant TDP-43. We found that TDP-43 induced in the corticospinal neurons was transported along the axons anterogradely and transferred to the oligodendrocytes along the corticospinal tract (CST), coinciding with mild axon degeneration. In contrast, TDP-43 introduced in the spinal motor neurons did not spread retrogradely to the cortical or spinal neurons; however, it induced an extreme loss of spinal motor neurons and subsequent degeneration of neighboring spinal neurons, suggesting a degenerative propagation in a retrograde manner in the spinal cord. The intraspinal degeneration further led to severe muscle atrophy. Finally, TDP-43 induced in the skeletal muscle did not propagate pathological events to spinal neurons retrogradely. Our data revealed that mutant TDP-43 spread across neuro-glial connections anterogradely in the corticospinal pathway, whereas it exhibited different retrograde degenerative properties in the spinal circuits. This suggests that pathogenic TDP-43 may induce distinct antero- and retrograde mechanisms of degeneration in the motor system in ALS.

    DOI: 10.1007/s00401-023-02615-8

    PubMed

    researchmap

  • Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease. International journal

    Hideaki Matsui, Shinji Ito, Hideki Matsui, Junko Ito, Ramil Gabdulkhaev, Mika Hirose, Tomoyuki Yamanaka, Akihide Koyama, Taisuke Kato, Maiko Tanaka, Norihito Uemura, Noriko Matsui, Sachiko Hirokawa, Maki Yoshihama, Aki Shimozawa, Shin-Ichiro Kubo, Kenji Iwasaki, Masato Hasegawa, Ryosuke Takahashi, Keisuke Hirai, Akiyoshi Kakita, Osamu Onodera

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 23 )   e2214652120   2023.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD.

    DOI: 10.1073/pnas.2214652120

    PubMed

    researchmap

  • Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model. Reviewed International journal

    Taisuke Kato, Ri-Ichiroh Manabe, Hironaka Igarashi, Fuyuki Kametani, Sachiko Hirokawa, Yumi Sekine, Natsumi Fujita, Satoshi Saito, Yusuke Kawashima, Yuya Hatano, Shoichiro Ando, Hiroaki Nozaki, Akihiro Sugai, Masahiro Uemura, Masaki Fukunaga, Toshiya Sato, Akihide Koyama, Rie Saito, Atsushi Sugie, Yasuko Toyoshima, Hirotoshi Kawata, Shigeo Murayama, Masaki Matsumoto, Akiyoshi Kakita, Masato Hasegawa, Masafumi Ihara, Masato Kanazawa, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    The Journal of clinical investigation   131 ( 22 )   2021.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

    DOI: 10.1172/JCI140555

    PubMed

    researchmap

  • Age-related demethylation of the TDP-43 autoregulatory region in the human motor cortex. International journal

    Yuka Koike, Akihiro Sugai, Norikazu Hara, Junko Ito, Akio Yokoseki, Tomohiko Ishihara, Takuma Yamagishi, Shintaro Tsuboguchi, Mari Tada, Takeshi Ikeuchi, Akiyoshi Kakita, Osamu Onodera

    Communications biology   4 ( 1 )   1107 - 1107   2021.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43), which is encoded by TARDBP, forms aggregates in the motor cortex. This aggregate formation may be triggered by an increase in the TDP-43 level with aging. However, the amount of TDP-43 is autoregulated by alternative splicing of the TARDBP 3'UTR, and how this autoregulation is affected by aging remains to be elucidated. We found that DNA demethylation in the autoregulatory region in the TARDBP 3'UTR reduced alternative splicing and increased TARDBP mRNA expression. Furthermore, in the human motor cortex, we found that this region was demethylated with aging, resulting in increased expression of TARDBP mRNA. The acceleration of DNA demethylation in the motor cortex was associated with the age of ALS onset. In summary, the dysregulation of TDP-43 autoregulation by age-related DNA demethylation in the motor cortex may explain the contribution of aging and motor system selectivity in ALS.

    DOI: 10.1038/s42003-021-02621-0

    PubMed

    researchmap

  • TDP-43 transports ribosomal protein mRNA to regulate axonal local translation in neuronal axons. Reviewed International journal

    Seiichi Nagano, Junki Jinno, Rehab F Abdelhamid, Yinshi Jin, Megumi Shibata, Shohei Watanabe, Sachiko Hirokawa, Masatoyo Nishizawa, Kenji Sakimura, Osamu Onodera, Hironori Okada, Takashi Okada, Yuko Saito, Junko Takahashi-Fujigasaki, Shigeo Murayama, Shuji Wakatsuki, Hideki Mochizuki, Toshiyuki Araki

    Acta neuropathologica   140 ( 5 )   695 - 713   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Mislocalization and abnormal deposition of TDP-43 into the cytoplasm (TDP-43 proteinopathy) is a hallmark in neurons of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the pathogenic mechanism of the diseases linked to TDP-43 is largely unknown. We hypothesized that the failure of mRNA transport to neuronal axons by TDP-43 may contribute to neurodegeneration in ALS and FTLD, and sought to examine the function of TDP-43 by identifying its target mRNA for axonal transport. We found that mRNAs related to translational function including ribosomal proteins (RPs) were decreased by shRNA-based TDP-43 knock-down in neurites of cortical neurons. TDP-43 binds to and transports the RP mRNAs through their 5' untranslated region, which contains a common 5' terminal oligopyrimidine tract motif and a downstream GC-rich region. We showed by employing in vitro and in vivo models that the RP mRNAs were translated and incorporated into native ribosomes locally in axons to maintain functionality of axonal ribosomes, which is required for local protein synthesis in response to stimulation and stress to axons. We also found that RP mRNAs were reduced in the pyramidal tract of sporadic ALS cases harboring TDP-43 pathology. Our results elucidated a novel function of TDP-43 to control transport of RP mRNAs and local translation by ribosomes to maintain morphological integrity of neuronal axons, and proved the influence of this function of TDP-43 on neurodegeneration in ALS and FTLD associated with TDP-43 proteinopathy.

    DOI: 10.1007/s00401-020-02205-y

    PubMed

    researchmap

    Other Link: http://link.springer.com/article/10.1007/s00401-020-02205-y/fulltext.html

  • Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3. Reviewed International journal

    Mercedes Prudencio, Hector Garcia-Moreno, Karen R Jansen-West, Rana Hanna Al-Shaikh, Tania F Gendron, Michael G Heckman, Matthew R Spiegel, Yari Carlomagno, Lillian M Daughrity, Yuping Song, Judith A Dunmore, Natalie Byron, Björn Oskarsson, Katharine A Nicholson, Nathan P Staff, Sorina Gorcenco, Andreas Puschmann, João Lemos, Cristina Januário, Mark S LeDoux, Joseph H Friedman, James Polke, Robin Labrum, Vikram Shakkottai, Hayley S McLoughlin, Henry L Paulson, Takuya Konno, Osamu Onodera, Takeshi Ikeuchi, Mari Tada, Akiyoshi Kakita, John D Fryer, Christin Karremo, Inês Gomes, John N Caviness, Mark R Pittelkow, Jan Aasly, Ronald F Pfeiffer, Venka Veerappan, Eric R Eggenberger, William D Freeman, Josephine F Huang, Ryan J Uitti, Klaas J Wierenga, Iris V Marin Collazo, Philip W Tipton, Jay A van Gerpen, Marka van Blitterswijk, Guojun Bu, Zbigniew K Wszolek, Paola Giunti, Leonard Petrucelli

    Science translational medicine   12 ( 566 )   2020.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

    DOI: 10.1126/scitranslmed.abb7086

    PubMed

    researchmap

  • Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation. Reviewed International journal

    Eiko N Minakawa, Helena Akiko Popiel, Masayoshi Tada, Toshiaki Takahashi, Hiroshi Yamane, Yuji Saitoh, Yasuo Takahashi, Daisaku Ozawa, Akiko Takeda, Toshihide Takeuchi, Yuma Okamoto, Kazuhiro Yamamoto, Mari Suzuki, Hiromi Fujita, Chiyomi Ito, Hiroko Yagihara, Yuko Saito, Kei Watase, Hiroaki Adachi, Masahisa Katsuno, Hideki Mochizuki, Kentaro Shiraki, Gen Sobue, Tatsushi Toda, Keiji Wada, Osamu Onodera, Yoshitaka Nagai

    Brain : a journal of neurology   143 ( 6 )   1811 - 1825   2020.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases that include Huntington's disease, various spinocerebellar ataxias, spinal and bulbar muscular atrophy, and dentatorubral pallidoluysian atrophy. They are caused by the abnormal expansion of a CAG repeat coding for the polyQ stretch in the causative gene of each disease. The expanded polyQ stretches trigger abnormal β-sheet conformational transition and oligomerization followed by aggregation of the polyQ proteins in the affected neurons, leading to neuronal toxicity and neurodegeneration. Disease-modifying therapies that attenuate both symptoms and molecular pathogenesis of polyQ diseases remain an unmet clinical need. Here we identified arginine, a chemical chaperone that facilitates proper protein folding, as a novel compound that targets the upstream processes of polyQ protein aggregation by stabilizing the polyQ protein conformation. We first screened representative chemical chaperones using an in vitro polyQ aggregation assay, and identified arginine as a potent polyQ aggregation inhibitor. Our in vitro and cellular assays revealed that arginine exerts its anti-aggregation property by inhibiting the toxic β-sheet conformational transition and oligomerization of polyQ proteins before the formation of insoluble aggregates. Arginine exhibited therapeutic effects on neurological symptoms and protein aggregation pathology in Caenorhabditis elegans, Drosophila, and two different mouse models of polyQ diseases. Arginine was also effective in a polyQ mouse model when administered after symptom onset. As arginine has been safely used for urea cycle defects and for mitochondrial myopathy, encephalopathy, lactic acid and stroke syndrome patients, and efficiently crosses the blood-brain barrier, a drug-repositioning approach for arginine would enable prompt clinical application as a promising disease-modifier drug for the polyQ diseases.

    DOI: 10.1093/brain/awaa115

    PubMed

    researchmap

  • Effect of rovatirelin in patients with cerebellar ataxia: two randomised double-blind placebo-controlled phase 3 trials. Reviewed International journal

    Masatoyo Nishizawa, Osamu Onodera, Akihiro Hirakawa, Yoshitaka Shimizu, Masayuki Yamada

    Journal of neurology, neurosurgery, and psychiatry   91 ( 3 )   254 - 262   2020.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: To investigate the efficacy of rovatirelin, a thyrotropin-releasing hormone analogue, for ataxias in patients with spinocerebellar degeneration (SCD). METHODS: Two multicentre, randomised, double-blind, placebo-controlled phase 3 studies (KPS1301, KPS1305) enrolled patients with predominant cerebellar ataxia, including SCA6, SCA31 or cortical cerebellar atrophy. KPS1301 enrolled patients with truncal ataxia and KPS1305 enrolled patients with truncal and limb ataxia. Each study included 4 weeks of pretreatment, a 28-week or 24-week treatment period and 4 weeks of follow-up. Patients were randomised (1:1:1) to rovatirelin (1.6 or 2.4 mg) or placebo in KPS1301, and randomised (1:1) to rovatirelin 2.4 mg or placebo in KPS1305. The primary endpoint was change in Scale for the Assessment and Rating of Ataxia (SARA) total scores. Pooled analysis was performed in patients who met the SARA recruitment criteria of KPS1305. RESULTS: From October 2013 to May 2014, KPS1301 enrolled 411 patients; 374 were randomised to rovatirelin 1.6 mg (n=125), rovatirelin 2.4 mg (n=126) or placebo (n=123). From November 2016 to August 2017, KPS1305 enrolled 241 patients; 203 were randomised to rovatirelin 2.4 mg (n=101) or placebo (n=102). The primary endpoint showed no significant difference between rovatirelin and placebo in these two studies. In the pooled analysis (n=278), the difference between rovatirelin 2.4 mg (n=140) and placebo (n=138) was -0.61 (-1.64 vs -1.03; 95% CI -1.16 to -0.06; p=0.029) in the adjusted mean change in the SARA total score. CONCLUSIONS: Rovatirelin is a potentially effective treatment option for SCD. TRIAL REGISTRATION NUMBER: NCT01970098; NCT02889302.

    DOI: 10.1136/jnnp-2019-322168

    PubMed

    researchmap

  • Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study. Reviewed International journal

    Junko Ito, Hiroshi Shimizu, Kentaro Ohta, Jiro Idezuka, Hajime Tanaka, Hiroshi Kondo, Takashi Nakajima, Hitoshi Takahashi, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Annals of neurology   87 ( 2 )   302 - 312   2020.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype. METHODS: From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features. RESULTS: Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra. INTERPRETATION: The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302-312.

    DOI: 10.1002/ana.25652

    PubMed

    researchmap

  • HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature. Reviewed International journal

    Masahiro Uemura, Hiroaki Nozaki, Taisuke Kato, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Nozomi Hishikawa, Yoshinori Nishimoto, Kiran Polavarapu, Atchayaram Nalini, Akira Hanazono, Daisuke Kuzume, Akihiro Shindo, Mohammad El-Ghanem, Arata Abe, Aki Sato, Mari Yoshida, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    Frontiers in neurology   11   545 - 545   2020

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.

    DOI: 10.3389/fneur.2020.00545

    PubMed

    researchmap

  • Non-genetically modified models exhibit TARDBP mRNA increase due to perturbed TDP-43 autoregulation. Reviewed International journal

    Akihiro Sugai, Taisuke Kato, Akihide Koyama, Yuka Koike, Takuya Konno, Tomohiko Ishihara, Osamu Onodera

    Neurobiology of disease   130   104534 - 104534   2019.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by accumulation of fragmented insoluble TDP-43 and loss of TDP-43 from the nucleus. Increased expression of exogenous TARDBP (encoding TDP-43) induces TDP-43 pathology and cytotoxicity, suggesting the involvement of aberrant expression of TDP-43 in the pathogenesis of ALS. In normal conditions, however, the amount of TDP-43 is tightly regulated by the autoregulatory mechanism involving alternative splicing of TARDBP mRNA. To investigate the influence of autoregulation dysfunction, we inhibited the splicing of cryptic intron 6 using antisense oligonucleotides in vivo. This inhibition doubled the Tardbp mRNA expression, increased the fragmented insoluble TDP-43, and reduced the number of motor neurons in the mouse spinal cord. In human induced pluripotent stem cell-derived neurons, the splicing inhibition of intron 6 increased TARDBP mRNA and decreased nuclear TDP-43. These non-genetically modified models exhibiting rise in the TARDBP mRNA levels suggest that TDP-43 autoregulation turbulence might be linked to the pathogenesis of ALS.

    DOI: 10.1016/j.nbd.2019.104534

    PubMed

    researchmap

  • Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation. Reviewed International journal

    Rie Saito, Hiroaki Nozaki, Taisuke Kato, Yasuko Toyoshima, Hajime Tanaka, Yutaka Tsubata, Tetsuo Morioka, Yoh Horikawa, Kiyomitsu Oyanagi, Takashi Morita, Osamu Onodera, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   78 ( 2 )   181 - 186   2019.2

     More details

    Language:English  

    Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL. However, cellular expression of TREX1 in the brain and visceral organs of patients with RVCL has been unclear. Here, we report the clinicopathologic features of an autopsied patient with a heterozygous T249fs mutation in TREX1. The patient showed the clinical phenotype of vasculopathy with retinopathy, nephropathy, and stroke. CT with contrast enhancement demonstrated a tumorous lesion in the subcortical white matter. Histologically, the lesion consisted of confluent foci of necrosis with calcification and fibrous thickening of small vessel walls. TREX1 immunohistochemistry demonstrated positivity in the nuclei of cells in the CNS and visceral organs, indicating aberrant localization of the truncated protein, and the expression was remarkable in oligodendrocytes within the lesion, suggesting possible involvement of the protein in the pathomechanism of vasculopathy leading to white matter degeneration.

    DOI: 10.1093/jnen/nly115

    PubMed

    researchmap

  • HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade. Reviewed International journal

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in neurology   10   693 - 693   2019

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Background: Mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for HTRA1 mutations are asymptomatic, but more than 10 mutations have been reported in symptomatic carriers. The molecular differences between the mutations identified in symptomatic carriers and mutations identified only in CARASIL patients are unclear. HTRA1 is a serine protease that forms homotrimers, with each HTRA1 subunit activating the adjacent HTRA1 via the sensor domain of loop 3 (L3) and the activation domain of loop D (LD). Previously, we analyzed four HTRA1 mutant proteins identified in symptomatic carriers and found that they were unable to form trimers or had mutations in the LD or L3 domain. The mutant HTRA1s with these properties are presumed to inhibit trimer-dependent activation cascade. Indeed, these mutant HTRA1s inhibited wild-type (WT) protease activity. In this study, we further analyzed 15 missense HTRA1s to clarify the molecular character of mutant HTRA1s identified in symptomatic carriers. Methods: We analyzed 12 missense HTRA1s identified in symptomatic carriers (hetero-HTRA1) and three missense HTRA1s found only in CARASIL (CARASIL-HTRA1). The protease activity of the purified recombinant mutant HTRA1s was measured using fluorescein isothiocyanate-labeled casein as substrate. Oligomeric structure was evaluated by size-exclusion chromatography. The protease activities of mixtures of WT with each mutant HTRA1 were also measured. Results: Five hetero-HTRA1s had normal protease activity and were excluded from further analysis. Four of the seven hetero-HTRA1s and one of the three CARASIL-HTRA1s were unable to form trimers. The other three hetero-HTRA1s had mutations in the LD domain. Together with our previous work, 10 of 11 hetero-HTRA1s and two of six CARASIL-HTRA1s were either defective in trimerization or had mutations in the LD or L3 domain (P = 0.006). By contrast, eight of 11 hetero-HTRA1s and two of six CARASIL-HTRA1 inhibited WT protease activity (P = 0.162). Conclusions: HTRA1 mutations identified in symptomatic carriers have the property of interfering the trimer-dependent activation cascade of HTRA1.

    DOI: 10.3389/fneur.2019.00693

    PubMed

    researchmap

  • Robustness and Vulnerability of the Autoregulatory System That Maintains Nuclear TDP-43 Levels: A Trade-off Hypothesis for ALS Pathology Based on in Silico Data. Reviewed International journal

    Akihiro Sugai, Taisuke Kato, Akihide Koyama, Yuka Koike, Sou Kasahara, Takuya Konno, Tomohiko Ishihara, Osamu Onodera

    Frontiers in neuroscience   12   28 - 28   2018

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm and its disappearance from the nucleus are pathological features of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) and are directly involved in the pathogenesis of these conditions. TDP-43 is an essential nuclear protein that readily aggregates in a concentration-dependent manner. Therefore, cells must strictly maintain an appropriate amount of nuclear TDP-43. In one relevant maintenance mechanism, TDP-43 binds to its pre-mRNA and promotes alternative splicing, resulting in mRNA degradation via nonsense-mediated mRNA decay. The level of nuclear TDP-43 is tightly regulated by these mechanisms, which control the amount of mRNA that may be translated. Based on the results of previous experiments, we developed an in silico model that mimics the intracellular dynamics of TDP-43 and examined TDP-43 metabolism under various conditions. We discovered an inherent trade-off in this mechanism between transcriptional redundancy, which maintains the robustness of TDP-43 metabolism, and vulnerability to specific interfering factors. These factors include an increased tendency of TDP-43 to aggregate, impaired nuclear-cytoplasmic TDP-43 transport, and a decreased efficiency of degrading abnormal proteins, all of which are functional abnormalities related to the gene that causes familial ALS/FTD. When these conditions continue at a certain intensity, the vulnerability of the autoregulatory machinery becomes apparent over time, and transcriptional redundancy enters a vicious cycle that ultimately results in TDP-43 pathology. The results obtained using this in silico model reveal the difference in TDP-43 metabolism between normal and disease states. Furthermore, using this model, we simulated the effect of a decrease in TDP-43 transcription and found that this decrease improved TDP-43 pathology and suppressed the abnormal propagation of TDP-43. Therefore, we propose a potential therapeutic strategy to suppress transcriptional redundancy, which is the driving force of the pathological condition caused by the specific factors described above, in patients with ALS presenting with TDP-43 pathology. An ALS animal model exhibiting TDP-43 pathology without overexpression of exogenous TDP-43 should be developed to investigate the effect of alleviating the transcriptional redundancy of TARDBP.

    DOI: 10.3389/fnins.2018.00028

    PubMed

    researchmap

  • Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43 Reviewed

    Akihide Koyama, Akihiro Sugai, Taisuke Kato, Tomohiko Ishihara, Atsushi Shiga, Yasuko Toyoshima, Misaki Koyama, Takuya Konno, Sachiko Hirokawa, Akio Yokoseki, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi, Osamu Onodera

    NUCLEIC ACIDS RESEARCH   44 ( 12 )   5820 - 5836   2016.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons-especially neurons with mislocalized TDP-43-the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS.

    DOI: 10.1093/nar/gkw499

    Web of Science

    PubMed

    researchmap

  • Distinct molecular mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL. Reviewed International journal

    Hiroaki Nozaki, Taisuke Kato, Megumi Nihonmatsu, Yohei Saito, Ikuko Mizuta, Tomoko Noda, Ryoko Koike, Kazuhide Miyazaki, Muichi Kaito, Shoichi Ito, Masahiro Makino, Akihide Koyama, Atsushi Shiga, Masahiro Uemura, Yumi Sekine, Ayuka Murakami, Suzuko Moritani, Kenju Hara, Akio Yokoseki, Ryozo Kuwano, Naoto Endo, Takeshi Momotsu, Mari Yoshida, Masatoyo Nishizawa, Toshiki Mizuno, Osamu Onodera

    Neurology   86 ( 21 )   1964 - 74   2016.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: To elucidate the molecular mechanism of mutant HTRA1-dependent cerebral small vessel disease in heterozygous individuals. METHODS: We recruited 113 unrelated index patients with clinically diagnosed cerebral small vessel disease. The coding sequences of the HTRA1 gene were analyzed. We evaluated HTRA1 protease activities using casein assays and oligomeric HTRA1 formation using gel filtration chromatography. RESULTS: We found 4 heterozygous missense mutations in the HTRA1 gene (p.G283E, p.P285L, p.R302Q, and p.T319I) in 6 patients from 113 unrelated index patients and in 2 siblings in 2 unrelated families with p.R302Q. The mean age at cognitive impairment onset was 51.1 years. Spondylosis deformans was observed in all cases, whereas alopecia was observed in 3 cases; an autopsied case with p.G283E showed arteriopathy in their cerebral small arteries. These mutant HTRA1s showed markedly decreased protease activities and inhibited wild-type HTRA1 activity, whereas 2 of 3 mutant HTRA1s reported in cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (A252T and V297M) did not inhibit wild-type HTRA1 activity. Wild-type HTRA1 forms trimers; however, G283E and T319I HTRA1, observed in manifesting heterozygotes, did not form trimers. P285L and R302Q HTRA1s formed trimers, but their mutations were located in domains that are important for trimer-associated HTRA1 activation; in contrast, A252T and V297M HTRA1s, which have been observed in CARASIL, also formed trimers but had mutations outside the domains important for trimer-associated HTRA1 activation. CONCLUSIONS: The mutant HTRA1s observed in manifesting heterozygotes might result in an impaired HTRA1 activation cascade of HTRA1 or be unable to form stable trimers.

    DOI: 10.1212/WNL.0000000000002694

    PubMed

    researchmap

  • Characteristic features and progression of abnormalities on MRI for CARASIL Reviewed

    Hiroaki Nozaki, Yumi Sekine, Toshio Fukutake, Yoshinori Nishimoto, Yutaka Shimoe, Akiko Shirata, Sohei Yanagawa, Mikio Hirayama, Masato Tamura, Masatoyo Nishizawa, Osamu Onodera

    NEUROLOGY   85 ( 5 )   459 - 463   2015.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives:The objective of this study was to clarify the characteristic brain MRI findings for genetically diagnosed CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy).Methods:Seven patients with CARASIL carrying HTRA1 mutations (representing 6 Japanese families) were included in this study. Eighteen brain MRIs were reviewed and evaluated with a new rating scale based on scoring for abnormal hyperintense lesions and atrophy.Results:At the last follow-up MRI, all patients had hyperintense lesions on T2-weighted images of the frontal white matter, anterior temporal lobe, external capsules, and thalami. Patients with longer time from the onset of cognitive impairment had higher MRI severity score. The atrophy advanced, followed by white matter lesion progression. During the early stage, hyperintense lesions were observed in the frontal white matter, external capsule, and pons. During the late stage, the arc-shaped hyperintense lesion from the pons to the middle cerebellar peduncles, which we designated the arc sign, became evident. The arc sign was a characteristic finding for CARASIL in the advanced stage.Conclusions:These characteristic MRI findings for CARASIL are useful for selecting patients for genetic testing. The rating scale correlates well with disease duration and might be useful for assessing disease progression.

    DOI: 10.1212/WNL.0000000000001803

    Web of Science

    PubMed

    researchmap

  • Decreased number of Gemini of coiled bodies and U12 snRNA level in amyotrophic lateral sclerosis Reviewed

    Tomohiko Ishihara, Yuko Ariizumi, Atsushi Shiga, Taisuke Kato, Chun-Feng Tan, Tatsuya Sato, Yukari Miki, Mariko Yokoo, Takeshi Fujino, Akihide Koyama, Akio Yokoseki, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi, Osamu Onodera

    HUMAN MOLECULAR GENETICS   22 ( 20 )   4136 - 4147   2013.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Disappearance of TAR-DNA-binding protein 43 kDa (TDP-43) from the nucleus contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS), but the nuclear function of TDP-43 is not yet fully understood. TDP-43 associates with nuclear bodies including Gemini of coiled bodies (GEMs). GEMs contribute to the biogenesis of uridine-rich small nuclear RNA (U snRNA), a component of splicing machinery. The number of GEMs and a subset of U snRNAs decrease in spinal muscular atrophy, a lower motor neuron disease, suggesting that alteration of U snRNAs may also underlie the molecular pathogenesis of ALS. Here, we investigated the number of GEMs and U11/12-type small nuclear ribonucleoproteins (snRNP) by immunohistochemistry and the level of U snRNAs using real-time quantitative RT-PCR in ALS tissues. GEMs decreased in both TDP-43-depleted HeLa cells and spinal motor neurons in ALS patients. Levels of several U snRNAs decreased in TDP-43-depleted SH-SY5Y and U87-MG cells. The level of U12 snRNA was decreased in tissues affected by ALS (spinal cord, motor cortex and thalamus) but not in tissues unaffected by ALS (cerebellum, kidney and muscle). Immunohistochemical analysis revealed the decrease in U11/12-type snRNP in spinal motor neurons of ALS patients. These findings suggest that loss of TDP-43 function decreases the number of GEMs, which is followed by a disturbance of pre-mRNA splicing by the U11/U12 spliceosome in tissues affected by ALS.

    DOI: 10.1093/hmg/ddt262

    Web of Science

    PubMed

    researchmap

  • MRI Features of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Reviewed

    Hiroaki Nozaki, Yumi Sekine, Toshio Fukutake, Yoshinori Nishimoto, Mamoru Shibata, Shimoe Yutaka, Akiko Shirata, Sohei Yanagawa, Mikio Hirayama, Kiyomi Yamane, Imaharu Nakano, Norihiro Suzuki, Masatoyo Nishizawa, Osamu Onodera

    NEUROLOGY   80   560 - 566   2013.2

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminaemia Reviewed

    Akio Yokoseki, Tomohiko Ishihara, Akihide Koyama, Atsushi Shiga, Mitsunori Yamada, Chieko Suzuki, Yoshiki Sekijima, Kyoko Maruta, Miyuki Tsuchiya, Hidetoshi Date, Tatsuya Sato, Masayoshi Tada, Takeshi Ikeuchi, Shoji Tsuji, Masatoyo Nishizawa, Osamu Onodera

    BRAIN   134 ( Pt 5 )   1387 - 1399   2011.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Early onset ataxia with ocular motor apraxia and hypoalbuminaemia/ataxia-oculomotor apraxia 1 is a recessively inherited ataxia caused by mutations in the aprataxin gene. We previously reported that patients with frameshift mutations exhibit a more severe phenotype than those with missense mutations. However, reports on genotype-phenotype correlation in early onset ataxia with ocular motor apraxia and hypoalbuminaemia are controversial. To clarify this issue, we studied 58 patients from 39 Japanese families, including 40 patients homozygous for c.689_690insT and nine patients homozygous or compound heterozygous for p.Pro206Leu or p.Val263Gly mutations who were compared with regard to clinical phenotype. We performed Kaplan-Meier analysis and log-rank tests for the ages of onset of gait disturbance and the inability to walk without assistance. The cumulative rate of gait disturbance was lower among patients with p.Pro206Leu or p.Val263Gly mutations than among those homozygous for the c.689_690insT mutation (P = 0.001). The cumulative rate of inability to walk without assistance was higher in patients homozygous for the c.689_690insT mutation than in those with p.Pro206Leu or p.Val263Gly mutations (P = 0.004). Using a Cox proportional hazards model, we found that the homozygous c.689_690insT mutation was associated with an increased risk for onset of gait disturbance (adjusted hazard ratio: 6.60) and for the inability to walk without assistance (adjusted hazard ratio: 2.99). All patients homozygous for the c.689_690insT mutation presented ocular motor apraxia at < 15 years of age. Approximately half the patients homozygous for the c.689_690insT mutation developed cognitive impairment. In contrast, in the patients with p.Pro206Leu or p.Val263Gly mutations, only similar to 50% of the patients exhibited ocular motor apraxia and they never developed cognitive impairment. The stepwise multivariate regression analysis using sex, age and the number of c.689_690insT alleles as independent variables revealed that the number of c.689_690insT alleles was independently and negatively correlated with median motor nerve conduction velocities, ulnar motor nerve conduction velocities and values of serum albumin. In the patient with c.[689_690insT]+[840delT], p.[Pro206Leu]+[Pro206Leu] and p.[Pro206Leu]+[Val263Gly] mutations, aprataxin proteins were not detected by an antibody to the N-terminus of aprataxin. Furthermore Pro206Leu and Val263Gly aprataxin proteins are unstable. However, the amount of the 689_690insT aprataxin messenger RNA was also decreased, resulting in more dramatic reduction in the amount of aprataxin protein from the c.689_690insT allele. In conclusion, patients with early onset ataxia with ocular motor apraxia and hypoalbuminaemia homozygous for the c.689_690insT mutation show a more severe phenotype than those with a p.Pro206Leu or p.Val263Gly mutation.

    DOI: 10.1093/brain/awr069

    Web of Science

    PubMed

    researchmap

  • Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-beta 1 via cleavage of proTGF-beta 1 Reviewed

    Atsushi Shiga, Hiroaki Nozaki, Akio Yokoseki, Megumi Nihonmatsu, Hirotoshi Kawata, Taisuke Kato, Akihide Koyama, Kunimasa Arima, Mari Ikeda, Shinichi Katada, Yasuko Toyoshima, Hitoshi Takahashi, Akira Tanaka, Imaharu Nakano, Takeshi Ikeuchi, Masatoyo Nishizawa, Osamu Onodera

    HUMAN MOLECULAR GENETICS   20 ( 9 )   1800 - 1810   2011.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to the HTRA protein family, whose members have dual activities as chaperones and serine proteases and also repress transforming growth factor-beta (TGF-beta) family signaling. We demonstrated that CARASIL-associated mutant HTRA1s decrease protease activity and fail to decrease TGF-beta family signaling. However, the precise molecular mechanism for decreasing the signaling remains unknown. Here we show that increased expression of ED-A fibronectin is limited to cerebral small arteries and is not observed in coronary, renal arterial or aortic walls in patients with CARASIL. Using a cell-mixing assay, we found that HTRA1 decreases TGF-beta 1 signaling triggered by proTGF-beta 1 in the intracellular space. HTRA1 binds and cleaves the pro-domain of proTGF-beta 1 in the endoplasmic reticulum (ER), and cleaved proTGF-beta 1 is degraded by ER-associated degradation. Consequently, the amount of mature TGF-beta 1 is reduced. These results establish a novel mechanism for regulating the amount of TGF-proTGF-beta 1, specifically, the intracellular cleavage of proTGF-beta 1 in the ER.

    DOI: 10.1093/hmg/ddr063

    Web of Science

    PubMed

    researchmap

  • Polyglutamine Diseases: Where does Toxicity Come from? What is Toxicity? Where are We Going? Reviewed

    Toshiaki Takahashi, Shinichi Katada, Osamu Onodera

    JOURNAL OF MOLECULAR CELL BIOLOGY   2 ( 4 )   180 - 191   2010.8

     More details

    Language:English   Publisher:OXFORD UNIV PRESS  

    Although the genetic basis of polyglutamine diseases has been recognized for 20 years, their molecular basis is still unclear. We have no therapeutic strategies for these intractable neurodegenerative disorders. To adequately treat patients, we must clarify the molecular basis of polyglutamine diseases. Three main issues address their molecular pathogenesis: whether the specific structure of expanded polyglutamine diseases results in cellular toxicity; what type of dysfunction causes them; and how the toxic structure causes dysfunction, that is, the link between structure and dysfunction. For structures, expanded polyglutamine proteins undergo transformation from monomers to oligomers and inclusions. One can hypothesize that one of these structures might cause the polyglutamine disease. Although the expanded polyglutamine protein is toxic, it does not explain the selective vulnerability of specific neurons in each polyglutamine disease. The normal function of each protein, including protein-protein interaction and modification, might also be crucial for pathogenesis. For dysfunction, various molecular mechanisms have been proposed, including dysregulation of transcription, impairment of the ubiquitin-proteasome system, mitochondrial dysfunction, dysregulation of intracellular Ca2+ homeostasis, impairment of axonal transport and genotoxic stress. These hypotheses might correlate with each other. In addition, the disease pathogenesis of might not be exclusive to one particular structure or dysfunction. To develop a therapeutic strategy for patients with polyglutamine disease, identifying the most toxic structure and the earliest event in the pathogenesis is important. We review the current understanding of the toxic structure and dysfunction by expanded polyglutamine proteins and suggest directions for future studies of polyglutamine diseases.

    DOI: 10.1093/jmcb/mjq005

    Web of Science

    PubMed

    researchmap

  • Association of HTRA1 Mutations and Familial Ischemic Cerebral Small-Vessel Disease Reviewed

    Kenju Hara, Atsushi Shiga, Toshio Fukutake, Hiroaki Nozaki, Akinori Miyashita, Akio Yokoseki, Hirotoshi Kawata, Akihide Koyama, Kunimasa Arima, Toshiaki Takahashi, Mari Ikeda, Hiroshi Shiota, Masato Tamura, Yutaka Shimoe, Mikio Hirayama, Takayo Arisato, Sohei Yanagawa, Akira Tanaka, Imaharu Nakano, Shu-ichi Ikeda, Yutaka Yoshida, Tadashi Yamamoto, Takeshi Ikeuchi, Ryozo Kuwano, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    NEW ENGLAND JOURNAL OF MEDICINE   360 ( 17 )   1729 - 1739   2009.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MASSACHUSETTS MEDICAL SOC  

    BACKGROUND
    The genetic cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which is characterized by ischemic, non-hypertensive, cerebral small-vessel disease with associated alopecia and spondylosis, is unclear.
    METHODS
    In five families with CARASIL, we carried out linkage analysis, fine mapping of the region implicated in the disease, and sequence analysis of a candidate gene. We also conducted functional analysis of wild-type and mutant gene products and measured the signaling by members of the transforming growth factor beta (TGF-beta) family and gene and protein expression in the small arteries in the cerebrum of two patients with CARASIL.
    RESULTS
    We found linkage of the disease to the 2.4-Mb region on chromosome 10q, which contains the HtrA serine protease 1 (HTRA1) gene. HTRA1 is a serine protease that represses signaling by TGF-beta family members. Sequence analysis revealed two nonsense mutations and two missense mutations in HTRA1. The missense mutations and one of the nonsense mutations resulted in protein products that had comparatively low levels of protease activity and did not repress signaling by the TGF-beta family. The other nonsense mutation resulted in the loss of HTRA1 protein by nonsense-mediated decay of messenger RNA. Immunohistochemical analysis of the cerebral small arteries in affected persons showed increased expression of the extra domain-A region of fibronectin and versican in the thickened tunica intima and of TGF-beta 1 in the tunica media.
    CONCLUSIONS
    CARASIL is associated with mutations in the HTRA1 gene. Our findings indicate a link between repressed inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.

    DOI: 10.1056/NEJMoa0801560

    Web of Science

    PubMed

    researchmap

  • TDP-43 mutation in familial amyotrophic lateral sclerosis Reviewed

    Akio Yokoseki, Atsushi Shiga, Chun-Feng Tan, Asako Tagawa, Hiroyuki Kaneko, Akihide Koyama, Hiroto Eguchi, Akira Tsujino, Takeshi Ikeuchi, Akiyoshi Kakita, Koichi Okamoto, Masatoyo Nishizava, Hitoshi Takahashi, Osamu Onodera

    ANNALS OF NEUROLOGY   63 ( 4 )   538 - 542   2008.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these findings are indistinguishable from those of sporadic ALS. In three affected individuals in two generations of one family, we found a single base-pair change from A to G at position 1028 in TDP-43, which resulted in a Gln-to-Arg substitution at position 343. Our findings provide a new insight into the molecular pathogenesis of ALS.

    DOI: 10.1002/ana.21392

    Web of Science

    PubMed

    researchmap

  • Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic Reviewed

    Toshiaki Takahashi, Shinya Kikuchi, Shinichi Katada, Yoshitaka Nagai, Masatoyo Nishizawa, Osamu Onodera

    HUMAN MOLECULAR GENETICS   17 ( 3 )   345 - 356   2008.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Expanded polyglutamine (polyQ) repeats cause neurodegenerative disorders, but their cytotoxic structures remain to be elucidated. Although soluble polyQ oligomers have been proposed as a cytotoxic structure, the cytotoxicity of soluble polyQ oligomers, not inclusion bodies (IBs), has not been proven in living cells. To clarify the cytotoxicity of soluble polyQ oligomers, we carried our fluorescence resonance energy transfer (FRET) confocal microscopy and distinguished oligomers from monomers and IBs in a single living cell. FRET signals were detected when donor and acceptor fluorescent proteins were attached to the same side, not the opposite side, of polyQ repeats, which agrees with a parallel beta-sheet or a head-to-tail cylindrical beta-sheet model. These FRET signals disappeared in semi-intact cells, indicating that these polyQ oligomers are soluble. PolyQ monomers assembled into soluble oligomers in a length-dependent manner, which was followed by the formation of IBs. Notably, survival assay of neuronally differentiated cells revealed that cells with soluble oligomers died faster than those with IBs or monomers. These results indicate that a length-dependent formation of oligomers is an essential mechanism underlying neurodegeneration in polyQ-mediated disorders.

    DOI: 10.1093/hmg/ddm311

    Web of Science

    PubMed

    researchmap

  • Aprataxin, causative gene product for EAOH/AOA1, repairs DNA single-strand breaks with damaged 3 '-phosphate and 3 '-phosphoglycolate ends Reviewed

    Tetsuya Takahashi, Masayoshi Tada, Shuichi Igarashi, Akihide Koyama, Hidetoshi Date, Akio Yokoseki, Atsushi Shiga, Yutaka Yoshida, Shoji Tsuji, Masatoyo Nishizawa, Osamu Onodera

    NUCLEIC ACIDS RESEARCH   35 ( 11 )   3797 - 3809   2007.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Aprataxin is the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ ataxia with oculomotor apraxia type 1 (EAOH/AOA1), the clinical symptoms of which are predominantly neurological. Although aprataxin has been suggested to be related to DNA single-strand break repair (SSBR), the physiological function of aprataxin remains to be elucidated. DNA single-strand breaks (SSBs) continually produced by endogenous reactive oxygen species or exogenous genotoxic agents, typically possess damaged 3'-ends including 3'-phosphate, 3'-phosphoglycolate, or 3'-alpha, beta-unsaturated aldehyde ends. These damaged 3'-ends should be restored to 3'-hydroxyl ends for subsequent repair processes. Here we demonstrate by in vitro assay that recombinant human aprataxin specifically removes 3'-phosphoglycolate and 3'-phosphate ends at DNA 3'-ends, but not 3'-alpha, beta-unsaturated aldehyde ends, and can act with DNA polymerase beta and DNA ligase III to repair SSBs with these damaged 3'-ends. Furthermore, disease-associated mutant forms of aprataxin lack this removal activity. The findings indicate that aprataxin has an important role in SSBR, that is, it removes blocking molecules from 3'-ends, and that the accumulation of unrepaired SSBs with damaged 3'-ends underlies the pathogenesis of EAOH/AOA1. The findings will provide new insight into the mechanism underlying degeneration and DNA repair in neurons.

    DOI: 10.1093/nar/gkm158

    Web of Science

    PubMed

    researchmap

  • Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy Reviewed

    Mari Tada, Osamu Onodera, Masayoshi Tada, Tetsutaro Ozawa, Yue-Shan Piao, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa

    ARCHIVES OF NEUROLOGY   64 ( 2 )   256 - 260   2007.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: Multiple system atrophy (MSA) is diverse in clinical phenotype, disease progression, and prognosis. Sudden death is a leading cause of death in patients with MSA.
    Objective: To determine what clinical factors affect the progression and survival prognosis of those with MSA.
    Design: A retrospective review of the medical records of 49 consecutive Japanese patients with pathologically confirmed MSA ( 29 men and 20 women; mean +/- SD age at onset, 59.8 +/- 6.5 years). Cox proportional hazards models were used to compare the risks of being in a wheel-chair-bound state, being in a bedridden state, and having a shorter survival.
    Results: Thirty-one patients were diagnosed as having cerebellar type MSA, and 18 were diagnosed as having parkinsonian type MSA. Twenty-nine patients with cerebellar type MSA and 17 patients with parkinsonian type MSA had autonomic dysfunction. The median times from disease onset to being in a wheel-chair-bound state, being in a bedridden state, death, and the development of autonomic dysfunction were 3.5, 5.0, 7.0, and 2.5 years, respectively. Patients with an early development of autonomic dysfunction (within 2.5 years from the onset of MSA) had significantly higher risks of being in a wheel-chair-bound state (multivariate-adjusted hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.04-9.15), being in a bedridden state (HR, 3.87; 95% CI, 1.77-8.48), having a shorter survival (HR, 3.40; 95% CI, 1.61-7.15), and sudden death (HR, 7.22; 95% CI, 1.49-35.07).
    Conclusion: The early development of autonomic dysfunction is an independent predictive factor for rapid disease progression and shorter survival in patients with MSA.

    DOI: 10.1001/archneur.64.2.256

    Web of Science

    PubMed

    researchmap

  • Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene Reviewed

    H Date, O Onodera, H Tanaka, K Iwabuchi, K Uekawa, S Igarashi, R Koike, T Hiroi, T Yuasa, Y Awaya, T Sakai, T Takahashi, H Nagatomo, Y Sekijima, Kawachi, I, Y Takiyama, M Nishizawa, N Fukuhara, K Saito, S Sugano, S Tsuji

    NATURE GENETICS   29 ( 2 )   184 - 188   2001.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE AMERICA INC  

    Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs(1-4). We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus(5). We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.

    DOI: 10.1038/ng1001-184

    Web of Science

    PubMed

    researchmap

  • Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado-Joseph disease Reviewed

    O Onodera, J Idezuka, S Igarashi, Y Takiyama, K Endo, H Takano, M Oyake, H Tanaka, T Inuzuka, T Hayashi, T Yuasa, J Ito, T Miyatake, S Tsuji

    ANNALS OF NEUROLOGY   43 ( 3 )   288 - 296   1998.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia associated to varying degrees with pyramidal signs, extrapyramidal signs, or peripheral amyotrophy. It is caused by unstable expansion of the CAG repeat in the MJD1 gene on chromosome 14q32.1. To determine how the neurodegenerative process in the central nervous system of patients with MJD correlates with the size of expanded CAG repeats in the MJD1 gene and other factors, we performed detailed quantitative analyses of findings of magnetic resonance imaging of the central nervous system of 21 patients with MJD of various ages and with various sizes of expanded CAG repeats. We found that atrophy of the brainstem and cerebellar vermis in MJD patients is closely correlated not only with the size of expanded CAG repeat in the MJD1 gene but also with patient age, which suggests that the neurodegenerative process in MJD is regulated by the size of expanded CAG repeats as well as by the patient age.

    DOI: 10.1002/ana.410430305

    Web of Science

    PubMed

    researchmap

  • Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy: Cellular population-dependent dynamics of mitotic instability Reviewed

    H Takano, O Onodera, H Takahashi, S Igarashi, M Yamada, M Oyake, T Ikeuci, R Koide, H Tanaka, K Iwabuchi, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   58 ( 6 )   1212 - 1222   1996.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:UNIV CHICAGO PRESS  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG repeat in the DRPLA gene. We performed detailed quantitative analysis of the size and the size distribution (range) of the expanded CAG repeats in various regions of the CNS of eight autopsied patients with DRPLA. Expanded alleles (AE) showed considerable variations in size, as well as in range, depending on the region of the CNS, whereas normal alleles did not show such variations, which indicates the occurrence of somatic mosaicism of AE in the CNS. The AE in the cerebellar cortex were consistently smaller by two to five repeat units than those in the cerebellar white matter. Moreover, the AE in the cerebral cortex were smaller by one to four repeat units than those in the cerebral white matter. These results suggest that the smaller AE in the cerebellar and cerebral cortices represent those of neuronal cells. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter showed considerable variation ranging from 9 to 23 repeat units, whereas those in the cerebellar cortex showed little variance and were similar to 7 repeat units. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter were much broader in patients with higher ages at death than they were in patients with lower ages at death, raising the possibility that the range of AE increases with time, as the result of mitotic instability of AE.

    Web of Science

    PubMed

    researchmap

  • MOLECULAR-CLONING OF A FULL-LENGTH CDNA FOR DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY AND REGIONAL EXPRESSIONS OF THE EXPANDED ALLELES IN THE CNS Reviewed

    O ONODERA, M OYAKE, H TAKANO, T IKEUCHI, S IGARASHI, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   57 ( 5 )   1050 - 1060   1995.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:UNIV CHICAGO PRESS  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by genetic anticipation and variable combinations of symptoms including myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Recently, we discovered that DRPLA is caused by unstable expansion of a CAG repeat of a gene on the short arm of chromosome 12. We determined the consensus DRPLA cDNA sequence containing the complete coding region for 1,185 amino acids. The CAG repeat, which is expanded in DRPLA, is located 1,462 bp downstream from the putative methionine initiation codon and encodes a poly-glutamine tract. Although poly-serine and proline tracts exist near the CAG repeats, these polyserine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat. Northern blot analysis revealed a 4.7-kb transcript that is widely expressed in various tissues including heart, lung, kidney, placenta, skeletal muscle, and brain. Reverse transcription-PCR analysis revealed that the expanded alleles are transcribed to levels comparable to those of normal alleles. These results indicate that there is no difference in transcriptional efficiency between expanded and normal alleles. Furthermore, mRNA from cerebellar hemispheres of DRPLA patients showed smaller sizes of CAG repeats compared with other regions of the brain, which reflects somatic mosaicism of the expanded alleles of the DRPLA gene.

    Web of Science

    PubMed

    researchmap

  • GENETIC ASSOCIATION OF THE VERY-LOW-DENSITY LIPOPROTEIN (VLDL) RECEPTOR GENE WITH SPORADIC ALZHEIMERS-DISEASE Reviewed

    K OKUIZUMI, O ONODERA, Y NAMBA, K IKEDA, T YAMAMOTO, K SEKI, A UEKI, S NANKO, H TANAKA, H TAKAHASHI, K OYANAGI, H MIZUSAWA, KANAZAWA, I, S TSUJI

    NATURE GENETICS   11 ( 2 )   207 - 209   1995.10

     More details

    Language:English   Publisher:NATURE PUBLISHING CO  

    DOI: 10.1038/ng1095-207

    Web of Science

    PubMed

    researchmap

  • UNSTABLE EXPANSION OF CAG REPEAT IN HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) Reviewed

    R KOIDE, T IKEUCHI, O ONODERA, H TANAKA, S IGARASHI, K ENDO, H TAKAHASHI, R KONDO, A ISHIKAWA, T HAYASHI, M SAITO, A TOMODA, T MIIKE, H NAITO, F IKUTA, S TSUJI

    NATURE GENETICS   6 ( 1 )   9 - 13   1994.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING CO  

    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22 DRPLA patients examined. A good correlation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tended to have a phenotype of progressive myoclonus epilepsy and larger expansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of the CAG repeat.

    DOI: 10.1038/ng0194-9

    Web of Science

    PubMed

    researchmap

  • Cerebellar compensation: a case of aphasia due to cerebellar hemorrhage

    Yukiko Kinoshita, Masahiro Hatakeyama, Mika Otsuki, Takanobu Ishiguro, Etsuji Saji, Masato Kanazawa, Osamu Onodera

    Journal of Neurology   2024.3

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00415-024-12276-6

    researchmap

  • Dysregulation of stress granule dynamics by DCTN1 deficiency exacerbates TDP-43 pathology in Drosophila models of ALS/FTD

    Tetsuhiro Ueda, Toshihide Takeuchi, Nobuhiro Fujikake, Mari Suzuki, Eiko N. Minakawa, Morio Ueyama, Yuzo Fujino, Nobuyuki Kimura, Seiichi Nagano, Akio Yokoseki, Osamu Onodera, Hideki Mochizuki, Toshiki Mizuno, Keiji Wada, Yoshitaka Nagai

    Acta Neuropathologica Communications   12 ( 1 )   2024.2

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo. We demonstrated using a Drosophila model of ALS/FTD that genetic knockdown of DCTN1 accelerates the formation of ubiquitin-positive cytoplasmic inclusions of TDP-43. Knockdown of components of other microtubule-associated motor protein complexes, including dynein and kinesin, also increased the formation of TDP-43 inclusions, indicating that intracellular transport along microtubules plays a key role in TDP-43 pathology. Notably, DCTN1 knockdown delayed the disassembly of stress granules in stressed cells, leading to an increase in the formation of pathological cytoplasmic inclusions of TDP-43. Our results indicate that a deficiency in DCTN1, as well as disruption of intracellular transport along microtubules, is a modifier that drives the formation of TDP-43 pathology through the dysregulation of stress granule dynamics.

    DOI: 10.1186/s40478-024-01729-8

    researchmap

    Other Link: https://link.springer.com/article/10.1186/s40478-024-01729-8/fulltext.html

  • Validation study of the Japanese version of the King's Parkinson's Disease Pain Scale and the King's Parkinson's Disease Pain Questionnaire. International journal

    Kanako Kurihara, Shinsuke Fujioka, Yasuaki Mizutani, Hirohisa Watanabe, Kazuhiro Iwaoka, Tetsuya Maeda, Morinobu Seki, Toshiki Tezuka, Jin Nakahara, Takuya Konno, Takanobu Ishiguro, Osamu Onodera, Yuri Asano, Kazushi Takahashi, Alexandra Rizos, K Ray Chaudhuri, Yoshio Tsuboi

    Parkinsonism & related disorders   120   106012 - 106012   2024.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    INTRODUCTION: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. METHODS: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. RESULTS: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562-0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617-0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0-1.0). CONCLUSIONS: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.

    DOI: 10.1016/j.parkreldis.2024.106012

    PubMed

    researchmap

  • Clinicopathologic features of two unrelated autopsied patients with Charcot-Marie-Tooth disease carrying MFN2 gene mutation. International journal

    Hideki Hayashi, Rie Saito, Hidetomo Tanaka, Norikazu Hara, Shin Koide, Yosuke Yonemochi, Tetsuo Ozawa, Mariko Hokari, Yasuko Toyoshima, Akinori Miyashita, Osamu Onodera, Kouichirou Okamoto, Takeshi Ikeuchi, Takashi Nakajima, Akiyoshi Kakita

    Acta neuropathologica communications   11 ( 1 )   207 - 207   2023.12

     More details

  • Missense Variants in COL4A1/2 Are Associated with Cerebral Aneurysms: A Case Report and <span aria-describedby="tippy-31">Literature Review

    Masahiro Uemura, Natsuki Tanaka, Shoichiro Ando, Takehiko Yanagihara, Osamu Onodera

    Neurology International   2023.12

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.20944/preprints202312.1336.v1

    researchmap

  • Neuroprotective effects of oral metformin before stroke on cerebral small-vessel disease. International journal

    Natsuki Akiyama, Takayuki Yamashiro, Itaru Ninomiya, Masahiro Uemura, Yorito Hattori, Masafumi Ihara, Osamu Onodera, Masato Kanazawa

    Journal of the neurological sciences   456   122812 - 122812   2023.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Metformin (MET) treatment prior to stroke might have neuroprotective effects other than hypoglycemic effects. This study evaluated whether MET treatment prior to stroke is associated with neurological severity and functional outcome in patients with stroke who were not indicated for endovascular treatment and whether the effects of MET differ for each ischemic stroke subtype. METHODS: We investigated 160 type 2 diabetes mellitus patients with ischemic stroke without endovascular treatment who were taking some oral antidiabetic agents prior to stroke in two tertiary hospitals. Lower neurological severity was defined as a National Institutes of Health Stroke Scale score of 3 or lower on admission, and favorable functional outcome was defined as a modified Rankin Scale score = 0-2 at discharge. We analyzed the effects of MET on the neurological severity and functional outcome in each ischemic stroke subtype on logistic regression analysis with adjustments for multiple confounding factors. RESULTS: MET treatment prior to stroke was associated with lower stroke severity and favorable functional outcome. In the stroke subtypes, MET use affected both neurological severity (P = 0.037) and functional outcome (P = 0.041) in only patients with small-vessel disease (SVD). CONCLUSIONS: MET may be useful to improve the outcome of patients with SVD.

    DOI: 10.1016/j.jns.2023.122812

    PubMed

    researchmap

  • Marked laterality of olivopontocerebellar pathology in an autopsied patient with MSA: Implications for degeneration and α-synuclein propagation. International journal

    Misato Ozawa, Rie Saito, Takuya Konno, Reiji Koide, Shigeru Fujimoto, Osamu Onodera, Akiyoshi Kakita

    Journal of neurology, neurosurgery, and psychiatry   2023.11

     More details

  • A case report of reversible cerebral vasoconstriction syndrome with thunderclap headache significantly exacerbated in the supine position and alleviated in the standing position. International journal

    Genri Toyama, Shintaro Tsuboguchi, Kazuya Igarashi, Etsuji Saji, Takuya Konno, Osamu Onodera

    BMC neurology   23 ( 1 )   348 - 348   2023.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden onset thunderclap headache and multiple segmental reversible cerebral vasoconstrictions that improve within 3 months. The postpartum period is a well-known precipitating factor for the onset of RCVS. Cerebral venous thrombosis (CVT) causes thunderclap headaches in the postpartum period. While headache in CVT is sometimes exacerbated in the supine position, the severity of the headache in RCVS is usually independent of body position. In this study, we report a case of RCVS with thunderclap headache exacerbated in the supine position, and headache attacks that resolved quickly in the standing position during the postpartum period. CASE PRESENTATION: A 33-year-old woman presented with a sudden increase in blood pressure and thunderclap headache on the fifth postpartum day (day 1: the first sick day). The headache was severe and pulsatile, with onset in the supine position in bed, and peaked at approximately 10 s. It was accompanied by nausea and chills but there were no scintillating scotomas or ophthalmic symptoms. The headache resolved in the standing or sitting position but was exacerbated and became unbearable within a few seconds when the patient was in the supine position. Therefore, she was unable to lie supine at night. Computed tomography angiography (CTA) of the head on day 2 and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) on day 3 showed no abnormalities. However, considering the possibility of RCVS, verapamil was initiated on day 3. The headache resolved the following day. MRA of the head on day 10 revealed diffuse and segmental stenoses in the bilateral middle and posterior cerebral arteries and basilar artery. Therefore, the patient was diagnosed with RCVS. The headache gradually resolved and disappeared completely on day 42. Cerebral vasoconstriction was also improved on MRA on day 43. CONCLUSIONS: This postpartum RCVS case was notable for the exacerbation of headaches in the supine position. For the diagnosis of thunderclap headache in the postpartum period, RCVS should be considered in addition to CVT when the patient presents with a headache that is exacerbated in the supine position.

    DOI: 10.1186/s12883-023-03381-6

    PubMed

    researchmap

  • 発作性の神経症状を繰り返し、多発する微小出血像を認めた硬膜移植歴を有する39歳男性例

    畠山 祐樹, 坪口 晋太朗, 石黒 敬信, 佐治 越爾, 畠山 公大, 島田 斉, 金澤 雅人, 小野寺 理

    臨床神経学   63 ( 9 )   603 - 603   2023.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • SCA6の浸透性に関する研究(Study of penetrance of SCA6)

    Hatano Yuya, Ishihara Tomohiko, Hirokawa Sachiko, Onodera Osamu

    臨床神経学   63 ( Suppl. )   S335 - S335   2023.9

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • 脳梗塞発症前のメトホルミン内服による脳小血管病に対する神経保護効果

    秋山 夏葵, 二宮 格, 山城 貴之, 上村 昌寛, 服部 頼都, 猪原 匡史, 小野寺 理, 金澤 雅人

    臨床神経学   63 ( Suppl. )   S310 - S310   2023.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD. International journal

    Yuzo Fujino, Morio Ueyama, Taro Ishiguro, Daisaku Ozawa, Hayato Ito, Toshihiko Sugiki, Asako Murata, Akira Ishiguro, Tania Gendron, Kohji Mori, Eiichi Tokuda, Tomoya Taminato, Takuya Konno, Akihide Koyama, Yuya Kawabe, Toshihide Takeuchi, Yoshiaki Furukawa, Toshimichi Fujiwara, Manabu Ikeda, Toshiki Mizuno, Hideki Mochizuki, Hidehiro Mizusawa, Keiji Wada, Kinya Ishikawa, Osamu Onodera, Kazuhiko Nakatani, Leonard Petrucelli, Hideki Taguchi, Yoshitaka Nagai

    eLife   12   2023.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.

    DOI: 10.7554/eLife.84338

    PubMed

    researchmap

  • Inappropriate interpretation of non-pathogenic HTRA1 variant as pathogenic. International journal

    Masahiro Uemura, Sho Kitahara, Taisuke Kato, Hiroaki Nozaki, Shoichiro Ando, Tomohiko Ishihara, Osamu Onodera

    Annals of clinical and translational neurology   10 ( 7 )   1261 - 1262   2023.7

     More details

  • The clinical application of optimized AT(N) classification in Alzheimer’s clinical syndrome (ACS) and non-ACS conditions

    Kensaku Kasuga, Tamao Tsukie, Masataka Kikuchi, Takayoshi Tokutake, Kazuo Washiyama, Soichiro Shimizu, Hiroshi Yoshizawa, Yasuko Kuroha, Ryuji Yajima, Hiroshi Mori, Yasuaki Arakawa, Kiyoshi Onda, Akinori Miyashita, Osamu Onodera, Takeshi Iwatsubo, Takeshi Ikeuchi

    Neurobiology of Aging   127   23 - 32   2023.7

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.neurobiolaging.2023.03.007

    researchmap

  • [Disseminated herpes zoster complicated by lumbosacral polyradiculoneuritis and fibular neuropathy: A case report].

    Kosei Nakamura, Shintaro Tsuboguchi, Itaru Ninomiya, Osamu Ansai, Masato Kanazawa, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   63 ( 6 )   359 - 362   2023.6

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A 74-year-old woman who presented with a skin eruption involving the left lateral leg along the L5 dermatome and widespread eruptions on the buttocks and trunk was diagnosed with disseminated herpes zoster (HZ). She also had left lower extremity muscle weakness. The pattern of distribution of muscle weakness and gadolinium-enhanced magnetic resonance imaging findings indicated polyradiculoneuritis mainly affecting the L5 spinal root. Moreover, we observed severe weakness of the left tibialis anterior muscle. Weakness of the other L5 myotomes reduced after antiviral treatment; however, left tibialis anterior muscle weakness persisted. We concluded that lumbosacral polyradiculoneuritis was attributable to varicella-zoster virus (VZV) infection, which also caused fibular neuropathy in this case. Retrograde transport of the VZV may have infected the fibular nerve throughout the sites of skin eruption. It is important to be mindful of simultaneous nerve root and peripheral nerve involvement in cases of motor paralysis associated with HZ infection.

    DOI: 10.5692/clinicalneurol.cn-001848

    PubMed

    researchmap

  • Progressive conus medullaris lesions are suggestive of intravascular large B-cell lymphoma. International journal

    Sho Kitahara, Masato Kanazawa, Manabu Natsumeda, Aki Sato, Masanori Ishikawa, Kenju Hara, Hiroyuki Tabe, Kunihiko Makino, Kouichirou Okamoto, Nobuya Fujita, Akiyoshi Kakita, Yukihiko Fuji, Osamu Onodera

    European journal of neurology   2023.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND AND PURPOSE: Spinal cord lesions are observed in 40% of all central nervous system lesions in intravascular large B-cell lymphoma (IVLBCL). However, because IVLBCL is a very rare disease, its clinical features are not well defined, which may delay appropriate diagnosis and treatment, whilst the acute to subacute course of brain lesions in patients with IVLBCL is well established. Therefore, this study aimed to clarify the clinical features of spinal cord lesions in patients with IVLBCL. METHODS: The medical records of patients with IVLBCL admitted to our hospital between 2010 and 2020 were searched. The inclusion criteria were preceding neurological symptoms without non-neurological symptoms and pathologically confirmed IVLBCL in various organs. Clinical features of spinal cord involvement in patients with IVLBCL were assessed and distinguished from those of brain involvement. RESULTS: Sixteen consecutive patients with IVLBCL were divided into two groups: six patients with spinal involvement (spinal cord type) and 10 patients with brain involvement (brain type). In the spinal cord type, four patients had chronic progression and two had subacute progression. Acute progression (0% vs. 80.0%) and sudden onset (0% vs. 50.0%) occurred significantly less frequently in the spinal cord than in the brain. All spinal cord lesions involved the conus medullaris. CONCLUSIONS: Spinal cord involvement in IVLBCL has a predominantly chronic progressive course that is exclusive to brain involvement. Conus medullaris lesions are suggestive of IVLBCL and are useful for early and accurate diagnosis and treatment.

    DOI: 10.1111/ene.15941

    PubMed

    researchmap

  • Oxygen–Glucose Deprived Peripheral Blood Mononuclear Cells Protect Against Ischemic Stroke

    Yutaka Otsu, Masahiro Hatakeyama, Takeshi Kanayama, Natsuki Akiyama, Itaru Ninomiya, Kaoru Omae, Taisuke Kato, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata, Masato Kanazawa

    Neurotherapeutics   2023.6

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s13311-023-01398-w

    researchmap

    Other Link: https://link.springer.com/article/10.1007/s13311-023-01398-w/fulltext.html

  • Preclinical Characterization of the Tau PET Tracer [<sup>18</sup>F]SNFT-1: Comparison of Tau PET Tracers Reviewed

    Ryuichi Harada, Pradith Lerdsirisuk, Yuki Shimizu, Yuka Yokoyama, Yiqing Du, Kaede Kudo, Michinori Ezura, Yoichi Ishikawa, Ren Iwata, Miho Shidahara, Aiko Ishiki, Akio Kikuchi, Yuya Hatano, Tomohiko Ishihara, Osamu Onodera, Yasushi Iwasaki, Mari Yoshida, Yasuyuki Taki, Hiroyuki Arai, Yukitsuka Kudo, Kazuhiko Yanai, Shozo Furumoto, Nobuyuki Okamura

    Journal of Nuclear Medicine   jnumed.123.265593 - jnumed.123.265593   2023.6

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Society of Nuclear Medicine  

    DOI: 10.2967/jnumed.123.265593

    researchmap

  • Heterogenous Genetic, Clinical, and Imaging Features in Patients with Neuronal Intranuclear Inclusion Disease Carrying NOTCH2NLC Repeat Expansion. International journal

    Yusran Ady Fitrah, Yo Higuchi, Norikazu Hara, Takayoshi Tokutake, Masato Kanazawa, Kazuhiro Sanpei, Tomone Taneda, Akihiko Nakajima, Shin Koide, Shintaro Tsuboguchi, Midori Watanabe, Junki Fukumoto, Shoichiro Ando, Tomoe Sato, Yohei Iwafuchi, Aki Sato, Hideki Hayashi, Takanobu Ishiguro, Hayato Takeda, Toshiaki Takahashi, Nobuyoshi Fukuhara, Kensaku Kasuga, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi

    Brain sciences   13 ( 6 )   2023.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder that is caused by the abnormal expansion of non-coding trinucleotide GGC repeats in NOTCH2NLC. NIID is clinically characterized by a broad spectrum of clinical presentations. To date, the relationship between expanded repeat lengths and clinical phenotype in patients with NIID remains unclear. Thus, we aimed to clarify the genetic and clinical spectrum and their association in patients with NIID. For this purpose, we genetically analyzed Japanese patients with adult-onset NIID with characteristic clinical and neuroimaging findings. Trinucleotide repeat expansions of NOTCH2NLC were examined by repeat-primed and amplicon-length PCR. In addition, long-read sequencing was performed to determine repeat size and sequence. The expanded GGC repeats ranging from 94 to 361 in NOTCH2NLC were found in all 15 patients. Two patients carried biallelic repeat expansions. There were marked heterogenous clinical and imaging features in NIID patients. Patients presenting with cerebellar ataxia or urinary dysfunction had a significantly larger GGC repeat size than those without. This significant association disappeared when these parameters were compared with the total trinucleotide repeat number. ARWMC score was significantly higher in patients who had a non-glycine-type trinucleotide interruption within expanded poly-glycine motifs than in those with a pure poly-glycine expansion. These results suggested that the repeat length and sequence in NOTCH2NLC may partly modify some clinical and imaging features of NIID.

    DOI: 10.3390/brainsci13060955

    PubMed

    researchmap

  • Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution. International journal

    Priya Jagota, Yoshikazu Ugawa, Zakiyah Aldaajani, Norlinah Mohamed Ibrahim, Hiroyuki Ishiura, Yoshiko Nomura, Shoji Tsuji, Cid Diesta, Nobutaka Hattori, Osamu Onodera, Saeed Bohlega, Amir S N AlDin, Shen-Yang Lim, Jee-Young Lee, Beomseok Jeon, Pramod Kumar Pal, Huifang Shang, Shinsuke Fujioka, Prashanth Lingappa Kukkle, Onanong Phokaewvarangkul, Chin-Hsien Lin, Cholpon Shambetova, Roongroj Bhidayasiri

    Journal of movement disorders   2023.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia - Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism (XDP), dentatorubral-pallidoluysian atrophy (DRPLA), Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy (BAFME), Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 (CAMTA2) gene, and paroxysmal kinesigenic dyskinesia (PKD). We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

    DOI: 10.14802/jmd.23065

    PubMed

    researchmap

  • Accuracy of a machine learning method based on structural and locational information from AlphaFold2 for predicting the pathogenicity of TARDBP and FUS gene variants in ALS

    Yuya Hatano, Tomohiko Ishihara, Osamu Onodera

    BMC Bioinformatics   24 ( 1 )   2023.5

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Background

    In the sporadic form of amyotrophic lateral sclerosis (ALS), the pathogenicity of rare variants in the causative genes characterizing the familial form remains largely unknown. To predict the pathogenicity of such variants, in silico analysis is commonly used. In some ALS causative genes, the pathogenic variants are concentrated in specific regions, and the resulting alterations in protein structure are thought to significantly affect pathogenicity. However, existing methods have not taken this issue into account. To address this, we have developed a technique termed MOVA (method for evaluating the pathogenicity of missense variants using AlphaFold2), which applies positional information for structural variants predicted by AlphaFold2. Here we examined the utility of MOVA for analysis of several causative genes of ALS.

    Methods

    We analyzed variants of 12 ALS-related genes (TARDBP, FUS, SETX, TBK1, OPTN, SOD1, VCP, SQSTM1, ANG, UBQLN2, DCTN1, and CCNF) and classified them as pathogenic or neutral. For each gene, the features of the variants, consisting of their positions in the 3D structure predicted by AlphaFold2, pLDDT score, and BLOSUM62 were trained into a random forest and evaluated by the stratified fivefold cross validation method. We compared how accurately MOVA predicted mutant pathogenicity with other in silico prediction methods and evaluated the prediction accuracy at TARDBP and FUS hotspots. We also examined which of the MOVA features had the greatest impact on pathogenicity discrimination.

    Results

    MOVA yielded useful results (AUC ≥ 0.70) for TARDBP, FUS, SOD1, VCP, and UBQLN2 of 12 ALS causative genes. In addition, when comparing the prediction accuracy with other in silico prediction methods, MOVA obtained the best results among those compared for TARDBP, VCP, UBQLN2, and CCNF. MOVA demonstrated superior predictive accuracy for the pathogenicity of mutations at hotspots of TARDBP and FUS. Moreover, higher accuracy was achieved by combining MOVA with REVEL or CADD. Among the features of MOVA, the x, y, and z coordinates performed the best and were highly correlated with MOVA.

    Conclusions

    MOVA is useful for predicting the virulence of rare variants in which they are concentrated at specific structural sites, and for use in combination with other prediction methods.

    DOI: 10.1186/s12859-023-05338-5

    researchmap

    Other Link: https://link.springer.com/article/10.1186/s12859-023-05338-5/fulltext.html

  • V180I genetic Creutzfeldt-Jakob disease: Severe degeneration of the inferior olivary nucleus in an autopsied patient with identification of the M2T prion strain. International journal

    Midori Watanabe, Kosei Nakamura, Rie Saito, Atsuko Takeuchi, Tetsuya Takahashi, Tetsuyuki Kitamoto, Osamu Onodera, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   2023.5

     More details

    Language:English  

    Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81-year-old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic-type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD-MM2T but preserved in other patients with V180I gCJD and sCJD-MM1 (this patient, 2.3 ± 0.53/mm2 ; a patient with sCJD-MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD-MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here.

    DOI: 10.1111/neup.12908

    PubMed

    researchmap

  • Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and verification in iPSC-derived motor neurons from patients. International journal

    Ryoichi Nakamura, Genki Tohnai, Masahiro Nakatochi, Naoki Atsuta, Hirohisa Watanabe, Daisuke Ito, Masahisa Katsuno, Akihiro Hirakawa, Yuishin Izumi, Mitsuya Morita, Takehisa Hirayama, Osamu Kano, Kazuaki Kanai, Nobutaka Hattori, Akira Taniguchi, Naoki Suzuki, Masashi Aoki, Ikuko Iwata, Ichiro Yabe, Kazumoto Shibuya, Satoshi Kuwabara, Masaya Oda, Rina Hashimoto, Ikuko Aiba, Tomohiko Ishihara, Osamu Onodera, Toru Yamashita, Koji Abe, Kouichi Mizoguchi, Toshio Shimizu, Yoshio Ikeda, Takanori Yokota, Kazuko Hasegawa, Fumiaki Tanaka, Kenji Nakashima, Ryuji Kaji, Jun-Ichi Niwa, Manabu Doyu, Chikashi Terao, Shiro Ikegawa, Koki Fujimori, Shiho Nakamura, Fumiko Ozawa, Satoru Morimoto, Kazunari Onodera, Takuji Ito, Yohei Okada, Hideyuki Okano, Gen Sobue

    Journal of neurology, neurosurgery, and psychiatry   94 ( 10 )   816 - 824   2023.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS. METHODS: We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants. We used Cox proportional hazards regression analysis with an additive model adjusted for sex, age at onset and the first two principal components calculated from genotyped data to conduct a genome-wide association study. We further analysed messenger RNA (mRNA) and phenotype expression in motor neurons derived from induced pluripotent stem cells (iPSC-MNs) of patients with ALS. RESULTS: Three novel loci were significantly associated with the survival of patients with sporadic ALS-FGF1 at 5q31.3 (rs11738209, HR=2.36 (95% CI, 1.77 to 3.15), p=4.85×10-9), THSD7A at 7p21.3 (rs2354952, 1.38 (95% CI, 1.24 to 1.55), p=1.61×10-8) and LRP1 at 12q13.3 (rs60565245, 2.18 (95% CI, 1.66 to 2.86), p=2.35×10-8). FGF1 and THSD7A variants were associated with decreased mRNA expression of each gene in iPSC-MNs and reduced in vitro survival of iPSC-MNs obtained from patients with ALS. The iPSC-MN in vitro survival was reduced when the expression of FGF1 and THSD7A was partially disrupted. The rs60565245 was not associated with LRP1 mRNA expression. CONCLUSIONS: We identified three loci associated with the survival of patients with sporadic ALS, decreased mRNA expression of FGF1 and THSD7A and the viability of iPSC-MNs from patients. The iPSC-MN model reflects the association between patient prognosis and genotype and can contribute to target screening and validation for therapeutic intervention.

    DOI: 10.1136/jnnp-2022-330851

    PubMed

    researchmap

  • Machine Learning Approach for the Prediction of Age-Specific Probability of SCA3 and DRPLA by Survival Curve Analysis

    Yuya Hatano, Tomohiko Ishihara, Sachiko Hirokawa, Osamu Onodera

    Neurology Genetics   9 ( 3 )   e200075 - e200075   2023.5

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    Background and Objectives

    As the number of repeats in the expansion increases, polyglutamine diseases tend to show at a younger age. From this relationship, attempts have been made to predict age at onset by parametric survival analysis. However, a method for a more accurate prediction has been desirable. In this study, we examined 2 methods for survival analysis using machine learning and 6 conventional methods for parametric survival analysis of spinocerebellar ataxia (SCA)3 and dentatorubral-pallidoluysian atrophy (DRPLA).

    Methods

    We compared the performance of 2 machine learning methods of survival analysis (random survival forest [RSF] and DeepSurv) and 6 methods of parametric survival analysis (Weibull, exponential, Gaussian, logistic, loglogistic, and log Gaussian). Training and evaluation were performed using the leave-one-out cross-validation method, and evaluation criteria included root mean squared error (RMSE), mean absolute error (MAE), and the integrated Brier score. The latter was used as the primary end point, and the survival analysis model yielding the best result was used to predict the asymptomatic probability.

    Results

    Among the models examined, the RSF and DeepSurv machine learning methods had a higher prediction accuracy than the parametric methods of survival analysis. For both SCA3 and DRPLA, RSF had a higher accuracy than DeepSurv for the assessment of RMSE (SCA3: 7.37, DRPLA: 10.78), MAE (SCA3: 5.52, DRPLA: 8.17), and the integrated Brier score (SCA3: 0.05, DRPLA: 0.077). Using RSF, we determined the age-specific probability distribution of age at onset based on CAG repeat size and current age.

    Discussion

    In this study, we have demonstrated the superiority of machine learning methods for predicting age at onset of SCA3 and DRPLA using survival analysis. Such accurate prediction of onset will be useful for genetic counseling of carriers and for devising methods to verify the effects of interventions for unaffected individuals.

    DOI: 10.1212/nxg.0000000000200075

    researchmap

  • Genome-wide association study identifies a new susceptibility locus in PLA2G4C for Multiple System Atrophy. International journal

    Yasuo Nakahara, Jun Mitsui, Hidetoshi Date, Kristine Joyce Porto, Yasuhiro Hayashi, Atsushi Yamashita, Yoshio Kusakabe, Takashi Matsukawa, Hiroyuki Ishiura, Tsutomu Yasuda, Atsushi Iwata, Jun Goto, Yaeko Ichikawa, Yoshio Momose, Yuji Takahashi, Tatsushi Toda, Rikifumi Ohta, Jun Yoshimura, Shinichi Morishita, Emil K Gustavsson, Darren Christy, Melissa Maczis, Matthew J Farrer, Han-Joon Kim, Sung-Sup Park, Beomseok Jeon, Jin Zhang, Weihong Gu, Sonja W Scholz, Andrew B Singleton, Henry Houlden, Ichiro Yabe, Hidenao Sasaki, Masaaki Matsushima, Hiroshi Takashima, Akio Kikuchi, Masashi Aoki, Kenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Ken Yamamoto, Mihoko Shimada, Taku Miyagawa, Yosuke Kawai, Nao Nishida, Katsushi Tokunaga, Alexandra Dürr, Alexis Brice, Alessandro Filla, Thomas Klockgether, Ullrich Wüllner, Caroline M Tanner, Walter A Kukull, Virginia M-Y Lee, Eliezer Masliah, Phillip A Low, Paola Sandroni, Laurie Ozelius, Tatiana Foroud, Shoji Tsuji

    medRxiv : the preprint server for health sciences   2023.5

     More details

    Language:English  

    To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association ( P = 6.5 × 10 -7 ) that was replicated in additional Japanese samples ( P = 2.9 × 10 -6 . OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data ( P = 5.0 × 10 -15 . Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples ( P =0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in PLA2G4C that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.

    DOI: 10.1101/2023.05.02.23289328

    PubMed

    researchmap

  • High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. International journal

    Jun Mitsui, Takashi Matsukawa, Yukari Uemura, Takuya Kawahara, Ayaka Chikada, Kristine Joyce L Porto, Hiroya Naruse, Masaki Tanaka, Hiroyuki Ishiura, Tatsushi Toda, Haruko Kuzuyama, Mari Hirano, Ikue Wada, Toshio Ga, Takashi Moritoyo, Yuji Takahashi, Hidehiro Mizusawa, Kinya Ishikawa, Takanori Yokota, Satoshi Kuwabara, Nobukatsu Sawamoto, Ryosuke Takahashi, Koji Abe, Tomohiko Ishihara, Osamu Onodera, Dai Matsuse, Ryo Yamasaki, Jun-Ichi Kira, Masahisa Katsuno, Ritsuko Hanajima, Katsuhisa Ogata, Hiroshi Takashima, Masaaki Matsushima, Ichiro Yabe, Hidenao Sasaki, Shoji Tsuji

    EClinicalMedicine   59   101920 - 101920   2023.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Functionally impaired variants of COQ2, encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in COQ2 is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients. METHODS: This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Patients with MSA were randomly assigned (1:1) to either ubiquinol (1500 mg/day) or placebo. The primary efficacy outcome was the change in the unified multiple system atrophy rating scale (UMSARS) part 2 at 48 weeks. Efficacy was assessed in all patients who completed at least one efficacy assessment (full analysis set). Safety analyses included patients who completed at least one dose of investigational drug. This trial is registered with UMIN-CTR (UMIN000031771), where the drug name of MSA-01 was used to designate ubiquinol. FINDINGS: Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (-1.7 [95% CI, -3.2 to -0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]). INTERPRETATION: High-dose ubiquinol was well-tolerated and led to a significantly smaller decline of UMSARS part 2 score compared with placebo. FUNDING: Japan Agency for Medical Research and Development.

    DOI: 10.1016/j.eclinm.2023.101920

    PubMed

    researchmap

  • A human induced pluripotent stem cell model from a patient with hereditary cerebral small vessel disease carrying a heterozygous R302Q mutation in HTRA1. International journal

    Emi Qian, Masahiro Uemura, Hiroya Kobayashi, Shiho Nakamura, Fumiko Ozawa, Sho Yoshimatsu, Mitsuru Ishikawa, Osamu Onodera, Satoru Morimoto, Hideyuki Okano

    Inflammation and regeneration   43 ( 1 )   23 - 23   2023.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an inherited cerebral small vessel disease (CSVD) caused by biallelic mutations in the high-temperature requirement serine peptidase A1 (HTRA1) gene. Even heterozygous mutations in HTRA1 are recently revealed to cause cardinal clinical features of CSVD. Here, we report the first establishment of a human induced pluripotent stem cell (hiPSC) line from a patient with heterozygous HTRA1-related CSVD. Peripheral blood mononuclear cells (PBMCs) were reprogrammed by the transfection of episomal vectors encoding human OCT3/4 (POU5F1), SOX2, KLF4, L-MYC, LIN28, and a murine dominant-negative mutant of p53 (mp53DD). The established iPSCs had normal morphology as human pluripotent stem cells and normal karyotype (46XX). Moreover, we found that the HTRA1 missense mutation (c.905G>A, p.R302Q) was heterozygous. These iPSCs expressed pluripotency-related markers and had the potential to differentiate into all three germ layers in vitro. HTRA1 and the supposed disease-associated gene NOG were differentially expressed in the patient iPSCs at mRNA levels compared to those of control lines. The iPSC line would facilitate in vitro research for understanding the cellular pathomechanisms caused by the HTRA1 mutation including its dominant-negative effect.

    DOI: 10.1186/s41232-023-00273-7

    PubMed

    researchmap

  • 遺伝性痙性対麻痺を呈しGTP cyclohydrolase 1ヘテロ接合性変異を認めた1剖検例

    本郷 祥子, 他田 真理, 池田 哲彦, 小澤 哲夫, 劉 李きん, 宮下 哲典, 池内 健, 小野寺 理, 中島 孝, 柿田 明美

    信州医学雑誌   71 ( 2 )   128 - 129   2023.4

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • Novel Partial Deletions, Frameshift and Missense Mutations of CSF1R in Patents with CSF1R-Related Leukoencephalopathy. International journal

    Takanobu Ishiguro, Takuya Konno, Norikazu Hara, Bin Zhu, Satoshi Okada, Mamoru Shibata, Reiko Saika, Takaya Kitano, Megumi Toko, Tomohisa Nezu, Yuka Hama, Tomoya Kawazoe, Ikuko Takahashi-Iwata, Ichiro Yabe, Kota Sato, Hayato Takeda, Shintaro Toda, Jin Nishimiya, Toshiyuki Teduka, Hiroaki Nozaki, Kensaku Kasuga, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi

    European journal of neurology   30 ( 7 )   1861 - 1870   2023.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features. METHODS: Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study. RESULTS: We identified CSF1R mutations in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3-bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. We identified two partial deletions of CSF1R that resulted in the lack of the C-terminal region, including the distal TKD, in two patients. Variable clinical features including cognitive impairment, psychiatric symptoms, and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on MRI and characteristic calcifications on CT were observed as imaging features. CONCLUSIONS: Our results highlighted the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveal no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.

    DOI: 10.1111/ene.15796

    PubMed

    researchmap

  • 脳血管造影検査後の発熱・意識障害で診断された神経核内封入体病(NIID)の一例

    小出 伸, 坪口 晋太朗, 二宮 格, 齋藤 太希, 石黒 敬信, 佐治 越爾, 鈴木 倫明, 金澤 雅人, 小野寺 理

    臨床神経学   63 ( 3 )   180 - 180   2023.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Cataract Surgery and Chronic Kidney Disease: A Hospital-based Prospective Cohort Study

    Minako Wakasugi, Akio Yokoseki, Masakazu Wada, Takaiko Yoshino, Takeshi Momotsu, Kenji Sato, Hiroyuki Kawashima, Kazutoshi Nakamura, Takeo Fukuchi, Osamu Onodera, Ichiei Narita

    Internal Medicine   2023

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.2176-23

    researchmap

  • Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications. International journal

    Yuka Koike, Osamu Onodera

    Frontiers in neuroscience   17   1131758 - 1131758   2023

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Currently, there are no effective biomarkers and fundamental therapies for this disease. Dysregulation in RNA metabolism plays a critical role in the pathogenesis of ALS. With the contribution of Next Generation Sequencing, the functions of non-coding RNAs (ncRNAs) have gained increasing interests. Especially, micro RNAs (miRNAs), which are tissue-specific small ncRNAs of about 18-25 nucleotides, have emerged as key regulators of gene expression to target multiple molecules and pathways in the central nervous system (CNS). Despite intensive recent research in this field, the crucial links between ALS pathogenesis and miRNAs remain unclear. Many studies have revealed that ALS-related RNA binding proteins (RBPs), such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), regulate miRNAs processing in both the nucleus and cytoplasm. Of interest, Cu2+/Zn2+ superoxide dismutase (SOD1), a non-RBP associated with familial ALS, shows partially similar properties to these RBPs via the dysregulation of miRNAs in the cellular pathway related to ALS. The identification and validation of miRNAs are important to understand the physiological gene regulation in the CNS, and the pathological implications in ALS, leading to a new avenue for early diagnosis and gene therapies. Here, we offer a recent overview regarding the mechanism underlying the functions of multiple miRNAs across TDP-43, FUS, and SOD1 with the context of cell biology, and challenging for clinical applications in ALS.

    DOI: 10.3389/fnins.2023.1131758

    PubMed

    researchmap

  • Regeneration of the cerebral cortex by direct chemical reprogramming of macrophages into neuronal cells in acute ischemic stroke. International journal

    Itaru Ninomiya, Akihide Koyama, Yutaka Otsu, Osamu Onodera, Masato Kanazawa

    Frontiers in cellular neuroscience   17   1225504 - 1225504   2023

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Theoretically, direct chemical reprogramming of somatic cells into neurons in the infarct area represents a promising regenerative therapy for ischemic stroke. Previous studies have reported that human fibroblasts and astrocytes transdifferentiate into neuronal cells in the presence of small molecules without introducing ectopic transgenes. However, the optimal combination of small molecules for the transdifferentiation of macrophages into neurons has not yet been determined. The authors hypothesized that a combination of small molecules could induce the transdifferentiation of monocyte-derived macrophages into neurons and that the administration of this combination may be a regenerative therapy for ischemic stroke because monocytes and macrophages are directly involved in the ischemic area. Transcriptomes and morphologies of the cells were compared before and after stimulation using RNA sequencing and immunofluorescence staining. Microscopic analyses were also performed to identify cell markers and evaluate functional recovery by blinded examination following the administration of small molecules after ischemic stroke in CB-17 mice. In this study, an essential combination of six small molecules [CHIR99021, Dorsomorphin, Forskolin, isoxazole-9 (ISX-9), Y27632, and DB2313] that transdifferentiated monocyte-derived macrophages into neurons in vitro was identified. Moreover, administration of six small molecules after cerebral ischemia in model animals generated a new neuronal layer in the infarct cortex by converting macrophages into neuronal cells, ultimately improving neurological function. These results suggest that altering the transdifferentiation of monocyte-derived macrophages by the small molecules to adjust their adaptive response will facilitate the development of regenerative therapies for ischemic stroke.

    DOI: 10.3389/fncel.2023.1225504

    PubMed

    researchmap

  • <i>SYNE1</i>-ataxia: clinicopathologic features of an autopsied patient with novel compound heterozygous mutations

    Rie Saito, Norikazu Hara, Mari Tada, Masatoshi Wakabayashi, Akinori Miyashita, Masatoyo Nishizawa, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Journal of Neuropathology &amp; Experimental Neurology   2022.12

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    DOI: 10.1093/jnen/nlac120

    researchmap

  • Deep learning classification of urinary sediment crystals with optimal parameter tuning. International journal

    Takahiro Nagai, Osamu Onodera, Shujiro Okuda

    Scientific reports   12 ( 1 )   21178 - 21178   2022.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The examination of urinary sediment crystals, the sedimentary components of urine, is useful in screening tests, and is always performed in medical examinations. The examination of urinary sediment crystals is typically done by classifying them under a microscope. Although automated analyzers are commercially available, manual classification is required, which is time-consuming and varies depending on the technologist performing the test and the laboratory. A set of test images was created, consisting of training, validation, and test images. The training images were transformed and augmented using various methods. The test images were classified to determine the patterns that could be correctly classified. Convolutional neural networks were used for training. Furthermore, we also considered the case where the crystal subcategories were not treated as separate. Learning with all parameters except the random cropping parameter showed the highest accuracy value. Treating the subcategories together or separately did not seem to affect the accuracy value. The accuracy of the best pattern was 0.918. When matched to a real-world case, the percentage of correct answers was 88%. Although the number of images was limited, good results were obtained in the classification of crystal images with optimal parameter tuning. The parameter optimization performed in this study can be used as a reference for future studies, with the goal of image classification by deep learning in clinical practice.

    DOI: 10.1038/s41598-022-25385-x

    PubMed

    researchmap

  • High frequency of<i>HTRA1</i>AND<i>ABCC6</i>mutations in Japanese patients with adult-onset cerebral small vessel disease

    Masahiro Uemura, Yuya Hatano, Hiroaki Nozaki, Shoichiro Ando, Hajime Kondo, Akira Hanazono, Akira Iwanaga, Hiroyuki Murota, Yosuke Osakada, Masato Osaki, Masato Kanazawa, Mitsuyasu Kanai, Yoko Shibata, Reiko Saika, Tadashi Miyatake, Hitoshi Aizawa, Takeshi Ikeuchi, Hidekazu Tomimoto, Ikuko Mizuta, Toshiki Mizuno, Tomohiko Ishihara, Osamu Onodera

    Journal of Neurology, Neurosurgery &amp; Psychiatry   jnnp - 2022   2022.10

     More details

    Publishing type:Research paper (scientific journal)   Publisher:BMJ  

    Background

    This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan.

    Methods

    This study included patients with adult-onset severe CSVD with an age of onset ≤55 years (group 1) or &gt;55 years and with a positive family history (group 2). After conducting conventional genetic tests forNOTCH3andHTRA1, whole-exome sequencing was performed on undiagnosed patients. Patients were divided into two groups according to the results of the genetic tests: monogenic and undetermined. The clinical and imaging features were compared between the two groups.

    Results

    Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients hadNOTCH3mutations, 11 patients hadHTRA1mutations, 6 patients hadABCC6mutations, 1 patient had aTREX1mutation, 1 patient had aCOL4A1mutation and 1 patient had aCOL4A2mutation. The total frequency of mutations inNOTCH3,HTRA1andABCC6was 94.0% in patients with mgCSVD. In group 1, the frequency of a family history of first relatives, hypertension and multiple lacunar infarctions (LIs) differed significantly between the two groups (monogenic vs undetermined; family history of first relatives, 61.0% vs 25.0%, p=0.0015; hypertension, 34.1% vs 63.9%, p=0.0092; multiple LIs, 87.8% vs 63.9%, p=0.0134).

    Conclusions

    More than 90% of mgCSVDs were diagnosed by screening forNOTCH3,HTRA1andABCC6. The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.

    DOI: 10.1136/jnnp-2022-329917

    researchmap

  • Patients with heterozygous HTRA1-related cerebral small vessel disease misdiagnosed with other diseases: Two case reports Reviewed

    Sho Kitahara, Shintaro Tsuboguchi, Masahiro Uemura, Hiroaki Nozaki, Masato Kanazawa, Osamu Onodera

    Clinical Neurology and Neurosurgery   2022.10

  • 脳梗塞に対する低酸素低糖刺激末梢血単核球投与による脳内変化

    金山 武史, 畠山 公大, 大津 裕, 秋山 夏葵, 二宮 格, 小野寺 理, 下畑 享良, 金澤 雅人

    脳循環代謝   34 ( 1 )   154 - 154   2022.10

     More details

    Language:Japanese   Publisher:(一社)日本脳循環代謝学会  

    researchmap

  • Biallelic <i>COX10</i> Mutations and <i>PMP22</i> Deletion in a Family With Leigh Syndrome and Hereditary Neuropathy With Liability to Pressure Palsy

    Yasuko Kuroha, Takanobu Ishiguro, Mari Tada, Norikazu Hara, Kei Murayama, Izumi Kawachi, Kensaku Kasuga, Akinori Miyashita, Arika Hasegawa, Tetsuya Takahashi, Nae Matsubara, Osamu Onodera, Akiyoshi Kakita, Ryoko Koike, Takeshi Ikeuchi

    Neurology Genetics   8 ( 5 )   e200030 - e200030   2022.10

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    Objectives

    Leigh syndrome is a progressive encephalopathy characterized by symmetrical lesions in brain. This study aimed to investigate the clinicopathologic and genetic characteristics of a family with Leigh syndrome and hereditary neuropathy with liability to pressure palsy (HNPP).

    Methods

    Data from a Japanese family's clinical features, MRIs, muscle biopsy, and an autopsy were analyzed. A whole-exome sequence was performed, as well as real-time PCR analysis to determine copy number variations and Western blot analyses.

    Results

    The proband and her 2 siblings developed spastic paraplegia and mental retardation during childhood. The proband and her sister had peripheral neuropathy, whereas their father developed compression neuropathy. Leigh encephalopathy was diagnosed neuropathologically. Brain MRI revealed changes in cerebral white matter as well as multiple lesions in the brainstem and cerebellum. Muscle biopsy revealed type 2 fiber uniformity and decreased staining of cytochrome c oxidase. The COX10 missense mutation was identified through whole-exome sequence. A 1.4-Mb genomic deletion extending from intron 5 of COX10 to PMP22 was detected.

    Discussion

    These findings suggest that in this family, Leigh syndrome is associated with a mitochondrial respiratory chain complex IV deficiency caused by biallelic COX10 mutations coexisting with HNPP caused by heterozygous PMP22 deletion.

    DOI: 10.1212/nxg.0000000000200030

    researchmap

  • Dysarthria-facial paresis syndrome due to long insular artery infarction

    Ryutaro Hanyu, Shintaro Tsuboguchi, Itaru Ninomiya, Takanobu Ishiguro, Takuya Konno, Masato Kanazawa, Osamu Onodera

    Journal of the Neurological Sciences   120456 - 120456   2022.10

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jns.2022.120456

    researchmap

  • The CAG repeat length of CACNA1A in both alleles affects the age of onset of SCA6(タイトル和訳中)

    Hatano Yuya, Ishihara Tomohiko, Hirokawa Sachiko, Onodera Osamu

    臨床神経学   62 ( Suppl. )   S364 - S364   2022.10

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • 神経症状で初発する血管内大細胞型B細胞リンパ腫の臨床的特徴と診断方法に関する検討

    北原 匠, 金澤 雅人, 徳武 孝充, 棗田 学, 佐藤 晶, 石川 正典, 原 賢寿, 田部 浩行, 牧野 邦比古, 藤田 信也, 岡本 浩一郎, 柿田 明美, 藤井 幸彦, 小野寺 理

    臨床神経学   62 ( Suppl. )   S272 - S272   2022.10

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Importance of the Q/N-rich segment for protein stability of endogenous mouse TDP-43. International journal

    Toshiya Sato, Kanako Oda, Seiko Sakai, Rika Kato, Saori Yamamori, Makoto Itakura, Yoshio Kodera, Masatoyo Nishizawa, Toshikuni Sasaoka, Osamu Onodera, Minesuke Yokoyama

    Scientific reports   12 ( 1 )   14923 - 14923   2022.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    TAR DNA-binding protein 43 kDa (TDP-43), a nuclear protein, plays an important role in the molecular pathogenesis of amyotrophic lateral sclerosis (ALS). The long-disordered C-terminal region (CTR) of TDP-43 is known to be aggregation-prone and a hotspot for ALS mutations, so elucidation of the physiological function of CTR will provide insights into the pathogenesis of ALS. The CTR has two Gly, aromatic, and Ser-rich (GaroS) segments and an amyloidogenic core divided into a hydrophobic patch (HP) and a Gln/Asn (Q/N)-rich segment. Although TDP-43 lacking the CTR is known to be unstable, as observed in knock-in mice, it is unclear which of these segments contributes to the stability of TDP-43. Here, we generated 12 mouse lines lacking the various sub-regions of CTR by genome editing and compared the embryonic lethality of homozygotes, and protein and mRNA expression levels of TDP-43. We demonstrated the functional diversity of the four segments of CTR, finding that the presence of the Q/N-rich segment greatly restored the protein stability of TDP-43. In addition, we found that the second GaroS deletion did not affect protein stability and mouse development.

    DOI: 10.1038/s41598-022-19153-0

    PubMed

    researchmap

  • 失語症を来した小脳出血の1例

    畠山 公大, 大槻 美佳, 木下 悠紀子, 小出 伸, 畠山 祐樹, 佐治 越爾, 金澤 雅人, 小野寺 理

    日本神経心理学会総会プログラム・予稿集   46回   69 - 69   2022.8

     More details

    Language:Japanese   Publisher:日本神経心理学会  

    researchmap

  • Clinical correlations of cerebrospinal fluid biomarkers including neuron-glia 2 and neurofilament light chain in patients with multiple system atrophy. International journal

    Takayoshi Tokutake, Kensaku Kasuga, Tamao Tsukie, Takanobu Ishiguro, Takayoshi Shimohata, Osamu Onodera, Takeshi Ikeuchi

    Parkinsonism & related disorders   102   30 - 35   2022.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder. The usefulness of biomarkers in diagnosing MSA has been recently reported, but few studies have investigated the correlations among cerebrospinal fluid (CSF) biomarkers or the relationship between CSF biomarkers and the clinical parameters of patients with MSA. Thus, this was the aim of our study. METHODS: We performed cross-sectional study of CSF biomarkers in 50 patients with MSA and 20 control subjects. Ten of the patients with MSA were longitudinally followed for a period of 2 ± 1 years (mean ± standard deviation) as a substudy. We quantified CSF biomarkers including α-synuclein (α-syn), β-amyloid42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau), neurofilament light chain (NfL), and neuron-glia2 (NG2), and assessed their relationship with clinical parameters (clinical subtypes, motor symptoms, nonmotor symptoms, and disease progression). RESULTS: The levels of CSF α-syn, Aβ42, and p-tau were significantly lower, while those of NfL were higher in the patients with MSA than in the control subjects. Importantly, we found the significant elevation of soluble NG2 in the CSF of patients with MSA. CSF NfL showed the optimal diagnostic performance for MSA with levels at baseline significantly associated with longitudinal motor progression. With the exception of t-tau, there were no differences in the levels of CSF biomarkers between the MSA-parkinsonism and MSA-cerebellar subtypes. CONCLUSIONS: Our results suggest CSF levels of NG2 and NfL as possible diagnostic and prognostic biomarkers in MSA. Further study is necessary to validate these findings.

    DOI: 10.1016/j.parkreldis.2022.07.007

    PubMed

    researchmap

  • Stroke incidence and chronic kidney disease: A hospital-based prospective cohort study. International journal

    Minako Wakasugi, Akio Yokoseki, Masakazu Wada, Kazuhiro Sanpei, Takeshi Momotsu, Kenji Sato, Hiroyuki Kawashima, Kazutoshi Nakamura, Osamu Onodera, Ichiei Narita

    Nephrology (Carlton, Vic.)   27 ( 7 )   577 - 587   2022.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    AIM: This prospective cohort study aimed to (i) examine stroke incidence and stroke subtypes by chronic kidney disease (CKD) stage, (ii) examine whether CKD patients with or without proteinuria have a high risk of stroke independent of traditional cardiovascular risk factors, and (iii) determine precise estimates of stroke risk by CKD stage while accounting for competing mortality risk. METHODS: Participants were 2023 patients enrolled in the Project in Sado for Total Health between June 2008 and December 2016 (55% men; mean age, 69 years), of whom 52% had CKD (stage 1-2, 10%; G3a, 48%; G3b, 17%; G4-5, 11% and G5D, 14%). RESULTS: During a median follow-up of 5.7 years, 157 participants developed stroke and 448 died without developing stroke. Most stroke cases were ischaemic among non-dialysis-dependent CKD participants, but the relative frequency of ischaemic stroke was near that of intracerebral haemorrhage among dialysis-dependent CKD participants. After adjustment, stage 1-2 (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.60-5.51) and stage G3-5 participants with proteinuria (HR, 2.50; 95% CI, 1.56-4.02), but not stage G3-5 participants without proteinuria (HR, 0.64; 95% CI, 0.38-1.08), had a higher stroke risk compared to non-CKD participants. In competing risk analyses, the association was attenuated but remained significant. CONCLUSION: Although the distribution of stroke subtypes differed, CKD participants with proteinuria and those with CKD stage 5D had a 2- and 4-times higher risk of stroke, respectively, than that of non-CKD participants, after accounting for competing mortality risk and traditional risk factors.

    DOI: 10.1111/nep.14049

    Web of Science

    PubMed

    researchmap

  • Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. International journal

    Ryosuke Oki, Yuishin Izumi, Koji Fujita, Ryosuke Miyamoto, Hiroyuki Nodera, Yasutaka Sato, Satoshi Sakaguchi, Hiroshi Nokihara, Kazuaki Kanai, Taiji Tsunemi, Nobutaka Hattori, Yuki Hatanaka, Masahiro Sonoo, Naoki Atsuta, Gen Sobue, Toshio Shimizu, Kazumoto Shibuya, Ken Ikeda, Osamu Kano, Kazuto Nishinaka, Yasuhiro Kojima, Masaya Oda, Kiyonobu Komai, Hitoshi Kikuchi, Nobuo Kohara, Makoto Urushitani, Yoshiaki Nakayama, Hidefumi Ito, Makiko Nagai, Kazutoshi Nishiyama, Daisuke Kuzume, Shun Shimohama, Takayoshi Shimohata, Koji Abe, Tomohiko Ishihara, Osamu Onodera, Sagiri Isose, Nobuyuki Araki, Mitsuya Morita, Kazuyuki Noda, Tatsushi Toda, Hirofumi Maruyama, Hirokazu Furuya, Satoshi Teramukai, Tatsuo Kagimura, Kensuke Noma, Hiroaki Yanagawa, Satoshi Kuwabara, Ryuji Kaji

    JAMA neurology   79 ( 6 )   575 - 583   2022.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Importance: The effectiveness of currently approved drugs for amyotrophic lateral sclerosis (ALS) is restricted; there is a need to develop further treatments. Initial studies have shown ultrahigh-dose methylcobalamin to be a promising agent. Objective: To validate the efficacy and safety of ultrahigh-dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design, Setting, and Participants: This was a multicenter, placebo-controlled, double-blind, randomized phase 3 clinical trial with a 12-week observation and 16-week randomized period, conducted from October 17, 2017, to September 30, 2019. Patients were recruited from 25 neurology centers in Japan; those with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score, a percent forced vital capacity greater than 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulatory. The target participant number was 64 in both the methylcobalamin and placebo groups. Patients were randomly assigned through an electronic web-response system to methylcobalamin or placebo. Interventions: Intramuscular injection of methylcobalamin (50-mg dose) or placebo twice weekly for 16 weeks. Main Outcomes and Measures: The primary end point was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: A total of 130 patients (mean [SD] age, 61.0 [11.7] years; 74 men [56.9%]) were randomly assigned to methylcobalamin or placebo (65 each). A total of 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Of these, 124 patients proceeded to the open-label extended period. The least square means difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (-2.66 vs -4.63; 95% CI, 0.44-3.50; P = .01). The incidence of adverse events was similar between the 2 groups. Conclusions and Relevance: Results of this randomized clinical trial showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in patients with early-stage ALS and with moderate progression rate and was safe to use during the 16-week treatment period. Trial Registration: ClinicalTrials.gov Identifier: NCT03548311.

    DOI: 10.1001/jamaneurol.2022.0901

    PubMed

    researchmap

  • 全身性疾患に伴う脊椎病変 頸椎除圧術後の上肢型筋萎縮側索硬化症の臨床経過

    五十嵐 哲也, 渡辺 慶, 大橋 正幸, 川島 寛之, 三瓶 一弘, 五十嵐 修一, 黒羽 泰子, 小池 亮子, 石原 智彦, 大津 裕, 小野寺 理

    東北整形災害外科学会雑誌   65 ( 1 )   167 - 168   2022.6

     More details

    Language:Japanese   Publisher:東北整形災害外科学会  

    researchmap

  • Paving the Way Toward Meaningful Trials in Ataxias: An Ataxia Global Initiative Perspective. International journal

    Thomas Klockgether, Tetsuo Ashizawa, Bernard Brais, Rosalind Chuang, Alexandra Durr, Brent Fogel, Julie Greenfield, Sue Hagen, Laura Bannach Jardim, Hong Jiang, Osamu Onodera, José Luiz Pedroso, Bin-Weng Soong, David Szmulewicz, Holm Graessner, Matthis Synofzik

    Movement disorders : official journal of the Movement Disorder Society   37 ( 6 )   1125 - 1130   2022.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/mds.29032

    PubMed

    researchmap

  • 臨床医のための神経病理再入門 CARASIL

    齋藤 理恵, 小野寺 理, 柿田 明美

    Clinical Neuroscience   40 ( 6 )   700 - 702   2022.6

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 脳神経疾患克服に向けた研究推進の提言2020、各論(疾患群別)

    望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 高橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会

    臨床神経学   62 ( 6 )   443 - 457   2022.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    日本神経学会では,脳神経内科領域の研究・教育・診療,特に研究の方向性や学会としてのあるべき姿について審議し,水澤代表理事が中心となり国などに対して提言を行うために作成委員*が選ばれ,2013年に「脳神経疾患克服に向けた研究推進の提言」が作成された.2014年に将来構想委員会が設立され,これらの事業が継続.今回将来構想委員会で,2020年から2021年の最新の提言が作成された.この各論IIでは,疾患ごとに脳神経内科領域を分類し,各分野の専門家がわかりやすく解説するとともに,最近のトピックスについて冒頭に取り上げた.(著者抄録)

    researchmap

    Other Link: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01550&link_issn=&doc_id=20220609450002&doc_link_id=10.5692%2Fclinicalneurol.cn-001696&url=https%3A%2F%2Fdoi.org%2F10.5692%2Fclinicalneurol.cn-001696&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 脳神経疾患克服に向けた研究推進の提言2020、各論(方法論別)

    望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 高橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会

    臨床神経学   62 ( 6 )   429 - 442   2022.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    日本神経学会では,脳神経内科領域の研究・教育・診療,特に研究の方向性や学会としてのあるべき姿について審議し,水澤代表理事が中心となり国などに対して提言を行うために作成委員*が選ばれ,2013年に「脳神経疾患克服に向けた研究推進の提言」が作成された.2014年に将来構想委員会が設立され,これらの事業が継続.今回将来構想委員会で,2020年から2021年の最新の提言が作成された.この各論Iでは,遺伝子研究,トランスレーショナルリサーチ,核酸医薬,iPS研究,介護・福祉など,多様性を増す脳神経内科領域の臨床と研究について,最新トピックスを交えて取り上げる.(著者抄録)

    researchmap

    Other Link: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01550&link_issn=&doc_id=20220609450001&doc_link_id=10.5692%2Fclinicalneurol.cn-001695&url=https%3A%2F%2Fdoi.org%2F10.5692%2Fclinicalneurol.cn-001695&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Mortality factors in recurrent parathyroid cancer: a pooled analysis reply

    Minako Wakasugi, Akio Yokoseki, Masakazu Wada, Takeshi Momotsu, Kenji Sato, Hiroyuki Kawashima, Kazutoshi Nakamura, Osamu Onodera, Ichiei Narita

    JOURNAL OF BONE AND MINERAL METABOLISM   40 ( 3 )   537 - 538   2022.5

     More details

    Language:English   Publisher:SPRINGER JAPAN KK  

    DOI: 10.1007/s00774-022-01315-9

    Web of Science

    researchmap

  • Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020

    M.D., Ph.D. Mochizuki Hideki, M.D., Ph.D. Aoki Masashi, M.D., Ph.D. Ikenaka Kensuke, M.D., Ph.D. Inoue Haruhisa, M.D., Ph.D. Iwatsubo Takeshi, M.D., Ph.D. Ugawa Yoshikazu, M.D., Ph.D. Okazawa Hitoshi, M.D., Ph.D. Ono Kenjiro, M.D., Ph.D. Onodera Osamu, M.D., Ph.D. Kitagawa Kazuo, M.D., Ph.D. Saito Yuko, M.D., Ph.D. Shimohata Takayoshi, M.D., Ph.D. Takahashi Ryosuke, M.D., Ph.D. Toda Tatsushi, M.D., Ph.D. Nakahara Jin, M.D., Ph.D. Matsumoto Riki, M.D., Ph.D. Mizusawa Hidehiro, M.D., Ph.D. Mitsui Jun, M.D., Ph.D. Murayama Shigeo, M.D., Ph.D. Katsuno Masahisa, the Future Vision Committee of Japanese Society of Neurology, M.D., Ph.D. Aoki Yoshitsugu, M.D., Ph.D. Ishiura Hiroyuki, M.D., Ph.D. Izumi Yuishin, M.D., Ph.D. Koike Haruki, M.D., Ph.D. Shimada Hitoshi, M.D., Ph.D. Takahashi Yuji, M.D., Ph.D. Tokuda Takahiko, M.D., Ph.D. Nakajima Hideto, M.D., Ph.D. Hatano Taku, M.D., Ph.D. Misawa Sonoko, M.D., Ph.D. Watanabe Hirohisa

    Rinsho Shinkeigaku   advpub ( 6 )   443 - 457   2022.5

     More details

    Language:Japanese   Publisher:Societas Neurologica Japonica  

    The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this section II, we will discuss clinical and research topics of neurology categorized by the diseases. In each field, the hot topic of the disease was described by the expert.

    DOI: 10.5692/clinicalneurol.cn-001696

    PubMed

    researchmap

  • Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020

    M.D., Ph.D. Mochizuki Hideki, M.D., Ph.D. Aoki Masashi, M.D., Ph.D. Ikenaka Kensuke, M.D., Ph.D. Inoue Haruhisa, M.D., Ph.D. Iwatsubo Takeshi, M.D., Ph.D. Ugawa Yoshikazu, M.D., Ph.D. Okazawa Hitoshi, M.D., Ph.D. Ono Kenjiro, M.D., Ph.D. Onodera Osamu, M.D., Ph.D. Kitagawa Kazuo, M.D., Ph.D. Saito Yuko, M.D., Ph.D. Shimohata Takayoshi, M.D., Ph.D. Takahashi Ryosuke, M.D., Ph.D. Toda Tatsushi, M.D., Ph.D. Nakahara Jin, M.D., Ph.D. Matsumoto Riki, M.D., Ph.D. Mizusawa Hidehiro, M.D., Ph.D. Mitsui Jun, M.D., Ph.D. Murayama Shigeo, M.D., Ph.D. Katsuno Masahisa, the Future Vision Committee of Japanese Society of Neurology, M.D., Ph.D. Aoki Yoshitsugu, M.D., Ph.D. Ishiura Hiroyuki, M.D., Ph.D. Izumi Yuishin, M.D., Ph.D. Koike Haruki, M.D., Ph.D. Shimada Hitoshi, M.D., Ph.D. Takahashi Yuji, M.D., Ph.D. Tokuda Takahiko, M.D., Ph.D. Nakajima Hideto, M.D., Ph.D. Hatano Taku, M.D., Ph.D. Misawa Sonoko, M.D., Ph.D. Watanabe Hirohisa

    Rinsho Shinkeigaku   advpub ( 6 )   429 - 442   2022.5

     More details

    Language:Japanese   Publisher:Societas Neurologica Japonica  

    The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this section I, we will discuss clinical and research topics of neurology categorized by the methodology, including genetic research, translational research, nucleic acid therapies, iPS research, and nursing/welfare.

    DOI: 10.5692/clinicalneurol.cn-001695

    PubMed

    researchmap

  • [ATTRv amyloidosis with early improvement demonstrated by the 6-minute walk test following Patisiran therapy: a case report].

    Shinya Oginezawa, Tomohiko Ishihara, Yohei Iwafuchi, Yuya Hatano, Ken Kashimura, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   62 ( 5 )   375 - 379   2022.4

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report the case of a 65-year-old man who gradually developed numbness in both hands, lower limb muscle weakness and atrophy, and orthostatic hypotension over two and a half years. These symptoms indicated hereditary ATTR amyloidosis (ATTRv amyloidosis), and the final diagnosis was established through proof of TTR gene mutation (V30M). We initiated patisiran therapy, and a continuous 6-minute walking test performed 3 weeks from the start of therapy demonstrated improvement in the walking distance. This is a single case report showing the improvement in the motor and sensory function on administration of patisiran monotherapy from an early stage.

    DOI: 10.5692/clinicalneurol.cn-001693

    PubMed

    researchmap

  • 禿頭と腰椎症を呈し、ヘテロ接合性HTRA1変異を伴った脳小血管病の31歳女性例

    安田 真人, 杉山 淳比古, 森 雅裕, 水地 智基, 福武 敏夫, 上村 昌寛, 小野寺 理, 桑原 聡

    臨床神経学   62 ( 4 )   314 - 314   2022.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Brain TDP-43 pathology in corticobasal degeneration: Topographical correlation with neuronal loss. International journal

    Makoto Sainouchi, Mari Tada, Yusran Ady Fitrah, Norikazu Hara, Kou Tanaka, Jiro Idezuka, Izumi Aida, Takashi Nakajima, Akinori Miyashita, Kohei Akazawa, Takeshi Ikeuchi, Osamu Onodera, Akiyoshi Kakita

    Neuropathology and applied neurobiology   48 ( 3 )   e12786   2022.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    AIMS: Neuronal and glial inclusions comprising transactive response DNA-binding protein of 43 kDa (TDP-43) have been identified in the brains of patients with corticobasal degeneration (CBD), and a possible correlation between the presence of these inclusions and clinical phenotypes has been speculated. However, the significance of TDP-43 pathology in the pathomechanism of CBD has remained unclear. Here, we investigated the topographical relationship between TDP-43 inclusions and neuronal loss in CBD. METHODS: We estimated semi-quantitatively neuronal loss and TDP-43 pathology in the form of neuronal cytoplasmic inclusions (NCIs), astrocytic inclusions (AIs), oligodendroglial cytoplasmic inclusions (GCIs), and dystrophic neurites in 22 CNS regions in 10 patients with CBD. Then, the degree of correlation between the severity of neuronal loss and the quantity of each type of TDP-43 inclusion was assessed. We also investigated tau pathology in a similar manner. RESULTS: TDP-43 pathology was evident in nine patients. The putamen and globus pallidus were the regions most frequently affected (80%). NCIs were the most prominent form, and their quantity was significantly correlated with the severity of neuronal loss in more than half of the regions examined. The quantities of TDP-43 NCIs and tau NCIs were correlated in only a few regions. The number of regions where the quantities of TDP-43 AIs and GCIs were correlated with the severity of neuronal loss was apparently small in comparison with that of NCIs. CONCLUSIONS: TDP-43 alterations in neurons, not closely associated with tau pathology, may be involved in the pathomechanism underlying neuronal loss in CBD. There was a significant topographical correlation between neuronal cytoplasmic aggregation of TDP-43 and neuronal loss in CBD, suggesting that TDP-43 protein aberration might be associated with neuronal degeneration in CBD. There was no close correlation between the burden of TDP-43 and that of tau in neurons.

    DOI: 10.1111/nan.12786

    PubMed

    researchmap

  • Authors' reply.

    Minako Wakasugi, Akio Yokoseki, Masakazu Wada, Takeshi Momotsu, Kenji Sato, Hiroyuki Kawashima, Kazutoshi Nakamura, Osamu Onodera, Ichiei Narita

    Journal of bone and mineral metabolism   40 ( 3 )   537 - 538   2022.2

     More details

  • Endogenous human retrovirus-K is not increased in the affected tissues of Japanese ALS patients. International journal

    Tomohiko Ishihara, Akihide Koyama, Yuya Hatano, Ryoko Takeuchi, Yuka Koike, Taisuke Kato, Mari Tada, Akiyoshi Kakita, Osamu Onodera

    Neuroscience research   178   78 - 82   2022.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Activation of human endogenous retrovirus-K (HERV-K) is one of the proposed risk factors for amyotrophic lateral sclerosis (ALS). The HERV-K envelope protein has been reported to show neurotoxicity, and development of therapy with reverse transcriptase inhibitors is being investigated. On the other hand, some reports have failed to show HERV-K activation in ALS. In this study, we analyzed the expression of HERV-K mRNA in the motor cortex and spinal cord of 15 Japanese patients with sporadic ALS and 19 controls using reverse transcriptase droplet digital PCR. This revealed no significant increase of HERV-K expression in ALS-affected tissues, suggesting that the association between ALS and HERV-K remains questionable.

    DOI: 10.1016/j.neures.2022.01.009

    PubMed

    researchmap

  • Stem cell transplantation for pediatric patients with adrenoleukodystrophy: A nationwide retrospective analysis in Japan. International journal

    Koji Kato, Hiromasa Yabe, Nobuyuki Shimozawa, Souichi Adachi, Mineo Kurokawa, Yoshiko Hashii, Atsushi Sato, Nao Yoshida, Makiko Kaga, Osamu Onodera, Shunichi Kato, Yoshiko Atsuta, Tomohiro Morio

    Pediatric transplantation   26 ( 1 )   e14125   2022.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Adrenoleukodystrophy (ALD) is an X-linked recessive disorder and 30-40% of patients develop progressive cerebral neurodegeneration. For symptomatic ALD patients, allogeneic stem cell transplantation (SCT) is considered the standard treatment modality to stabilize or prevent the progression of neurological symptoms. METHODS: We retrospectively analyzed the transplant outcomes of 99 pediatric patients with cerebral ALD in Japan. The conditioning regimens included Regimen A: fludarabine/melphalan/low-dose total body irradiation (TBI) with brain sparing (n = 39), Regimen B; busulfan/cyclophosphamide ± others (n = 23), Regimen C: melphalan/total lymphoid irradiation/thoracoabdominal irradiation ± anti-T lymphocyte globulin ± fludarabine (n = 27), and Regimen D: others (n = 10). RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) of all patients were 90.0% and 72.9%, respectively. The 5-year OS was 100.0% for Regimen A, 91.1% for Regimen B, 84.4% for Regimen C, and 67.5% for Regimen D (p = 0.028). The 5-year EFS was 78.3% for Regimen A, 78.0% for Regimen B, 70.4% for Regimen C, and 48.0% for Regimen D (p = 0.304). The OS marginally improved after 2007 compared with before 2006 (95.3% vs. 85.2%, p = 0.066), due to the improvement of cord blood transplantation (CBT) outcomes after 2007 compared with before 2006 (96.6% vs. 68.4%, p = 0.005). On magnetic resonance imaging of the brain, a reduced Loes score after SCT was only observed in one of the 15 bone marrow transplantation (BMT) patients, but in 5 of the 15 CBT patients (p = 0.173). CONCLUSIONS: Our study revealed that a reduced conditioning regimen with fludarabine/melphalan/low-dose TBI provides better outcomes, and the results of CBT significantly improved after 2007.

    DOI: 10.1111/petr.14125

    PubMed

    researchmap

  • USP10 inhibits aberrant cytoplasmic aggregation of TDP-43 by promoting stress granule clearance. International journal

    Masahiko Takahashi, Hiroki Kitaura, Akiyoshi Kakita, Taichi Kakihana, Yoshinori Katsuragi, Osamu Onodera, Yuriko Iwakura, Hiroyuki Nawa, Masaaki Komatsu, Masahiro Fujii

    Molecular and cellular biology   42 ( 3 )   MCB0039321   2022.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    TDP-43 is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates: stress granules (SGs) first, and then aggresomes. Accumulating evidence suggests that delayed clearance of TDP-43-positive SGs is associated with pathological TDP-43 aggregates in ALS. We found that USP10 promotes the clearance of TDP-43-positive SGs in cells treated with proteasome inhibitor, thereby promoting the formation of TDP-43-positive aggresomes, and the depletion of USP10 increases the amount of insoluble TDP-35, a cleaved product of TDP-43, in the cytoplasm. TDP-35 interacted with USP10 in an RNA-binding dependent manner; however, impaired RNA-binding of TDP-35 reduced the localization in SGs and aggresomes and induced USP10-negative TDP-35 aggregates. Immunohistochemistry showed that most of the cytoplasmic TDP-43/TDP-35-aggregates in the neurons of ALS patients were USP10-negative. Our findings suggest that USP10 inhibits aberrant aggregation of TDP-43/TDP-35 in the cytoplasm of neuronal cells by promoting the clearance of TDP-43/TDP-35-positive SGs and facilitating the formation of TDP-43/TDP-35-positive aggresomes.

    DOI: 10.1128/MCB.00393-21

    PubMed

    researchmap

  • Polypharmacy, chronic kidney disease, and incident fragility fracture: a prospective cohort study.

    Minako Wakasugi, Akio Yokoseki, Masakazu Wada, Takeshi Momotsu, Kenji Sato, Hiroyuki Kawashima, Kazutoshi Nakamura, Osamu Onodera, Ichiei Narita

    Journal of bone and mineral metabolism   40 ( 1 )   157 - 166   2022.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER JAPAN KK  

    INTRODUCTION: Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status. MATERIALS AND METHODS: Participants were 2023 patients (55% men; mean age, 69 years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders. RESULTS: Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6 years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96-1.79) and 1.99 (1.35-2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction P = 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients. CONCLUSION: Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.

    DOI: 10.1007/s00774-021-01272-9

    Web of Science

    PubMed

    researchmap

  • Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy. International journal

    Akira Taniguchi, Akihiro Shindo, Ken-Ichi Tabei, Osamu Onodera, Yukio Ando, Takao Urabe, Kazumi Kimura, Kazuo Kitagawa, Yoshihiro Miyamoto, Misa Takegami, Masafumi Ihara, Ikuko Mizuta, Toshiki Mizuno, Hidekazu Tomimoto

    Frontiers in aging neuroscience   14   876437 - 876437   2022

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Objectives: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL. Methods: Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated. Results: Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia (p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723-0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719-0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551-0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity. Conclusion: The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML.

    DOI: 10.3389/fnagi.2022.876437

    PubMed

    researchmap

  • Neuronal Intranuclear Inclusion Disease Presenting with Voice Tremor International journal

    Tomone Taneda, Masato Kanazawa, Yo Higuchi, Hironori Baba, Aiko Isami, Masahiro Uemura, Takuya Konno, Arata Horii, Takeshi Ikeuchi, Osamu Onodera

    Movement Disorders Clinical Practice   9 ( 3 )   404 - 406   2021.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/mdc3.13382

    PubMed

    researchmap

  • Parkinson's disease and parkinsonism: Clinicopathological discrepancies on diagnosis in three patients. International journal

    Yasuko Toyoshima, Hitoshi Takahashi, Shinnichi Katada, Naoyuki Kojima, Mari Tada, Takashi Tani, Ryoko Koike, Takanori Nozawa, Izumi Aida, Takashi Nakajima, Osamu Onodera, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   41 ( 6 )   450 - 456   2021.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The cardinal neuropathological features of PD include selective and progressive loss of pigmented neurons in the substantia nigra, deficiencies in dopaminergic signaling in the striatum, and occurrence of phosphorylated α-synuclein-identified Lewy bodies in the nervous system. Parkinsonism, the clinical presentation of movement disorders seen in PD, is a feature shared commonly by other pathologically distinct neurodegenerative diseases, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Consequently, it is sometimes difficult to distinguish PD from such parkinsonism-related neurological disorders. In addition, parkinsonism is not always a feature of certain neurodegenerative diseases, and it can sometimes develop as a result of various forms of drug intoxication or cerebrovascular disease. Here, we describe the clinicopathological features of three patients (cases 1, 2, and 3) diagnosed as having PSP, MSA, and PD, respectively, in each of whom the postmortem histopathological diagnosis differed from the final clinical diagnosis. Neuropathologically, they had suffered from coexistent disorders: PD, MSA, and argyrophilic grain disease (case 1); PD (case 2); and vascular parkinsonism (case 3). The variety of patients showing features of parkinsonism underlines the importance of careful long-term follow up followed by postmortem neuropathological evaluation.

    DOI: 10.1111/neup.12777

    PubMed

    researchmap

  • [Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020].

    Hideki Mochizuki, Masashi Aoki, Kensuke Ikenaka, Haruhisa Inoue, Takeshi Iwatsubo, Yoshikazu Ugawa, Hitoshi Okazawa, Kenjiro Ono, Osamu Onodera, Kazuo Kitagawa, Yuko Saito, Takayoshi Shimohata, Ryosuke Takahashi, Tatsushi Toda, Jin Nakahara, Riki Matsumoto, Hidehiro Mizusawa, Jun Mitsui, Shigeo Murayama, Masahisa Katsuno, Yoshitsugu Aoki, Hiroyuki Ishiura, Yuishin Izumi, Haruki Koike, Hitoshi Shimada, Yuji Takahashi, Takahiko Tokuda, Hideto Nakajima, Taku Hatano, Sonoko Misawa, Hirohisa Watanabe

    Rinsho shinkeigaku = Clinical neurology   61 ( 11 )   709 - 721   2021.11

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    The Japanese Society of Neurology discusses research, education, and medical care in the field of neurology and makes recommendations to the national government. Dr. Mizusawa, the former representative director of the Japanese Society of Neurology, selected committee members and made "Recommendations for Promotion of Research for Overcoming Neurological Diseases" in 2013. After that, the Future Vision Committee was established in 2014, and these recommendations have been revised once every few years by the committee. This time, the Future Vision Committee made the latest recommendations from 2020 to 2021. In this document, the general part is 1) What is neurological disease? 2) Current status of neurological disease overcoming research, 3) Significance and necessity of neurological disease overcoming research, 4) Research promotion system for overcoming neurological disease, 5) the roadmap for overcoming neuromuscular diseases, 6) a summary version of these recommendations are explained using figures that are easy for the general public to understand.

    DOI: 10.5692/clinicalneurol.cn-001639

    PubMed

    researchmap

  • ラット脳虚血後のリン酸化タウ発現の経時変化

    大津 裕, 金山 武史, 二宮 格, 畠山 公大, 小野寺 理, 金澤 雅人

    脳循環代謝   33 ( 1 )   96 - 96   2021.11

     More details

    Language:Japanese   Publisher:(一社)日本脳循環代謝学会  

    researchmap

  • 加齢と関連したDNA脱メチル化がTDP-43量の自己調節機構を障害する

    小池 佑佳, 須貝 章弘, 原 範和, 伊藤 絢子, 横関 明男, 石原 智彦, 山岸 拓磨, 坪口 晋太朗, 他田 真理, 池内 健, 柿田 明美, 小野寺 理

    Dementia Japan   35 ( 4 )   610 - 610   2021.10

     More details

    Language:English   Publisher:(一社)日本認知症学会  

    researchmap

  • パチシラン単独投与で早期より運動機能が改善したATTRアミロイドーシスの1例

    荻根沢 真也, 石原 智彦, 岩淵 洋平, 畠野 雄也, 柏村 健, 小野寺 理

    神経治療学   38 ( 6 )   S293 - S293   2021.10

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 神経核内封入体病(NIID)におけるNOTCH2NLCリピート伸長と臨床的特徴の検討

    樋口 陽, 原 範和, Yusran Ady Fitrah, 種田 朝音, 徳武 孝允, 三浦 健, 岩淵 洋平, 五十嵐 修一, 林 秀樹, 石黒 敬信, 三瓶 一弘, 武田 勇人, 高橋 俊昭, 金澤 雅人, 宮下 哲典, 小野寺 理, 池内 健

    Dementia Japan   35 ( 4 )   612 - 612   2021.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Do patients with multiple system atrophy have decreased nocturnal urinary concentration? International journal

    Yusuke Sakata, Masato Kanazawa, Masahiro Hatakeyama, Takuya Konno, Tetsutaro Ozawa, Osamu Onodera

    Clinical autonomic research : official journal of the Clinical Autonomic Research Society   2021.9

     More details

  • 小字症を呈した自己免疫性脳幹脳炎の臨床的特徴

    助川 真響, 畠山 公大, 羽入 龍太郎, 滑川 将気, 大津 裕, 橋田 裕美, 金澤 雅人, 小野寺 理

    臨床神経学   61 ( Suppl. )   S431 - S431   2021.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Hemiplegic-type ALS: clinicopathological features of two autopsied patients. International journal

    Makoto Sainouchi, Hidetomo Tanaka, Hiroshi Shimizu, Takuya Mashima, Takao Fukushima, Yuya Hatano, Tomohiko Ishihara, Kunihiko Makino, Osamu Onodera, Akiyoshi Kakita

    Journal of neurology, neurosurgery, and psychiatry   92 ( 9 )   1014 - 1016   2021.9

     More details

  • [Rethinking Lacunar Stroke: Beyond Fisher's Curse].

    Osamu Onodera, Masahiro Uemura, Shoichiro Ando, Hideki Hayashi, Masato Kanazawa

    Brain and nerve = Shinkei kenkyu no shinpo   73 ( 9 )   991 - 998   2021.9

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Lipohyalinosis is an important concept in the independence of lacunar stroke; however, its role has been overemphasized and has led to much confusion in the understanding of lacunar stroke. Classical lipohyalinosis has declined following the widespread availability of antihypertensive therapy, and lacunar stroke secondary to age-related hyaline atherosclerosis is more commonly observed in clinical practice. Clinically diagnosed lacunar stroke is associated with several etiopathogenetic contributors. Excluding cardiogenic embolism, lacunar stroke can be categorized based on the detection of an atheroma. Atheroma imaging is possible in recent years, and strokes that are not associated with an atheroma are shown to present with deep white matter hyperintensity on MRI. Additionally, risk gene analysis has confirmed a group of risk genes associated with the extracellular matrix in lacunar stroke with white matter hyperintensity on MRI. These findings suggest the role of a variety of etiopathogenetic mechanisms underlying lacunar stroke and that lacunar stroke with deep white matter hyperintensity on MRI may be attributable to unique pathogenetic contributors. This group is known to be strongly associated with genetic contributors. Hopefully, lacunar stroke will be diagnosed from this perspective with the development of interventional strategies tailored to the pathogenesis of this condition.

    DOI: 10.11477/mf.1416201876

    PubMed

    researchmap

  • Visual outcome of aquaporin-4 antibody-positive optic neuritis with maintenance therapy.

    Satoshi Ueki, Tetsuhisa Hatase, Megumi Kiyokawa, Izumi Kawachi, Etsuji Saji, Osamu Onodera, Takeo Fukuchi, Hironaka Igarashi

    Japanese journal of ophthalmology   65 ( 5 )   699 - 703   2021.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    PURPOSE: To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis. STUDY DESIGN: Retrospective study. METHODS: The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative. RESULTS: The mean ages were 49.3 and 45.2 years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01). CONCLUSION: This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis.

    DOI: 10.1007/s10384-021-00858-0

    PubMed

    researchmap

  • [A case of subcortical hemorrhage due to infective endocarditis caused by Staphylococcus warneri without fever and leukocytosis].

    Tomone Taneda, Takuya Konno, Ayaka Ono, Takayoshi Tokutake, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   61 ( 8 )   563 - 566   2021.8

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A 50-year-old man with mitral regurgitation presented with right frontal subcortical hemorrhage. Although he had no fever and his white blood cell count was in the normal range, CT angiography demonstrated a micro cerebral aneurysm, and all three blood cultures were positive for Staphylococcus warneri (S. warneri). Thus, we diagnosed him with infective endocarditis. His condition improved successfully by immediate antibiotics and cerebral aneurysm clipping. S. warneri is a member of coagulase-negative staphylococci that are low-virulence and resident flora of the skin. S. warneri rarely causes infective endocarditis on native valves. Infective endocarditis caused by S. warneri manifests insidious course without inflammatory reactions such as fever and leukocytosis, and thus, diagnosis can be delayed. Attention should be paid to a patient who develops subcortical hemorrhage without a history of hypertension or inflammatory reactions as in this case.

    DOI: 10.5692/clinicalneurol.cn-001613

    PubMed

    researchmap

  • Predictive markers based on transcriptome modules for vinorelbine-based adjuvant chemotherapy for lung adenocarcinoma patients. International journal

    Shoko Nakasone, Ayako Suzuki, Hitomi Okazaki, Keiichi Onodera, Junko Zenkoh, Genichiro Ishii, Yutaka Suzuki, Masahiro Tsuboi, Katsuya Tsuchihara

    Lung cancer (Amsterdam, Netherlands)   158   115 - 125   2021.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVES: Microtubule inhibitors (MTIs) are widely used as anti-cancer drugs for various types of tumors. Vinorelbine, an MTI, is utilized in postoperative adjuvant chemotherapy, especially for lung adenocarcinoma. However, no molecular markers are able to identify patients for whom MTIs would be effective. In this study, we attempted to identify practical markers to predict the efficacy of MTI-based adjuvant chemotherapy. MATERIALS AND METHODS: We explored a novel combination of molecular marker candidates, based on gene expression network analysis constructed using an omics panel of 26 lung adenocarcinoma cell lines. We then applied the obtained classification method to predict the efficacy of MTI treatment in patients who received adjuvant chemotherapy. RNA sequencing (RNA-seq) analysis was conducted using surgical specimens from 24 Japanese lung adenocarcinoma patients treated postoperatively with vinorelbine. RESULTS: We identified four modules within the network with module activities that were significantly associated with sensitivity to MTIs. Two modules were associated with high sensitivity to MTIs: genes with low differentiation or transdifferentiation of lung adenocarcinomas. On the other hand, MTI-low sensitivity modules were enriched in common epithelial genes and markers of well-differentiated lung adenocarcinomas. We also classified lung adenocarcinoma cases using the module activities associated with MTI efficacy and stratify the cases with MTI resistance. CONCLUSION: We demonstrate that the constructed classification method is useful for identifying patients with MTI resistance which results in a high risk of cancer relapse.

    DOI: 10.1016/j.lungcan.2021.06.011

    PubMed

    researchmap

  • Immunological abnormalities in patients with early-onset ataxia with ocular motor apraxia and hypoalbuminemia. International journal

    Tamaki Kato, Yoshiteru Tamura, Hiroshi Matsumoto, Osamu Kobayashi, Hideaki Ishiguro, Masaya Ogawa, Koyo Tsujikawa, Yasuhiro Hasegawa, Mitsuhiro Sakamoto, Masaaki Konagaya, Hideki Houzen, Masatoshi Takagi, Kohsuke Imai, Tomohiro Morio, Akio Yokoseki, Osamu Onodera, Shigeaki Nonoyama

    Clinical immunology (Orlando, Fla.)   229   108776 - 108776   2021.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor β-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.

    DOI: 10.1016/j.clim.2021.108776

    PubMed

    researchmap

  • Pyloric-gland metaplasia may be an origin of cancer and intestinal metaplasia with possible CDX2 expression. International journal

    Kazuyoshi Yagi, Atsunori Tsuchiya, Satoru Hashimoto, Taisuke Kato, Osamu Onodera, Shuji Terai

    Gastroenterology report   9 ( 4 )   370 - 373   2021.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    DOI: 10.1093/gastro/goaa061

    Web of Science

    PubMed

    researchmap

  • The optineurin/TIA1 pathway inhibits aberrant stress granule formation and reduces ubiquitinated TDP-43. International journal

    Taichi Kakihana, Masahiko Takahashi, Yoshinori Katsuragi, Shun-Ichi Yamashita, Junya Sango, Tomotake Kanki, Osamu Onodera, Masahiro Fujii

    iScience   24 ( 7 )   102733 - 102733   2021.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease characterized by the formation of cytoplasmic ubiquitinated TDP-43 protein aggregates in motor neurons. Stress granules (SGs) are stress-induced cytoplasmic protein aggregates containing various neuropathogenic proteins, including TDP-43. Several studies have suggested that SGs are the initial site of the formation of pathogenic ubiquitinated TDP-43 aggregates in ALS neurons. Mutations in the optineurin (OPTN) and TIA1 genes are causative factors of familial ALS with TDP-43 aggregation pathology. We found that both OPTN depletion and ALS-associated OPTN mutations upregulated the TIA1 level in cells recovered from heat shock, and this upregulated TIA1 increased the amount of ubiquitinated TDP-43. Ubiquitinated TDP-43 induced by OPTN depletion was localized in SGs. Our study suggests that ALS-associated loss-of-function mutants of OPTN increase the amount of ubiquitinated TDP-43 in neurons by increasing the expression of TIA1, thereby promoting the aggregation of ubiquitinated TDP-43.

    DOI: 10.1016/j.isci.2021.102733

    PubMed

    researchmap

  • Correction to: A novel splicing variant of ANXA11 in a patient with amyotrophic lateral sclerosis: histologic and biochemical features. International journal

    Makoto Sainouchi, Yuya Hatano, Mari Tada, Tomohiko Ishihara, Shoichiro Ando, Taisuke Kato, Jun Tokunaga, Gaku Ito, Hiroaki Miyahara, Yasuko Toyoshima, Akio Yokoseki, Tetsutaro Ozawa, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Acta neuropathologica communications   9 ( 1 )   115 - 115   2021.6

     More details

  • A novel splicing variant of ANXA11 in a patient with amyotrophic lateral sclerosis: histologic and biochemical features. International journal

    Makoto Sainouchi, Yuya Hatano, Mari Tada, Tomohiko Ishihara, Shoichiro Ando, Taisuke Kato, Jun Tokunaga, Gaku Ito, Hiroaki Miyahara, Yasuko Toyoshima, Akio Yokoseki, Tetsutaro Ozawa, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Acta neuropathologica communications   9 ( 1 )   106 - 106   2021.6

     More details

  • Selective Synthesis of Acylated Cross-Benzoins from Acylals and Aldehydes via N-Heterocyclic Carbene Catalysis. International journal

    Kou Onodera, Ryo Takashima, Yumiko Suzuki

    Organic letters   23 ( 11 )   4197 - 4202   2021.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The utility of acylals as building blocks for selective cross-benzoin synthesis was explored in this study. The synthesis of α-acetoxyketones (O-acyl cross-benzoins) was achieved via selective N-heterocyclic carbene-catalyzed cross-benzoin reactions using acylals as aldehyde equivalents. Thus, the combination of ortho-substituted phenyl acylals and aromatic/aliphatic aldehydes as coupling substrates using bicyclic triazolium salts as precatalysts and potassium carbonate as a base in THF at reflux temperature selectively yielded O-acyl cross-benzoins.

    DOI: 10.1021/acs.orglett.1c01134

    PubMed

    researchmap

  • Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson's disease. International journal

    Hideaki Matsui, Junko Ito, Noriko Matsui, Tamayo Uechi, Osamu Onodera, Akiyoshi Kakita

    Nature communications   12 ( 1 )   3101 - 3101   2021.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson's disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

    DOI: 10.1038/s41467-021-23452-x

    PubMed

    researchmap

  • Differences in the isotopic signature of activated sludge in four types of advanced treatment processes at a municipal wastewater treatment plant. International journal

    Takashi Onodera, Kazuhiro Komatsu, Ayato Kohzu, Gen Kanaya, Motoyuki Mizuochi, Kazuaki Syutsubo

    Journal of environmental management   286   112264 - 112264   2021.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The natural abundance of stable isotopes is a powerful tool for evaluating biological reactions and process conditions. However, there are few stable isotope studies on the wastewater treatment process. This study carried out the first investigation on variations in natural abundance of carbon and nitrogen stable isotope ratios (δ13C and δ15N) of activated sludge in four types of advanced treatment process (extended aeration activated sludge (EAAS), aerobic-anoxic-aerobic (A2O), recycled nitrification-denitrification (RND), and modified Bardenpho (MB)) at a municipal wastewater treatment plant. The δ13C and δ15N values of influent suspended solids settled in the primary sedimentation tank (i.e., primary sludge) ranged from -25.4‰ to -24.6‰ and 0.5‰-2.9‰, respectively, during monitoring periods. The δ13C values of the activated sludge were -24.6‰ to -23.6‰ (EAAS), -25.4‰ to -24.3‰ (A2O), -25.7‰ to -24.9‰ (RND), and -25.7‰ to -24.3‰ (MB). The δ13C values of the activated sludge were similar to those of influent suspended solids. However, the δ13C values of activated sludge in EAAS was significantly higher than in A2O, RND, and MB. Meanwhile, the δ15N values of activated sludge were obviously higher than influent suspended solids; 5.8‰-7.5‰ (EAAS), 6.6‰-8.1‰ (A2O), 5.5‰-7.5‰ (RND), and 5.3‰-7.6‰ (MB). Changes in δ13C and δ15N values of the activated sludge within the treatment system were also found. These findings indicate that changes in δ13C and δ15N values of the activated sludge rely on important function for biological wastewater treatment such as nitrification, denitrification, and methane oxidation through wastewater treatment over time.

    DOI: 10.1016/j.jenvman.2021.112264

    PubMed

    researchmap

  • Evaluation of stable isotope ratios (δ15N and δ18O) of nitrate in advanced sewage treatment processes: Isotopic signature in four process types. International journal

    Takashi Onodera, Kazuhiro Komatsu, Ayato Kohzu, Gen Kanaya, Motoyuki Mizuochi, Kazuaki Syutsubo

    The Science of the total environment   762   144120 - 144120   2021.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Stable isotope ratios of nitrate are a powerful tool to evaluate aquatic environment stress from treated and untreated sewage. However, there is generally a lack of knowledge on the change in stable isotope ratios within wastewater treatment plants. We investigated nitrogen and oxygen stable isotope ratios (δ15N and δ18O) of nitrate in four types of advanced treatment processes operated in parallel; (A) extended aeration activated sludge, (B) anaerobic-anoxic-aerobic (A2O), (C) recycled nitrification-denitrification, and (D) modified Bardenpho. The results exhibited spatial variation of δ15N and δ18O for nitrate within the treatment steps. The changes in δ15N and δ18O may result from the reactor conditions (aerobic, anoxic, and anaerobic) and the order of these processes. As decreasing nitrate concentration in the anoxic stages, the δ15N/δ18O ratio for nitrate increased at a rate of 1.3 to 1.6 coupling with the reduction in the nitrate concentration in the anoxic stages. The δ15N and δ18O signatures were attributed to process performance in regard to nitrogen removal. In particular, the modified Bardenpho process has higher nitrogen removal efficiency over other processes, producing effluent with lower nitrate concentration and higher stable isotopes (δ15N: 23.6 to 25.5‰, δ18O: 2.8 to 4.5‰). We concluded that the stable isotope signatures mirrored the treatment efficiency and effluent characteristics.

    DOI: 10.1016/j.scitotenv.2020.144120

    PubMed

    researchmap

  • Heterozygous Cysteine-sparing NOTCH3 Variant p.Val237Met in a Japanese Patient with Suspected Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Case Report.

    Yuya Kano, Ikuko Mizuta, Akihiko Ueda, Hiroaki Nozaki, Keita Sakurai, Osamu Onodera, Yukio Ando, Kentaro Yamada, Hiroyuki Yuasa, Toshiki Mizuno

    Internal medicine (Tokyo, Japan)   60 ( 15 )   2479 - 2482   2021.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected of having cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) because of a family history and brain magnetic resonance imaging findings of cerebral white matter hyperintensities. The cysteine-sparing variation p.Val237Met was identified in NOTCH3. An intensive skin biopsy showed negative results (no granular osmiophilic material or positive NOTCH3 immunostaining), suggesting that the patient's definite diagnosis and pathogenicity of p.Val237Met were uncertain. We additionally reviewed previous reports of two Japanese families with p.Val237Met.

    DOI: 10.2169/internalmedicine.6096-20

    PubMed

    researchmap

  • Progressive micrographia without parkinsonism caused by autoimmune brainstem encephalitis: A case report. International journal

    Ryutaro Hanyu, Masahiro Hatakeyama, Masaki Namekawa, Yutaka Otsu, Mayura Sukegawa, Hiromi Hashida, Izumi Kawachi, Masato Kanazawa, Osamu Onodera

    Clinical neurology and neurosurgery   202   106496 - 106496   2021.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.clineuro.2021.106496

    PubMed

    researchmap

  • 頸椎除圧術後の上肢型筋萎縮索硬化症の臨床経過

    五十嵐 哲也, 渡辺 慶, 大橋 正幸, 川島 寛之, 三瓶 一弘, 五十嵐 修一, 黒羽 泰子, 小池 亮子, 石原 智彦, 大津 裕, 小野寺 理

    日本整形外科学会雑誌   95 ( 2 )   S112 - S112   2021.3

     More details

    Language:Japanese   Publisher:(公社)日本整形外科学会  

    researchmap

  • Genetic Variations and Neuropathologic Features of Patients With PRKN Mutations. International journal

    Naohiko Seike, Akio Yokoseki, Ryoko Takeuchi, Kento Saito, Hiroaki Miyahara, Akinori Miyashita, Tetsuhiko Ikeda, Izumi Aida, Takashi Nakajima, Masato Kanazawa, Masatoshi Wakabayashi, Yasuko Toyoshima, Hitoshi Takahashi, Riki Matsumoto, Tatsushi Toda, Osamu Onodera, Atsushi Ishikawa, Takeshi Ikeuchi, Akiyoshi Kakita

    Movement disorders : official journal of the Movement Disorder Society   36 ( 7 )   1634 - 1643   2021.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Mutations in PRKN are the most common cause of autosomal recessive juvenile parkinsonism. The objective of this study was to investigate the association between genotype and pathology in patients with PRKN mutations. METHODS: We performed a sequence and copy number variation analysis of PRKN, mRNA transcripts, Parkin protein expression, and neuropathology in 8 autopsied patients. RESULTS: All the patients harbored biallelic PRKN mutations. Two patients were homozygous and heterozygous, respectively, for the missense mutation p.C431F. Seven patients had exon rearrangements, including 2 patients from a single family who harbored a homozygous deletion of exon 4, and 3 patients who carried a homozygous duplication of exons 6-7, a homozygous duplication of exons 10-11, and a heterozygous duplication of exons 2-4. In the other 2 patients, we found a compound heterozygous duplication of exon 2, deletion of exon 3, and a heterozygous duplication of exon 2. However, sequencing of cDNA prepared from mRNA revealed 2 different transcripts derived from triplication of exon 2 and deletion of exons 2-3 and from duplication of exons 2-4 and deletion of exons 3-4. Western blotting and immunohistochemistry revealed faint or no expression of Parkin in their brains. In the substantia nigra pars compacta, a subfield-specific pattern of neuronal loss and mild gliosis were evident. Lewy bodies were found in 3 patients. Peripheral sensory neuronopathy was a feature. CONCLUSIONS: Genomic and mRNA analysis is needed to identify the PRKN mutations. Variable mutations may result in no or little production of mature Parkin and the histopathologic features may be similar.

    DOI: 10.1002/mds.28521

    PubMed

    researchmap

  • Corrigendum: HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade. International journal

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in neurology   12   756038 - 756038   2021

     More details

    Language:English  

    [This corrects the article DOI: 10.3389/fneur.2019.00693.].

    DOI: 10.3389/fneur.2021.756038

    PubMed

    researchmap

  • Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review. International journal

    Yutaka Otsu, Masaki Namekawa, Masafumi Toriyabe, Itaru Ninomiya, Masahiro Hatakeyama, Masahiro Uemura, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

    Journal of the neurological sciences   419   117217 - 117217   2020.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma. AIM: To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS. METHODS: A literature review was performed using PubMed and the ClinicalTrials.gov database. RESULTS: Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected. CONCLUSION: To fully utilize the easily accessible drug-tPA-and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents.

    DOI: 10.1016/j.jns.2020.117217

    PubMed

    researchmap

  • Progressive supranuclear palsy: Neuropathology of patients with a short disease duration due to unexpected death International journal

    Lu Zhang, Yasuko Toyoshima, Akari Takeshima, Hiroshi Shimizu, Itsuro Tomita, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    NEUROPATHOLOGY   41 ( 3 )   174 - 182   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Progressive supranuclear palsy (PSP) presents with a wide variety of signs/symptoms, making early initial diagnosis difficult. We investigated the clinical and neuropathological features of five patients with autopsy-proven PSP of short duration, ranging from 11 to 41 months (average, 26.2 months) due to unexpected death, focusing particularly on the distribution and severity of neuronal loss as well as neuronal and glial tau pathology in the affected brain. Clinical features were studied retrospectively through careful review of the medical records, and neuropathological examinations were carried out, along with tau immunohistochemistry using a monoclonal antibody AT8. These patients were diagnosed as having probable PSP (n = 4) and suggestive PSP (n = 1), respectively. In all cases, neuronal loss was evident in the substantia nigra, subthalamic nucleus, globus pallidus, and locus ceruleus. AT8-identified tau lesions, that is, pretangles/neurofibrillary tangles (PTs/NFTs), tufted astrocytes (TAs), and coiled bodies/neuropil threads (CBs/NTs), were distributed widely in the brain regions, especially in patients with longer disease duration. All cases showed variation in the regional tau burden among PTs/NFTs, TAs, and CBs/NTs. There was also a tendency for tau deposition to be more predominant in neuronal cells in the brainstem and cerebellum and in glial cells in the cerebral cortex and subcortical gray matter. These findings suggest that in PSP, the initial signs/symptoms are associated with degeneration and subsequent death of neurons with pathological tau deposition, and that the tau deposition in neuronal cells is independent of that in glial cells.

    DOI: 10.1111/neup.12707

    Web of Science

    PubMed

    researchmap

  • Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island. International journal

    Kei Takamisawa, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kazutoshi Nakamura, Osamu Onodera, Takeshi Momotsu, Naoto Endo, Kenji Sato, Ichiei Narita, Hiromasa Yoshie, Koichi Tabeta

    Heliyon   6 ( 11 )   e05531   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Background: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. Methods: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. Results: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. Conclusions: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

    DOI: 10.1016/j.heliyon.2020.e05531

    PubMed

    researchmap

  • 筋萎縮性側索硬化症の確定診断までの時間に与える、初診科、発症部位の検討

    大津 裕, 小池 佑佳, 石原 智彦, 小野寺 理

    臨床神経学   60 ( Suppl. )   S380 - S380   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経疾患・精神疾患の鑑別における血漿炎症性サイトカインの有用性

    樋口 陽, 春日 健作, 徳武 孝允, 宮下 哲典, 茂木 崇治, 福井 直樹, 横山 裕一, 染矢 俊幸, 小野寺 理, 池内 健

    臨床神経学   60 ( Suppl. )   S377 - S377   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 日本におけるSOD1遺伝子変異陽性筋萎縮性側索硬化症患者の臨床的特徴

    中村 亮一, 熱田 直樹, 藤内 玄規, 林 直毅, 勝野 雅央, 和泉 唯信, 金井 数明, 服部 信孝, 谷口 彰, 森田 光哉, 狩野 修, 澁谷 和幹, 桑原 聡, 鈴木 直輝, 青木 正志, 阿部 康二, 石原 智彦, 小野寺 理, 梶 龍兒, 祖父江 元

    臨床神経学   60 ( Suppl. )   S381 - S381   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CADASIL原因遺伝子NOTCH3のシステイン非関連variant p.Val237Metの病的意義の検討

    水田 依久子, 加納 裕也, 植田 明彦, 野崎 洋明, 櫻井 圭太, 小野寺 理, 安東 由喜雄, 湯浅 浩之, 水野 敏樹

    臨床神経学   60 ( Suppl. )   S421 - S421   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CADASIL原因遺伝子NOTCH3のシステイン非関連variant p.Val237Metの病的意義の検討

    水田 依久子, 加納 裕也, 植田 明彦, 野崎 洋明, 櫻井 圭太, 小野寺 理, 安東 由喜雄, 湯浅 浩之, 水野 敏樹

    臨床神経学   60 ( Suppl. )   S421 - S421   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症における脳脊髄液中NG2とα-シヌクレインの検討

    徳武 孝允, 春日 健作, 月江 珠緒, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    臨床神経学   60 ( Suppl. )   S433 - S433   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 散発性ALSの137症例における剖検物のエキソーム分析(Exome analysis in 137 autopsied sporadic ALS cases)

    Ishihara Tomohiko, Hatano Yuya, Yokoseki Akio, Tada Mari, Nakajima Takashi, Koike Ryoko, Kakita Akiyoshi, Onodera Osamu

    臨床神経学   60 ( Suppl. )   S309 - S309   2020.11

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • ALS剖検例に関するテキストマイニングとエキソーム分析を用いたALSの新規候補遺伝子の探索(Search for new candidate genes for ALS by textmining and exome analysis of autopsy cases)

    Hatano Yuya, Ishihara Tomohiko, Yokoseki Akio, Tada Mari, Kakita Akiyoshi, Okuda Shujiro, Onodera Osamu

    臨床神経学   60 ( Suppl. )   S324 - S324   2020.11

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • [Cell Therapy Using Peripheral Mononuclear Cells Preconditioned by Oxygen-Glucose Deprivation for Ischemic Stroke].

    Masahiro Hatakeyama, Itaru Ninomiya, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

    Brain and nerve = Shinkei kenkyu no shinpo   72 ( 10 )   1097 - 1103   2020.10

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Many studies in recent years have reported cell therapies using embryonic stem cells, induced pluripotent stem cells, and bone marrow-derived mononuclear cells for cerebral ischemia. However, obtaining these cells is challenging, and these cell therapies require complicated procedures to prepare cells for administration. Notably, peripheral blood mononuclear cells (PBMCs) are a useful cell source for clinical applications because cell collection is easier. In this review, we report the therapeutic effects of PBMCs preconditioned by oxygen-glucose deprivation (OGD-PBMCs) on cerebral ischemia. Cell therapies using tissue-protective OGD-PBMCs might be a simple and ideal therapeutic strategy against ischemic stroke.

    DOI: 10.11477/mf.1416201655

    PubMed

    researchmap

  • 本邦におけるCADASILの全国調査と多施設データベースの構築

    新堂 晃大, 田部井 賢一, 谷口 彰, 小野寺 理, 安東 由喜雄, 卜部 貴夫, 北川 一夫, 羽生 春夫, 平野 照之, 脇田 英明, 福山 秀直, 鍵村 達夫, 宮本 恵宏, 竹上 未紗, 水田 依久子, 猪原 匡史, 水野 敏樹, 冨本 秀和

    Dementia Japan   34 ( 4 )   491 - 491   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 本邦におけるCADASILの全国調査と多施設データベースの構築

    新堂 晃大, 田部井 賢一, 谷口 彰, 小野寺 理, 安東 由喜雄, 卜部 貴夫, 北川 一夫, 羽生 春夫, 平野 照之, 脇田 英明, 福山 秀直, 鍵村 達夫, 宮本 恵宏, 竹上 未紗, 水田 依久子, 猪原 匡史, 水野 敏樹, 冨本 秀和

    Dementia Japan   34 ( 4 )   491 - 491   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 実は見逃されている血管性認知症の危険因子

    山下 徹, 野崎 洋明, 涌谷 陽介, 田所 功, 野村 恵美, 菱川 望, 武本 麻美, 太田 康之, 小野寺 理, 阿部 康二

    Dementia Japan   34 ( 4 )   493 - 493   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis. International journal

    Ryoichi Nakamura, Kazuharu Misawa, Genki Tohnai, Masahiro Nakatochi, Sho Furuhashi, Naoki Atsuta, Naoki Hayashi, Daichi Yokoi, Hazuki Watanabe, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Kazuaki Kanai, Nobutaka Hattori, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Kazumoto Shibuya, Satoshi Kuwabara, Naoki Suzuki, Masashi Aoki, Yasuyuki Ohta, Toru Yamashita, Koji Abe, Rina Hashimoto, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Yohei Okada, Tomohiko Ishihara, Osamu Onodera, Kenji Nakashima, Ryuji Kaji, Yoichiro Kamatani, Shiro Ikegawa, Yukihide Momozawa, Michiaki Kubo, Noriko Ishida, Naoko Minegishi, Masao Nagasaki, Gen Sobue

    Communications biology   3 ( 1 )   526 - 526   2020.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10-8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10-4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10-11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.

    DOI: 10.1038/s42003-020-01251-2

    PubMed

    researchmap

  • クエチアピン単剤化により精神症状と運動症状が改善したハンチントン病による認知症の1例

    宮下 真子, 渡部 雄一郎, 本郷 祥子, 小池 直人, 佐治 越爾, 深石 翔, 三上 剛明, 小野寺 理, 染矢 俊幸

    精神神経学雑誌   ( 2020特別号 )   S313 - S313   2020.9

     More details

    Language:Japanese   Publisher:(公社)日本精神神経学会  

    researchmap

  • Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review. Reviewed International journal

    Masahiro Hatakeyama, Itaru Ninomiya, Yutaka Otsu, Kaoru Omae, Yasuko Kimura, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata, Masato Kanazawa

    International journal of molecular sciences   21 ( 17 )   2020.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy; they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

    DOI: 10.3390/ijms21176194

    PubMed

    researchmap

  • Novel CHP1 mutation in autosomal-recessive cerebellar ataxia: autopsy features of two siblings. Reviewed International journal

    Rie Saito, Norikazu Hara, Mari Tada, Yoshiaki Honma, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Acta neuropathologica communications   8 ( 1 )   134 - 134   2020.8

     More details

  • [Dural arteriovenous fistula causing complex visual hallucinations without an anopsia]. Reviewed

    Shingo Koide, Masahiro Hatakeyama, Masahiro Uemura, Bumpei Kikuchi, Hitoshi Hasegawa, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   60 ( 6 )   425 - 428   2020.6

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report the case of a 76-year-old woman who presented with recurrent episodes of complex visual hallucinations in her right visual field without an anopsia. The electroencephalogram showed sharp transients in the left parietotemporal region with phase reversals at T5 and P3. FLAIR MRI revealed hyperintense lesions in the left temporo-occipital lobe, located mainly in the left inferior temporal lobe. Cerebral angiography revealed an arteriovenous shunt from the left occipital artery to the left transverse sinus with cortical venous reflux. The complex visual hallucinations were resolved after transarterial embolization. We therefore hypothesize that this patient's complex visual hallucinations were caused by epileptic seizures or changes in cortical blood flow caused by the cortical venous reflux from the arteriovenous fistula. In general, epileptic hallucinations expand into the bilateral visual field. We reveal that in rare cases, complex visual hallucinations can also be limited to the unilateral visual field without an anopsia. Additionally, we reveal that a dural arteriovenous fistula can cause visual hallucinations without hemianopia.

    DOI: 10.5692/clinicalneurol.60.cn-001371

    PubMed

    researchmap

  • Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12. Reviewed International journal

    Rie Saito, Hiroshi Shimizu, Takeshi Miura, Norikazu Hara, Naomi Mezaki, Yo Higuchi, Akinori Miyashita, Izumi Kawachi, Kazuhiro Sanpei, Yoshiaki Honma, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Acta neuropathologica communications   8 ( 1 )   75 - 75   2020.6

     More details

  • Refractory Myositis Affecting the Intrinsic Muscles of the Hand. Reviewed

    Kosei Nakamura, Akihiro Sugai, Etsuji Saji, Kensaku Kasuga, Osamu Onodera

    Internal medicine (Tokyo, Japan)   59 ( 9 )   1211 - 1214   2020.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Myositis generally affects the proximal muscles. However, we herein report a case of a 48-year-old woman with intractable myositis affecting the intrinsic muscles of the hands. Her myositis, which developed in childhood, was refractory to treatment with steroids and several immunosuppressants, causing walking disability. After experiencing pain and swelling in the hands for six months, she was diagnosed with myositis of the intrinsic muscles of the hands and tested positive for the anti-signal recognition particle antibody. Intravenous immunoglobulin therapy improved the myositis of the hands. This case suggests that inflammation caused by intractable myositis can extend to the hands.

    DOI: 10.2169/internalmedicine.3773-19

    PubMed

    researchmap

  • [Amyloid β-related angiitis presenting extensive brain involvement without detection of hemorrhagic lesions: A case report]. Reviewed

    Yuya Hatano, Akihiro Sugai, Takuma Yamagishi, Akihiro Nakajima, Akiyoshi Kakita, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   60 ( 3 )   187 - 192   2020.3

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    In amyloid β-related angiitis, cortical or subcortical microbleeding or cortical superficial siderosis supports clinical diagnosis. However, here we present a 75-year-old female case of amyloid β-related angiitis that did not initially show these lesions. The patient developed right homonymous hemianopia and aphasia, and subsequently became comatose. Her brain lesions progressed extensively from the left occipital lobe to the bilateral cerebral hemispheres, with diffused leptomeningeal lesions and scattered DWI high-intensity lesions. After pathological diagnosis, steroid treatment improved her symptoms as well as imaging findings. No hemorrhagic lesions were detected in the T2*-weighted imaging performed before treatment. However, susceptibility-weighted imaging performed after treatment showed a number of lesions with microbleeding. The clinical features of amyloid β-related angiitis that do not show hemorrhagic lesions at onset should be investigated for rapid therapeutic intervention in the future.

    DOI: 10.5692/clinicalneurol.cn-001340

    PubMed

    researchmap

  • 新規抗てんかん薬トピラマートのラット骨代謝に及ぼす影響

    神田 循吉, 出雲 信夫, 古川 恵, 島倉 剛俊, 山本 智章, 小野寺 憲治, 若林 広行

    日本薬学会年会要旨集   140年会   27Q - am056   2020.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • [Molecular mechanism of amyotrophic lateral sclerosis (ALS) from the viewpoint of the formation and degeneration of transactive response DNA-binding protein 43 kDa (TDP-43) inclusions]. Reviewed

    Sou Kasahara, Tomohiko Ishihara, Yuka Koike, Akihiro Sugai, Osamu Onodera

    Rinsho shinkeigaku = Clinical neurology   60 ( 2 )   109 - 116   2020.2

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Sporadic amyotrophic lateral sclerosis (SALS) and many cases of familial ALS (FALS) demonstrate cytoplasmic transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusion bodies. Thus, TDP-43 plays a vital role in ALS pathogenesis. Functional analysis of the ALS causative genes advanced the elucidation of the mechanism associated with the formation and degradation of TDP-43 aggregates. Stress granules, which are non-membranous organelles, are attracting attention as sites of aggregate formation, with involvement of FUS and C9orf72. Concurrently, ALS causative genes related to the ubiquitin-proteasome and autophagy systems, which are aggregate degradation mechanisms, have also been reported. Therefore, therapeutic research based on the molecular pathology common to SALS and FALS has been advanced.

    DOI: 10.5692/clinicalneurol.cn-001362

    PubMed

    researchmap

  • Hemorrhagic cerebral small vessel disease caused by a novel mutation in 3' UTR of collagen type IV alpha 1. Reviewed International journal

    Naoko Sakai, Masahiro Uemura, Taisuke Kato, Hiroaki Nozaki, Akihide Koyama, Shouichirou Ando, Hiroyuki Kamei, Motohiro Kato, Osamu Onodera

    Neurology. Genetics   6 ( 1 )   e383   2020.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1212/NXG.0000000000000383

    PubMed

    researchmap

  • Transactive response DNA-binding protein 43kDa(TDP-43)凝集体の形成と分解からみたamyotrophic lateral sclerosis(ALS)の分子機構 Reviewed

    笠原 壮, 石原 智彦, 小池 佑佳, 須貝 章弘, 小野寺 理

    臨床神経学   60 ( 2 )   109 - 116   2020.2

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    孤発性筋萎縮性側索硬化症(sporadic amyotrophic lateral sclerosis;SALS)、および多くの家族性ALS(familial ALS;FALS)において、神経細胞質内transactive response DNA-binding protein 43kDa(TDP-43)陽性の封入体を認める。この事実からTDP-43は本症の根幹に関わる分子である。ALS病因遺伝子の機能解析から、TDP-43の病的凝集体形成/分解に関わる発症メカニズムの解明が進められている。凝集体形成の場として、非膜性構造であるストレス顆粒が注目されており、FUSやC9orf72の関与が示されている。一方、凝集体分解機構であるユビキチン-プロテアソーム系、オートファジー系に関わるALS病因遺伝子も報告されている。SALSおよびFALSに共通する分子病態に対する治療研究が進められている。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200213270001&doc_link_id=130007802650&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007802650&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Frequencies of Hereditary Cerebral Small Vessel Diseases Among Patients With Adult-Onset Leukoencephalopathy

    Masahiro Uemura, Hiroaki Nozaki, Naoko Sakai, Shouichirou Ando, Masato Kanazawa, Hajime Kondo, Akira Iwanaga, Hiroyuki Murota, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    STROKE   51   2020.2

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Role of RNF213 p.4810K variant in the development of intracranial arterial disease in patients treated with nilotinib. Reviewed International journal

    Masahiro Uemura, Masato Kanazawa, Takuma Yamagishi, Takahiro Nagai, Mami Takahashi, Shingo Koide, Masayoshi Tada, Junsuke Shimbo, Aiko Isami, Kunihiko Makino, Masayoshi Masuko, Kouji Nikkuni, Kouichirou Okamoto, Shuichi Igarashi, Kenichi Morita, Osamu Onodera

    Journal of the neurological sciences   408   116577 - 116577   2020.1

     More details

  • Progressive Supranuclear Palsy with Predominant Cerebellar Ataxia. Reviewed International journal

    Shoichiro Ando, Masato Kanazawa, Osamu Onodera

    Journal of movement disorders   13 ( 1 )   20 - 26   2020.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Progressive supranuclear palsy (PSP) is characterized by supranuclear gaze palsy, dystonic rigidity of the neck and upper trunk, frequent falls and mild cognitive impairment. Cerebellar ataxia is one of the exclusion criteria given by the National Institute of Neurological Disorders and Stroke and the Society for Progressive Supranuclear Palsy. As a result, pathologically proven PSP patients exhibiting cerebellar ataxia have often been misdiagnosed with spinocerebellar degeneration, specifically multiple system atrophy with predominant cerebellar ataxia (MSA-C). However, more recently, it has been recognized that patients with PSP can present with truncal and limb ataxia as their initial symptom and/or main manifestation. These patients can be classified as having PSP with predominant cerebellar ataxia (PSP-C), a new subtype of PSP. Since the development of this classification, patients with PSP-C have been identified primarily in Asian countries, and it has been noted that this condition is very rare in Western communities. Furthermore, the clinical features of PSP-C have been identified, enabling it to be distinguished from other subtypes of PSP and MSA-C. In this review, we describe the clinical and neuropathological features of PSP-C. The hypothesized pathophysiology of cerebellar ataxia in PSP-C is also discussed.

    DOI: 10.14802/jmd.19061

    PubMed

    researchmap

  • Excessive Production of Transforming Growth Factor β1 Causes Mural Cell Depletion From Cerebral Small Vessels. Reviewed International journal

    Taisuke Kato, Yumi Sekine, Hiroaki Nozaki, Masahiro Uemura, Shoichiro Ando, Sachiko Hirokawa, Osamu Onodera

    Frontiers in aging neuroscience   12   151 - 151   2020

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    It is increasingly becoming apparent that cerebrovascular dysfunction contributes to the pathogenic processes involved in vascular dementia, Alzheimer's disease, and other neurodegenerative disorders. Under these pathologic conditions, the degeneration of cerebral blood vessels is frequently accompanied by a loss of mural cells from the vascular walls. Vascular mural cells play pivotal roles in cerebrovascular functions, such as regulation of cerebral blood flow and maintenance of the blood-brain barrier (BBB). Therefore, cerebrovascular mural cell impairment is involved in the pathophysiology of vascular-related encephalopathies, and protecting these cells is essential for maintaining brain health. However, our understanding of the molecular mechanism underlying mural cell abnormalities is incomplete. Several reports have indicated that dysregulated transforming growth factor β (TGFβ) signaling is involved in the development of cerebral arteriopathies. These studies have specifically suggested the involvement of TGFβ overproduction. Although cerebrovascular toxicity via vascular fibrosis by extracellular matrix accumulation or amyloid deposition is known to occur with enhanced TGFβ production, whether increased TGFβ results in the degeneration of vascular mural cells in vivo remains unknown. Here, we demonstrated that chronic TGFβ1 overproduction causes a dropout of mural cells and reduces their coverage on cerebral vessels in both smooth muscle cells and pericytes. Mural cell degeneration was also accompanied by vascular luminal dilation. TGFβ1 overproduction in astrocytes significantly increased TGFβ1 content in the cerebrospinal fluid (CSF) and increased TGFβ signaling-regulated gene expression in both pial arteries and brain capillaries. These results indicate that TGFβ is an important effector that mediates mural cell abnormalities under pathological conditions related to cerebral arteriopathies.

    DOI: 10.3389/fnagi.2020.00151

    PubMed

    researchmap

  • A Nationwide Survey and Multicenter Registry-Based Database of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy in Japan. Reviewed International journal

    Akihiro Shindo, Ken-Ichi Tabei, Akira Taniguchi, Hiroaki Nozaki, Osamu Onodera, Akihiko Ueda, Yukio Ando, Takao Urabe, Kazumi Kimura, Kazuo Kitagawa, Haruo Hanyu, Teruyuki Hirano, Hideaki Wakita, Hidenao Fukuyama, Tatsuo Kagimura, Yoshihiro Miyamoto, Misa Takegami, Satoshi Saito, Akiko Watanabe-Hosomi, Ikuko Mizuta, Masafumi Ihara, Toshiki Mizuno, Hidekazu Tomimoto

    Frontiers in aging neuroscience   12   216 - 216   2020

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Objectives: Clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) include migraine, recurrent stroke, white matter lesions, and vascular dementia. CADASIL is one of the most common hereditary cerebral small vessel diseases. Clinical presentation of CADASIL varies and a racial gap may exist between the Asian and Caucasian populations. This is the first nationwide epidemiological survey which aimed to elucidate the clinical features of CADASIL in Japan. Moreover, the registration database of CADASIL was constructed. Methods: Subjects included CADASIL patients who visited the hospitals (totally 1,448 hospitals) certified by the Japanese Society of Neurology and/or Japan Stroke Society in 2016. This study consisted of a two-step survey; patients with CADASIL were identified genetically by the first questionnaire, and their clinical features were assessed by the second questionnaire. Selected 6 hospitals registered the data of all CADASIL patients using a Research Electronic Data Capture (REDCap) system for the second questionnaire. Results: Based on the criteria, 88 patients (50 male and 38 female) with CADASIL were enrolled. The mean age of symptom onset was 49.5 years. Sixteen (18.2%) patients had an elderly onset (>60 years). Thirteen patients (13.6%) had history of migraine with aura and 33 patients (37.5%) had vascular risk factor(s). From among the 86 patients who were examined using magnetic resonance imaging, abnormal deep white matter lesions were detected in 85 patients (98.8%), WMLs extending to anterior temporal pole in 73 patients (84.9%), and cerebral microbleeds in 41 patients (47.7%). Anti-platelet therapy was received by 65 patients (73.9%). Thirty-eight patients (43.2%) underwent treatment with lomerizine hydrochloride. Thirty-four different mutations of NOTCH3 were found in exons 2, 3, 4, 5, 6, 8, 11, 14, and 19. Most of the mutations existed in exon 4 (n = 44, 60.3%). The prevalence rate of CADASIL was 1.20 to 3.58 per 100,000 adults in Japan. Conclusion: This questionnaire-based study revealed clinical features and treatment status in Japanese CADASIL patient, although it may not be an exhaustive search. We have constructed the REDCap database for these CADASIL patients.

    DOI: 10.3389/fnagi.2020.00216

    PubMed

    researchmap

  • Publisher Correction: A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation. Reviewed International journal

    Masahiro Hatakeyama, Masato Kanazawa, Itaru Ninomiya, Kaoru Omae, Yasuko Kimura, Tetsuya Takahashi, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata

    Scientific reports   9 ( 1 )   19913 - 19913   2019.12

     More details

    Language:English  

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    DOI: 10.1038/s41598-019-55308-2

    PubMed

    researchmap

  • TAF15が主要に蓄積したFET病理を伴う筋萎縮性側索硬化症 剖検例の臨床病理学的特徴(Amsotrophic lateral sclerosis with TAF15-predominant FET pathology: clinicopathologic features of an autopsied patient)

    Cui Bo, Tada Mari, Hatano Yuya, Takeshima Akari, Ishihara Tomohiko, Sugai Akihiro, Tokutake Takayoshi, Kanazawa Masato, Onodera Osamu, Kakita Akiyoshi

    新潟医学会雑誌   133 ( 11-12 )   391 - 391   2019.12

  • A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation. Reviewed International journal

    Masahiro Hatakeyama, Masato Kanazawa, Itaru Ninomiya, Kaoru Omae, Yasuko Kimura, Tetsuya Takahashi, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata

    Scientific reports   9 ( 1 )   16819 - 16819   2019.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.

    DOI: 10.1038/s41598-019-53418-5

    PubMed

    researchmap

  • [Molecular Pathogenesis of Amyotrophic Lateral Sclerosis]. Reviewed

    Shintaro Tsuboguchi, Tomohiko Ishihara, Akihiro Sugai, Akio Yokoseki, Osamu Onodera

    Brain and nerve = Shinkei kenkyu no shinpo   71 ( 11 )   1183 - 1189   2019.11

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) has been studied through analysis of the function of the protein produced by the causative genes of familial ALS. The products of these genes are classified as RNA binding proteins, or proteins related to proteolytic systems. However, most case of familial ALS, and sporadic ALS show TAR DNA binding protein-43 (TDP-43) immune-positive cytoplasmic inclusions. Therefore, the molecular mechanism of formation of TDP-43 inclusions and dysfunction caused by TDP-43 inclusions has been studied. As for the mechanism of inclusion formation, non-membrane organelle formation by liquid-liquid phase separation (LLPS) is important. The ubiquitin-proteasome and autophagy systems are important for the degradation of these inclusions. Several genes associated with these systems have been identified as causative genes for ALS. The formation of cytoplasmic inclusions results in the loss of TDP-43 from the nucleus, resulting in abnormalities in RNA metabolism, through the alteration of spliceosomes and Gemini of coiled bodies. Furthermore, in ALS, the regulation of TDP-43 mRNA/protein expression levels has failed. Failure of the autoregulation system facilitates TDP-43 inclusion formation. Development of treatments for ALS based on these elucidated molecular mechanisms is desirable.

    DOI: 10.11477/mf.1416201428

    PubMed

    researchmap

  • Shrinkage of the myenteric neurons of the small intestine in patients with multiple system atrophy. Reviewed International journal

    Tetsutaro Ozawa, Hiroshi Shimizu, Hideaki Matsui, Osamu Onodera, Akiyoshi Kakita

    Autonomic neuroscience : basic & clinical   221   102583 - 102583   2019.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    This study aimed to determine whether enteric neurons are involved in multiple system atrophy (MSA). Four-μm-thick slices of small intestine were prepared from 10%-formalin-fixed and paraffin-embedded materials obtained from autopsied cases. Enteric neurons were stained using an anti-peripherin antibody. Immunostaining of phosphorylated α-synuclein was also performed. Areas of the cytoplasm and nucleus that showed nucleoli were measured using computer software. Both areas of myenteric neurons were significantly smaller in MSA cases (n = 3) than in control subjects (n = 3) (P < 0.0001); however, no deposits of phosphorylated α-synuclein were observed. These findings suggest that myenteric neurons in MSA are affected independent of α-synuclein accumulation.

    DOI: 10.1016/j.autneu.2019.102583

    PubMed

    researchmap

  • 【ALS 2019】TDP-43封入体から解くALSの分子病態 Reviewed

    坪口 晋太朗, 石原 智彦, 須貝 章弘, 横関 明男, 小野寺 理

    BRAIN and NERVE: 神経研究の進歩   71 ( 11 )   1183 - 1189   2019.11

     More details

    Language:Japanese   Publisher:(株)医学書院  

    <文献概要>TDP-43蛋白質の封入体形成機構は,筋萎縮性側索硬化症(ALS)の主要な分子病態機序である。ALS原因遺伝子の機能解析から,TDP-43封入体形成にはストレス顆粒形成,蛋白質分解機構,TDP-43蛋白質の自己調節機構の破綻などが関わることが見出された。これらの解明された分子病態に基づく,ALS治療方法の確立が期待される。

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04871&link_issn=&doc_id=20191114320010&doc_link_id=40022086926&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40022086926&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • HTRA1 Disorder

    Onodera O, Nozaki H, Fukutake T

    2019.11

     More details

    Publishing type:Research paper (scientific journal)  

    PubMed

    researchmap

  • PSP症例におけるPSP評価尺度と臨床診断の縦断研究(Longitudinal study of PSP rating scale and clinical diagnosis in PSP cases)

    Takigawa Hiroshi, Ikeuchi Takeshi, Aiba Ikuko, Morita Mitsuya, Onodera Osamu, Shimohata Takayoshi, Tokuda Takahiko, Murayama Shigeo, Hasegawa Kazuko, Kowa Hisanori, Tokumaru Aya M., Hanajima Ritsuko, Nakashima Kenji, JALPAC study group

    臨床神経学   59 ( Suppl. )   S245 - S245   2019.11

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • ALS患者の生存期間に与える非侵襲的換気補助療法の影響 レジストリを用いた解析

    熱田 直樹, 横井 大知, 平川 晃弘, 林 直毅, 中村 良一, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 狩野 修, 桑原 聡, 青木 正志, 金井 数明, 小野寺 理, 梶 龍兒, 祖父江 元, JaCALS

    臨床神経学   59 ( Suppl. )   S358 - S358   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • APP処理に対し時間・程度依存性の神経細胞活性化が及ぼす影響(Time- and extent- dependent effect of neuronal activation on APP processing)

    Ishiguro Takanobu, Kasuga Kensaku, Saito Kento, Mezaki Naomi, Miura Takeshi, Tokutake Takayoshi, Onodera Osamu, Ikeuchi Takeshi

    臨床神経学   59 ( Suppl. )   S411 - S411   2019.11

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • Phosphorylated TDP-43 aggregates in skeletal and cardiac muscle are a marker of myogenic degeneration in amyotrophic lateral sclerosis and various conditions. Reviewed International journal

    Fumiaki Mori, Mari Tada, Tomoya Kon, Yasuo Miki, Kunikazu Tanji, Hidekachi Kurotaki, Masahiko Tomiyama, Tomohiko Ishihara, Osamu Onodera, Akiyoshi Kakita, Koichi Wakabayashi

    Acta neuropathologica communications   7 ( 1 )   165 - 165   2019.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized pathologically by the occurrence of phosphorylated TDP-43 (pTDP-43)-immunoreactive neuronal and glial inclusions in the central nervous system. Recent studies have shown that pTDP-43 aggregates also occur in the skeletal muscles in a certain proportion of ALS patients. AIM: The aim of this study was to clarify the distribution and incidence of pTDP-43 aggregates in the skeletal and cardiac muscles of patients with ALS, and also those of patients with neuromuscular diseases (NMDs) and non-NMDs. MATERIAL AND METHODS: Five regions of muscle (tongue, cervical muscle, diaphragm, iliopsoas muscle and heart) were examined histologically and immunohistochemically in patients with ALS (n = 30), NMDs (n = 13) and non-NMDs (n = 7). RESULTS: Two types of pTDP-43 aggregates were distinguishable morphologically: dense filamentous and short linear inclusions. These inclusions were found in at least one of the five muscle regions in all 30 cases of ALS; skeletal muscles in 28 cases and myocardium in 12. pTDP-43 aggregates were also found in 9 of 13 patients with NMDs, including myositis, muscular dystrophy and mitochondrial myopathy, as well as in 3 of 7 patients with non-NMDs. In ALS, pTDP-43 aggregates were most frequent in the diaphragm (19 cases). The mean density of pTDP-43 aggregates in ALS was significantly higher than that in NMDs and non-NMDs. In contiguous sections stained with hematoxylin and eosin and anti-pTDP-43, muscle fibers with dense filamentous inclusions demonstrated single-fiber atrophy with vacuolar degeneration. CONCLUSION: The present findings indicate that pTDP-43 aggregates in skeletal and cardiac muscle are a myogenic pathological marker in multiple diseases including ALS.

    DOI: 10.1186/s40478-019-0824-1

    PubMed

    researchmap

  • Morphological characterisation of glial and neuronal tau pathology in globular glial tauopathy (Types II and III). Reviewed International journal

    H Tanaka, Y Toyoshima, S Kawakatsu, R Kobayashi, O Yokota, S Terada, S Kuroda, T Miura, Y Higuchi, H Otsu, K Sanpei, K Otani, T Ikeuchi, O Onodera, A Kakita, H Takahashi

    Neuropathology and applied neurobiology   2019.10

     More details

    Language:English  

    AIMS: Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised neuropathologically by tau-positive globular glial inclusions (GGIs), namely, globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). Occurrence of tau-positive neuronal cytoplasmic inclusions (NCIs) is also a feature. GGT is classified into three pathological subtypes (Types I, II and III). We studied the tau pathology in 6 cases of GGT (Type II, n = 3; Type III, n = 3), with special reference to GAIs and NCIs. METHODS: Neuropathological examinations were conducted, along with immunohistochemistry, morphometry and three-dimensional imaging, and biochemical and genetic analysis of tau. RESULTS: The cortical GAIs in Type II and those in Type III were distinguishable from each other. In the motor cortex, GAIs were much more numerous in Type III than in Type II. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than in Type II. NCIs were divisible into three subgroups in terms of shape: diffuse granular, thick cord-like, and round/horseshoe-shaped structures. In all cases, NCIs were a feature of the upper and lower motor neurons. Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. CONCLUSIONS: These findings, which characterised GAIs and NCIs, indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

    DOI: 10.1111/nan.12581

    PubMed

    researchmap

  • Spinocerebellar Ataxia Type 17

    Toyoshima Y, Onodera O, Yamada M, Tsuji S, Takahashi H

    2019.9

     More details

    Publishing type:Research paper (scientific journal)  

    PubMed

    researchmap

  • Ectopic Expression Induces Abnormal Somatodendritic Distribution of Tau in the Mouse Brain. Reviewed International journal

    Atsuko Kubo, Shouyou Ueda, Ayaka Yamane, Satoko Wada-Kakuda, Mai Narita, Makoto Matsuyama, Akane Nomori, Akihiko Takashima, Taisuke Kato, Osamu Onodera, Motohito Goto, Mamoru Ito, Takami Tomiyama, Hiroshi Mori, Shigeo Murayama, Yasuo Ihara, Hiroaki Misonou, Tomohiro Miyasaka

    The Journal of neuroscience : the official journal of the Society for Neuroscience   39 ( 34 )   6781 - 6797   2019.8

     More details

    Language:English  

    Tau is a microtubule (MT)-associated protein that is localized to the axon. In Alzheimer's disease, the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. To investigate how this mislocalization occurs, we recently developed immunohistochemical tools that can separately detect endogenous mouse and exogenous human tau with high sensitivity, which allows us to visualize not only the pathological but also the pre-aggregated tau in mouse brain tissues of both sexes. Using these antibodies, we found that in tau-transgenic mouse brains, exogenous human tau was abundant in dendrites and somata even in the presymptomatic period, whereas the axonal localization of endogenous mouse tau was unaffected. In stark contrast, exogenous tau was properly localized to the axon in human tau knock-in mice. We tracked this difference to the temporal expression patterns of tau. Endogenous mouse tau and exogenous human tau in human tau knock-in mice exhibited high expression levels during the neonatal period and strong suppression into the adulthood. However, human tau in transgenic mice was expressed continuously and at high levels in adult animals. These results indicated the uncontrolled expression of exogenous tau beyond the developmental period as a cause of mislocalization in the transgenic mice. Superresolution microscopic and biochemical analyses also indicated that the interaction between MTs and exogenous tau was impaired only in the tau-transgenic mice, but not in knock-in mice. Thus, the ectopic expression of tau may be critical for its somatodendritic mislocalization, a key step of the tauopathy.SIGNIFICANCE STATEMENT Somatodendritic localization of tau may be an early step leading to the neuronal degeneration in tauopathies. However, the mechanisms of the normal axonal distribution of tau and the mislocalization of pathological tau remain obscure. Our immunohistochemical and biochemical analyses demonstrated that the endogenous mouse tau is transiently expressed in neonatal brains, that exogenous human tau expressed corresponding to such tau expression profile can distribute into the axon, and that the constitutive expression of tau into adulthood (e.g., human tau in transgenic mice) results in abnormal somatodendritic localization. Thus, the expression profile of tau is tightly associated with the localization of tau, and the ectopic expression of tau in matured neurons may be involved in the pathogenesis of tauopathy.

    DOI: 10.1523/JNEUROSCI.2845-18.2019

    PubMed

    researchmap

  • 【細胞内の相分離 タンパク質や核酸分子を整理し、反応の場を作り、生命を駆動する】ALS病態における液-液相分離と非膜性構造の異常 Reviewed

    小池 佑佳, 石原 智彦, 小野寺 理

    実験医学   37 ( 9 )   1416 - 1420   2019.6

     More details

    Language:Japanese   Publisher:(株)羊土社  

    TDP-43やFUSに代表される、筋萎縮性側索硬化症(ALS)関連タンパク質の多くは、RNA結合タンパク質であり、複数の生体高分子と凝集し、非膜性の集合体を形成する。この現象は液-液相分離(LLPS)とよばれる。LLPSと類似の挙動を呈する非膜性の細胞構造の一つであるGEM小体は、スプライソソーム成熟に寄与する。われわれは、TDP-43発現抑制細胞とALS患者由来組織において、GEM小体数減少を示した。このことは、ALS関連タンパク質の機能喪失により、スプライソソーム機能不全を介したスプライシング破綻が生じることを示す。(著者抄録)

    researchmap

  • Angiogenesis in the ischemic core: A potential treatment target? Reviewed International journal

    Masato Kanazawa, Tetsuya Takahashi, Masanori Ishikawa, Osamu Onodera, Takayoshi Shimohata, Gregory J Del Zoppo

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism   39 ( 5 )   753 - 769   2019.5

     More details

    Language:English  

    The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments.

    DOI: 10.1177/0271678X19834158

    PubMed

    researchmap

  • Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases. Reviewed International journal

    Hidetomo Tanaka, Shinobu Kawakatsu, Yasuko Toyoshima, Takeshi Miura, Naomi Mezaki, Atsushi Mano, Kazuhiro Sanpei, Ryota Kobayashi, Hiroshi Hayashi, Koichi Otani, Takeshi Ikeuchi, Osamu Onodera, Akiyoshi Kakita, Hitoshi Takahashi

    Neuropathology : official journal of the Japanese Society of Neuropathology   39 ( 2 )   111 - 119   2019.4

     More details

    Language:English  

    Globular glial tauopathies (GGTs) are four-repeat tauopathies characterized by the presence of two types of tau-positive globular glial inclusions (GGIs): globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). GGTs are classified into three different neuropathological subtypes: Types I, II and III. We report two patients with GGTs - a 76-year-old woman and a 70-year-old man - in whom the disease duration was 5 and 6 years, respectively. Both patients exhibited upper and lower motor neuron signs and involuntary movements, and the latter also had dementia with frontotemporal cerebral atrophy evident on magnetic resonance imaging. Neuropathologically, in both cases, the precentral gyrus was most severely affected, and at the gray-white matter junction there was almost complete loss of Betz cells and occurrence of GOIs and coiled bodies with numerous neuropil threads. Both patients also showed neuronal loss and GGIs (mostly GOIs) in many other central nervous system regions, including the basal ganglia. Apart from the degree of regional severity, the distribution pattern was essentially the same in both cases. However, GAIs were not conspicuous in any of the affected regions. Based on the morphology and distribution pattern of the GGIs, we diagnosed the present two patients as having GGT Type II. Electron microscopic and biochemical findings in the former were consistent with the diagnosis. Type II cases are reported to be characterized by pyramidal features reflecting predominant motor cortex and corticospinal tract degeneration. The present observations suggest that a variety of neurological features, including dementia, can occur in GGT Type II reflecting widespread degeneration beyond the motor neuron system.

    DOI: 10.1111/neup.12532

    PubMed

    researchmap

  • Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy. Reviewed International journal

    Koji Kato, Ryo Maemura, Manabu Wakamatsu, Ayako Yamamori, Motoharu Hamada, Shinsuke Kataoka, Atsushi Narita, Shunsuke Miwata, Yuko Sekiya, Nozomu Kawashima, Kyogo Suzuki, Kotaro Narita, Sayoko Doisaki, Hideki Muramatsu, Hirotoshi Sakaguchi, Kimikazu Matsumoto, Yuka Koike, Osamu Onodera, Makiko Kaga, Nobuyuki Shimozawa, Nao Yoshida

    Molecular genetics and metabolism reports   18   1 - 6   2019.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Objective: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution. Patients: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1). Results: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement. Conclusion: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.

    DOI: 10.1016/j.ymgmr.2018.11.001

    PubMed

    researchmap

  • Low serum 25-hydroxyvitamin D increases cognitive impairment in elderly people. Reviewed

    Mayumi Sakuma, Kaori Kitamura, Naoto Endo, Takeshi Ikeuchi, Akio Yokoseki, Osamu Onodera, Takeo Oinuma, Takeshi Momotsu, Kenji Sato, Kazutoshi Nakamura, Ichiei Narita

    Journal of bone and mineral metabolism   37 ( 2 )   368 - 375   2019.3

     More details

    Language:English  

    It has been reported that many elderly people have low serum levels of 25-hydroxyvitamin D [25(OH)D] and that serum 25(OH)D levels may have a relationship with cognitive function. The aim of this study was to examine the relationship between serum 25(OH)D levels and cognitive function in a Japanese population. This cross-sectional study was performed as a part of the Project in Sado for Total Health (PROST). The PROST study evaluated cognitive state and serum vitamin D level from June 2011 to November 2013 for 740 patients (431 men and 309 women). The Mini-Mental State Examination-Japanese version (MMSE-J) and serum 25(OH)D level measurements were used as assessment tools. Cognitive impairment was defined using MMSE-J ≤ 23 as a cutoff. Multiple logistic regression analyses were performed to calculate the odds ratios (ORs) for low MMSE-J scores. The average subject age was 68.1 years, the average MMSE- J score was 25.9, and the average 25(OH)D level was 24.6 ng/mL. Significant ORs for cognitive impairment were observed for both high age and low serum 25(OH)D. The adjusted OR for the lowest versus highest serum 25(OH)D quartiles was 2.70 (95% confidence interval 1.38-5.28, P = 0.0110). Low serum 25(OH)D levels were independently associated with a higher prevalence of cognitive impairment.

    DOI: 10.1007/s00774-018-0934-z

    PubMed

    researchmap

  • 【神経疾患とトレース・メタル-知っていますか?】鉄 Friedreich失調症と鉄代謝 Reviewed

    坪口 晋太朗, 石原 智彦, 小野寺 理

    Clinical Neuroscience   37 ( 3 )   308 - 310   2019.3

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • Neuropathologic characteristics of patients with progressive suprenuclear palsy who died within four years after the disease onset

    Lu Zhang, Yasuko Toyoshima, Akari Takeshima, Hiroshi Shimizu, Itsuro Tomita, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    BRAIN PATHOLOGY   29   77 - 77   2019.2

     More details

    Language:English   Publisher:WILEY  

    Web of Science

    researchmap

  • Radiological, immunological, and pathological analysis of ependymal cells in neuromyelitis spectrum disorders

    Fumihiro Yanagimura, Etsuji Saji, Takahiro Wakasugi, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Osamu Onodera, Izumi Kawachi

    BRAIN PATHOLOGY   29   134 - 134   2019.2

     More details

    Language:English   Publisher:WILEY  

    Web of Science

    researchmap

  • Is the population of Sado Island genetically close to the population of western Japan? Reviewed International journal

    Kazuharu Misawa, Hiroshi Watanabe, Akio Yokoseki, Minako Wakasugi, Osamu Onodera, Ichiei Narita, Takeshi Momotsu, Kenji Sato, Naoto Endo

    Human genome variation   6   26 - 26   2019

     More details

    Language:English  

    To explore the effect of aging, a cohort study is being performed on Sado Island, which is located in the Sea of Japan. Sado Island is close to the eastern coast of Japan, yet its population speaks the western Japanese dialect. Consequently, the genetic background of the population of Sado Island is of interest. Based on Nei's genetic distance, we compared the allele frequencies of people from Sado Island to those of people from Nagahama and Miyagi, which are located in the western and northeastern parts of Honshu, respectively. The results showed that the populations of Miyagi and Nagahama are genetically closer to each other than to the population of Sado Island. Because the Sado and Honshu Islands are isolated by a channel, it is possible that genetic drift occurred within Sado Island, which would explain the uniqueness of the people of this region.

    DOI: 10.1038/s41439-019-0058-6

    PubMed

    researchmap

  • A patient clinically diagnosed as multiple system atrophy harboring LRRK2 p.G2019S

    Shoichiro Ando, Takuya Konno, Tomohiko Ishihara, Hideki Hayashi, Natsumi Saito, Kenya Nishioka, Nobutaka Hattori, Zbigniew K. Wszolek, Osamu Onodera

    Clinical Parkinsonism & Related Disorders   1   100 - 101   2019

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.prdoa.2019.11.002

    researchmap

  • Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. Reviewed International journal

    Naomi Mezaki, Takeshi Miura, Kotaro Ogaki, Makoto Eriguchi, Yuri Mizuno, Kenichi Komatsu, Hiroki Yamazaki, Natsuki Suetsugi, Sumihiro Kawajiri, Ryo Yamasaki, Takanobu Ishiguro, Takuya Konno, Hiroaki Nozaki, Kensaku Kasuga, Yasuyuki Okuma, Jun-Ichi Kira, Hideo Hara, Osamu Onodera, Takeshi Ikeuchi

    Neurology. Genetics   4 ( 6 )   e292   2018.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Objective: To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1). Methods: Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed. Results: We identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region. Conclusions: We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.

    DOI: 10.1212/NXG.0000000000000292

    PubMed

    researchmap

  • CADM1 is a diagnostic marker in early-stage mycosis fungoides: Multicenter study of 58 cases Reviewed International journal

    Akihiko Yuki, Satoru Shinkuma, Ryota Hayashi, Hiroki Fujikawa, Taisuke Kato, Erina Homma, Yohei Hamade, Osamu Onodera, Masao Matsuoka, Hiroshi Shimizu, Hiroaki Iwata, Riichiro Abe

    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY   79 ( 6 )   1039 - 1046   2018.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MOSBY-ELSEVIER  

    Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Early-stage MF patches or plaques often resemble inflammatory skin disorders (ISDs), including psoriasis and atopic dermatitis. Cell adhesion molecule 1 gene (CADM1), which was initially identified as a tumor suppressor gene in human non-small cell lung cancer, has been reported as a diagnostic marker for adult T-cell leukemia/lymphoma.Objective: We investigated CADM1 expression in MF neoplastic cells, especially during early stages, and evaluated its usefulness as a diagnostic marker for MF.Methods: We conducted a retrospective study by using immunohistochemical staining and confirmed the expression of CADM1 in MF. In addition, we compared CADM1 messenger RNA expression in microdissected MF samples and ISD samples.Results: In the overall study period, 55 of 58 MF samples (94.8%) stained positive for CADM1. None of the 50 ISD samples showed positive reactivity (P < .0001). We found CADM1 messenger RNA expression in the intradermal lymphocytes of patients with MF but not in those of patients with an ISD.Limitations: We did not conduct a validation study for MF cases in other institutions.Conclusions: CADM1-positive cells can be identified in early stages with fewer infiltrating cells and may be useful as a diagnostic marker for early-stage MF.

    DOI: 10.1016/j.jaad.2018.06.025

    Web of Science

    PubMed

    researchmap

  • 本邦におけるCADASILの現状 Reviewed

    新堂 晃大, 田部井 賢一, 谷口 彰, 小野寺 理, 猪原 匡史, 水野 敏樹, 冨本 秀和

    臨床神経学   58 ( Suppl. )   S310 - S310   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 進行性核上性麻痺における臨床型別臨床経過の検討 多施設共同前向きコホート研究

    饗場 郁子, 池内 健, 瀧川 洋史, 徳田 隆彦, 下畑 享良, 森田 光哉, 村山 繁雄, 小野寺 理, 長谷川 一子, 古和 久典, 花島 律子, 中島 健二, JALPACコンソーシアム

    臨床神経学   58 ( Suppl. )   S211 - S211   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PSP Rating Scaleによる進行性核上性麻痺の経時的変化に関する検討

    瀧川 洋史, 池内 健, 饗場 郁子, 森田 光哉, 小野寺 理, 下畑 享良, 徳田 隆彦, 村山 繁雄, 長谷川 一子, 古和 久典, 花島 律子, 中島 健二, JALPACコンソーシアム

    臨床神経学   58 ( Suppl. )   S261 - S261   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Clinicopathologic Features of Two Patients With Sporadic Amyotrophic Lateral Sclerosis Who Maintained Communication Ability for Over 30 Years. Reviewed International journal

    Junko Ito, Tetsuro Shimada, Mari Tada, Hiroshi Shimizu, Masatoshi Wakabayashi, Akio Yokoseki, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   77 ( 11 )   981 - 986   2018.11

     More details

    Language:English  

    We report the clinicopathologic features of 2 unrelated patients with sporadic amyotrophic lateral sclerosis (SALS) supported by tracheostomy and invasive ventilation (TIV) who were able to maintain communication ability for more than 30 years after disease onset. In both cases, the age at onset was younger than the mean, initially the progression of muscle weakness was consistent with that in the majority of SALS patients, and TIV became necessary several years after disease onset. Thereafter, however, their neurologic deterioration slowed and the patients were able to operate computers by facial movements for several decades. At autopsy, neuronal loss appeared to be confined to the motor neuron system. Furthermore, while Betz cells and lower motor neurons in the spinal anterior horns and hypoglossal nucleus were severely depleted, other pyramidal neurons in the motor cortex, and lower motor neurons in the other brainstem motor nuclei were retained. Neuronal and glial cytoplasmic inclusions immunoreactive for phosphorylated 43-kDa TAR DNA-binding protein (TDP-43) were evident in the CNS, but in extremely small numbers. The present patients may represent a distinct subgroup of patients with SALS who are able to maintain communication ability for an extremely long period, accompanied by very mild TDP-43 pathology.

    DOI: 10.1093/jnen/nly082

    PubMed

    researchmap

  • Identification and functional characterization of novel mutations including frameshift mutation in exon 4 of CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. Reviewed International journal

    Takeshi Miura, Naomi Mezaki, Takuya Konno, Akio Iwasaki, Naoyuki Hara, Masatomo Miura, Michitaka Funayama, Yuki Unai, Yuichi Tashiro, Kenji Okita, Takeshi Kihara, Nobuo Ito, Yoichi Kanatsuka, David T Jones, Norikazu Hara, Takanobu Ishiguro, Takayoshi Tokutake, Kensaku Kasuga, Hiroaki Nozaki, Dennis W Dickson, Osamu Onodera, Zbigniew K Wszolek, Takeshi Ikeuchi

    Journal of neurology   265 ( 10 )   2415 - 2424   2018.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by mutations in CSF1R. Pathogenic mutations in exons 12-22 including coding sequence of the tyrosine kinase domain (TKD) of CSF1R were previously identified. We aimed to identify CSF1R mutations in patients who were clinically suspected of having ALSP and to determine the pathogenicity of novel CSF1R variants. METHODS: Sixty-one patients who fulfilled the diagnostic criteria of ALSP were included in this study. Genetic analysis of CSF1R was performed for all the coding exons. The haploinsufficiency of CSF1R was examined for frameshift mutations by RT-PCR. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing CSF1R mutants. RESULTS: We identified ten variants in CSF1R including two novel frameshift, five novel missense, and two known missense mutations as well as one known missense variant. Eight mutations were located in TKD. One frameshift mutation (p.Pro104LeufsTer8) and one missense variant (p.His362Arg) were located in the extracellular domain. RT-PCR analysis revealed that the frameshift mutation of p.Pro104LeufsTer8 caused nonsense-mediated mRNA decay. Functional assay revealed that none of the mutations within TKD showed autophosphorylation of CSF1R. The p.His362Arg variant located in the extracellular domain showed comparable autophosphorylation of CSF1R to the wild type, suggesting that this variant is not likely pathogenic. CONCLUSIONS: The detection of the CSF1R mutation outside of the region-encoding TKD may extend the genetic spectrum of ALSP with CSF1R mutations. Mutational analysis of all the coding exons of CSF1R should be considered for patients clinically suspected of having ALSP.

    DOI: 10.1007/s00415-018-9017-2

    PubMed

    researchmap

  • ショウジョウバエモデルによるC9-ALS/FTDの病態解明

    上山 盛夫, 石黒 太郎, Gendron Tania F, 今野 卓哉, 小山 哲秀, 望月 秀樹, 和田 圭司, 石川 欣也, 小野寺 理, 永井 義隆

    Dementia Japan   32 ( 3 )   435 - 435   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Histopathologic features of an autopsied patient with cerebral small vessel disease and a heterozygous HTRA1 mutation. Reviewed International journal

    Junko Ito, Hiroaki Nozaki, Yasuko Toyoshima, Takashi Abe, Aki Sato, Hideki Hashidate, Shuichi Igarashi, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   2018.5

     More details

    Language:English  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary cerebral small vessel disease (CSVD) caused by homozygous or compound heterozygous mutations of the high temperature requirement A serine peptidase 1 gene (HTRA1). Affected patients suffer from cognitive impairment, recurrent strokes, lumbago and alopecia. Recently, clinical studies have indicated that some patients with heterozygous mutations in HTRA1 may also suffer CSVD. Here, we report the histopathologic features of an autopsied 55-year-old male patient who had shown cognitive impairment and multiple cerebral infarcts, and was found to have a heterozygous missense mutation (p.R302Q) in the HTRA1 gene. Histologically, small vessels in the brain and spinal cord showed intimal proliferation, splitting of the internal elastic lamina, and degeneration of smooth muscle cells in the tunica media. Thus, although less severe, the features were quite similar to those of patients with CARASIL, indicating that patients with heterozygous mutations develop CSVD through underlying pathomechanisms similar to those of CARASIL.

    DOI: 10.1111/neup.12473

    PubMed

    researchmap

  • Predictors of cognitive impairment in multiple system atrophy. Reviewed International journal

    Masahiro Hatakeyama, Tomoe Sato, Tetsuya Takahashi, Masato Kanazawa, Osamu Onodera, Masatoyo Nishizawa, Takayoshi Shimohata

    Journal of the neurological sciences   388   128 - 132   2018.5

     More details

    Language:English  

    OBJECTIVE: To determine predictors of cognitive impairment and frontal dysfunction in patients with multiple system atrophy (MSA). METHODS: We recruited 59 patients with MSA and determined the predictors of a decline in the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores. RESULTS: The MMSE scores negatively correlated with disease duration, Unified MSA Rating Scale (UMSARS) part 1 and 4 scores, and residual urine volume, and positively correlated with the coefficient of variation of electrocardiographic RR intervals. The FAB scores negatively correlated with the UMSARS part 2 score, periventricular hyperintensity grade, and deep white matter hyperintense signal grade. A significant predictor of rapidly progressive cognitive impairment was a high residual urine volume. CONCLUSIONS: Impairment of global cognitive function correlates with the long-term disease duration, global disability due to the disease, and autonomic dysfunction, whereas frontal dysfunction correlates with motor function and degeneration of cerebral white matter.

    DOI: 10.1016/j.jns.2018.03.017

    PubMed

    researchmap

  • Loss of Motor Neurons Innervating Cervical Muscles in Patients With Multiple System Atrophy and Dropped Head. Reviewed International journal

    Rie Saito, Mari Tada, Yasuko Toyoshima, Masatoyo Nishizawa, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   77 ( 4 )   317 - 324   2018.4

     More details

    Language:English  

    We investigated whether loss of motor neurons innervating the neck muscles contributes to dropped head (DH) in multiple system atrophy (MSA). From 75 patients with autopsy-proven MSA, we retrieved 3 who had DH (MSA-DH), and examined the 4th cervical cord segments. Neurons of the medial and lateral nuclear groups (MNG and LNG) innervate the neck and shoulder muscles, respectively. We measured the area of individual neurons in the MNG and LNG, and created an area-frequency histogram. Neurons were classified as large or small based on their area, and their total numbers in the MNG and LNG were counted. In the MNG, the numbers of both total neurons and large neurons were significantly lower in MSA patients than in the controls (214.2 ± 91.4 vs 521.3 ± 74.8, p = 0.0030, and 26.2 ± 9.1 vs 88.0 ± 34.6, p = 0.020, respectively), and were significantly lower in MSA-DH than in MSA-nonDH (139.7 ± 7.6 vs 288.7 ± 74.6, p = 0.048, and 18.0 ± 4.1 vs 34.3 ± 4.1, p = 0.016, respectively). There were no differences in the LNG neuron counts between the MSA-DH and MSA-nonDH groups. Loss of cervical motor neurons may be responsible for DH in MSA.

    DOI: 10.1093/jnen/nly007

    PubMed

    researchmap

  • Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy. Reviewed International journal

    Hiroyuki Ishiura, Koichiro Doi, Jun Mitsui, Jun Yoshimura, Miho Kawabe Matsukawa, Asao Fujiyama, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Yutaka Suzuki, Sumio Sugano, Wei Qu, Kazuki Ichikawa, Hideaki Yurino, Koichiro Higasa, Shota Shibata, Aki Mitsue, Masaki Tanaka, Yaeko Ichikawa, Yuji Takahashi, Hidetoshi Date, Takashi Matsukawa, Junko Kanda, Fumiko Kusunoki Nakamoto, Mana Higashihara, Koji Abe, Ryoko Koike, Mutsuo Sasagawa, Yasuko Kuroha, Naoya Hasegawa, Norio Kanesawa, Takayuki Kondo, Takefumi Hitomi, Masayoshi Tada, Hiroki Takano, Yutaka Saito, Kazuhiro Sanpei, Osamu Onodera, Masatoyo Nishizawa, Masayuki Nakamura, Takeshi Yasuda, Yoshio Sakiyama, Mieko Otsuka, Akira Ueki, Ken-Ichi Kaida, Jun Shimizu, Ritsuko Hanajima, Toshihiro Hayashi, Yasuo Terao, Satomi Inomata-Terada, Masashi Hamada, Yuichiro Shirota, Akatsuki Kubota, Yoshikazu Ugawa, Kishin Koh, Yoshihisa Takiyama, Natsumi Ohsawa-Yoshida, Shoichi Ishiura, Ryo Yamasaki, Akira Tamaoka, Hiroshi Akiyama, Taisuke Otsuki, Akira Sano, Akio Ikeda, Jun Goto, Shinichi Morishita, Shoji Tsuji

    Nature genetics   50 ( 4 )   581 - 590   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.

    DOI: 10.1038/s41588-018-0067-2

    PubMed

    researchmap

  • Frequency and characteristics of the TBK1 gene variants in Japanese patients with sporadic amyotrophic lateral sclerosis. Reviewed International journal

    Genki Tohnai, Ryoichi Nakamura, Jun Sone, Masahiro Nakatochi, Daichi Yokoi, Masahisa Katsuno, Hazuki Watanabe, Hirohisa Watanabe, Mizuki Ito, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Masashi Aoki, Nobutaka Hattori, Osamu Onodera, Hiroya Naruse, Jun Mitsui, Yuji Takahashi, Jun Goto, Hiroyuki Ishiura, Shinichi Morishita, Jun Yoshimura, Koichiro Doi, Shoji Tsuji, Kenji Nakashima, Ryuji Kaji, Naoki Atsuta, Gen Sobue

    Neurobiology of aging   64   158.e15-158.e19 - 158.e19   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67-62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.

    DOI: 10.1016/j.neurobiolaging.2017.12.005

    PubMed

    researchmap

  • Case Report: A patient with spinocerebellar ataxia type 31 and sporadic Creutzfeldt-Jakob disease. Reviewed International journal

    Natsumi Saito, Tomohiko Ishihara, Kensaku Kasuga, Mana Nishida, Takanobu Ishiguro, Hiroaki Nozaki, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa

    Prion   12 ( 2 )   147 - 149   2018.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    We report a Japanese patient with spinocerebellar ataxia type 31 (SCA31) and sporadic Creutzfeldt-Jakob disease (sCJD). A 52-year-old man developed progressive cognitive impairment after the appearance of cerebellar symptoms. Brain MR diffusion-weighted imaging (DWI) demonstrated a slowly expanding hyperintense lesion in the cerebral cortex. The patient was finally diagnosed as having both SCA31 and sCJD by identification of genetic mutations and by real-time quaking-induced conversion (RT-QUIC) analysis of the cerebrospinal fluid (CSF), respectively. Here, we report the clinical details of this rare combined case, with particular reference to the association between prion protein and the early onset of SCA31.

    DOI: 10.1080/19336896.2018.1436926

    PubMed

    researchmap

  • Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation Reviewed

    T. Konno, K. Yoshida, I. Mizuta, T. Mizuno, T. Kawarai, M. Tada, H. Nozaki, S. I. Ikeda, O. Onodera, Z. K. Wszolek, T. Ikeuchi

    European Journal of Neurology   25 ( 1 )   142 - 147   2018.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blackwell Publishing Ltd  

    Background and purpose: To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation. Methods: We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide ‘probable’ and ‘possible’ designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations. Results: Among the CSF1R mutation-positive cases, 50 cases (60%) were diagnosed as ‘probable’ and 32 (39%) were diagnosed as ‘possible,’ leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled ‘probable’ or ‘possible’ to the total number of cases. With regard to specificity, 22 cases (42%) with mutation-negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria. Conclusions: These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.

    DOI: 10.1111/ene.13464

    Scopus

    PubMed

    researchmap

  • Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation Reviewed

    T. Konno, K. Yoshida, I. Mizuta, T. Mizuno, T. Kawarai, M. Tada, H. Nozaki, S. I. Ikeda, O. Onodera, Z. K. Wszolek, T. Ikeuchi

    European Journal of Neurology   25 ( 1 )   142 - 147   2018.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blackwell Publishing Ltd  

    Background and purpose: To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation. Methods: We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide ‘probable’ and ‘possible’ designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations. Results: Among the CSF1R mutation-positive cases, 50 cases (60%) were diagnosed as ‘probable’ and 32 (39%) were diagnosed as ‘possible,’ leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled ‘probable’ or ‘possible’ to the total number of cases. With regard to specificity, 22 cases (42%) with mutation-negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria. Conclusions: These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.

    DOI: 10.1111/ene.13464

    Scopus

    PubMed

    researchmap

  • Operation of a P300-based brain-computer interface in patients with Duchenne muscular dystrophy Reviewed International journal

    Kota Utsumi, Kouji Takano, Yoji Okahara, Tetsuo Komori, Osamu Onodera, Kenji Kansaku

    SCIENTIFIC REPORTS   8 ( 1 )   1753 - 1753   2018.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    A brain-computer interface (BCI) or brain-machine interface is a technology that enables the control of a computer and other external devices using signals from the brain. This technology has been tested in paralysed patients, such as those with cervical spinal cord injuries or amyotrophic lateral sclerosis, but it has not been tested systematically in Duchenne muscular dystrophy (DMD), which is a severe type of muscular dystrophy due to the loss of dystrophin and is often accompanied by progressive muscle weakness and wasting. Here, we investigated the efficacy of a P300-based BCI for patients with DMD. Eight bedridden patients with DMD and eight age-and gender-matched able-bodied controls were instructed to input hiragana characters. We used a region-based, two-step P300-based BCI with green/blue flicker stimuli. EEG data were recorded, and a linear discriminant analysis distinguished the target from other non-targets. The mean online accuracy of inputted characters (accuracy for the two-step procedure) was 71.6% for patients with DMD and 80.6% for controls, with no significant difference between the patients and controls. The P300-based BCI was operated successfully by individuals with DMD in an advanced stage and these findings suggest that this technology may be beneficial for patients with this disease.

    DOI: 10.1038/s41598-018-20125-6

    Web of Science

    PubMed

    researchmap

  • CARASIL families from India with 3 novel null mutations in the HTRA1 gene. Reviewed International journal

    Veeramani Preethish-Kumar, Hiroaki Nozaki, Sarbesh Tiwari, Seena Vengalil, Maya Bhat, Chandrajit Prasad, Osamu Onodera, Masahiro Uemura, Seshagiri Doniparthi, Jitender Saini, Saraswati Nashi, Kiran Polavarapu, Atchayaram Nalini

    Neurology   89 ( 23 )   2392 - 2394   2017.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1212/WNL.0000000000004710

    PubMed

    researchmap

  • Clinical/scientific notes Reviewed

    Veeramani Preethish-Kumar, Hiroaki Nozaki, Sarbesh Tiwari, Seena Vengalil, Maya Bhat, Chandrajit Prasad, Osamu Onodera, Masahiro Uemura, Seshagiri Doniparthi, Jitender Saini, Saraswati Nashi, Kiran Polavarapu, Atchayaram Nalini

    Neurology   89 ( 23 )   2392 - 2394   2017.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Lippincott Williams and Wilkins  

    DOI: 10.1212/WNL.0000000000004710

    Scopus

    PubMed

    researchmap

  • The SMN gene copy number states in Japanese ALS patients

    Ishihara T, Toyoda S, Koyama A, Tada M, Atsuta N, Nakamura R, Tohnai G, Sone J, Izumi Y, Kaji R, Morita M, Taniguchi A, Kakita A, Sobue G, Nishizawa M, Onodera O

    JOURNAL OF THE NEUROLOGICAL SCIENCES   381   211-211   2017.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.604

    researchmap

  • New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan. Reviewed International journal

    Ikuko Mizuta, Akiko Watanabe-Hosomi, Takashi Koizumi, Mao Mukai, Ai Hamano, Yasuhiro Tomii, Masaki Kondo, Masanori Nakagawa, Hidekazu Tomimoto, Teruyuki Hirano, Makoto Uchino, Osamu Onodera, Toshiki Mizuno

    Journal of the neurological sciences   381   62 - 67   2017.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    PURPOSE: Definite diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy (CADASIL) is mostly done by identification of NOTCH3 mutations. We aimed to develop criteria for selecting patients suspected for CADASIL to undergo genetic testing. SUBJECTS AND METHODS: All subjects were Japanese. We recruited CADASIL patients genetically diagnosed up until 2011 (n=37, Group 1) or after 2011 (n=65, Group 2), 67 young stroke patients (≤55 years old), and 53 NOTCH3-negative CADASIL-like patients. The members of Japanese research committee for hereditary cerebral small vessel disease discussed and generated the new criteria to maximize positive rate in Group 1 CADASIL patients, followed by validation of sensitivity and specificity. RESULTS: In Group 1 CADASIL patients, the ages at onset excluding migraine were distributed widely (37-74 years old) and bimodal (<55 and >55 years old). Frequencies of an autosomal dominant family history and vascular risk factor(s) were 73 and 65%, respectively. From these findings, the panel considered appropriate cut-off values and weighting for each item. In CADASIL Group 1 versus young stroke controls, the sensitivity and specificity of the new criteria were 97.3% and 80.6%, respectively. However, in CADASIL Group 2 versus NOTCH3-negative controls, the sensitivity and specificity were 96.9% and 7.5%, respectively. Forty mutations of NOTCH3 distributed in exons 2-8, 11, 14, 18, 19, and 21 were identified in this study. Ten mutations were unreported ones. CONCLUSION: We propose the new criteria of high sensitivity, which will help physicians to assess the need for genetic testing.

    DOI: 10.1016/j.jns.2017.08.009

    PubMed

    researchmap

  • Apparent diffusion coefficient reduction might be a predictor of poor outcome in patients with posterior reversible encephalopathy syndrome. Reviewed International journal

    Itaru Ninomiya, Masato Kanazawa, Yasuhisa Akaiwa, Takayoshi Shimohata, Kouichirou Okamoto, Osamu Onodera, Masatoyo Nishizawa

    Journal of the neurological sciences   381   1 - 3   2017.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    It is thought that posterior reversible encephalopathy syndrome (PRES) is both clinically and radiologically reversible. However, its reversible nature has been challenged based on reports of permanent neurological impairments. The factors that predict the development of irreversible neurological impairment are still unclear. In the present study, we investigated clinical manifestations, laboratory findings, and neuroradiological images to identify predictors of functional outcomes in PRES. We investigated 23 PRES patients. Apparent diffusion coefficient (ADC) reduction was observed in 4 patients in the poor outcome group, whereas no patients presented ADC reduction in the favourable outcome group (p<0.01). Further studies are warranted to evaluate the association between ADC reduction and functional outcome after PRES.

    DOI: 10.1016/j.jns.2017.08.002

    PubMed

    researchmap

  • Association between dialysis treatment and cognitive decline: A study from the Project in Sado for Total Health (PROST), Japan Reviewed

    Yumi Watanabe, Kaori Kitamura, Kazutoshi Nakamura, Kazuhiro Sanpei, Minako Wakasugi, Akio Yokoseki, Keiko Kabasawa, Osamu Onodera, Takeshi Ikeuchi, Ryozo Kuwano, Takeshi Momotsu, Ichici Narita, Naoto Endo

    GERIATRICS & GERONTOLOGY INTERNATIONAL   17 ( 10 )   1584 - 1587   2017.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Aim: Evidence for the association between dialysis treatment and cognitive decline is limited. The present study aimed to determine whether dialysis treatment is associated with cognitive decline in adult outpatients of a general hospital in Japan.Methods: This was a cross-sectional substudy of the Project in Sado for Total Etealth (PROST). Total Etealth PROST targeted adult outpatients of a general hospital in Sado City, Niigata, Japan. Among 753 patients (mean age 68.1 11.6 years) analyzed, 66 received dialysis. Cognitive state was evaluated using the Mini-Mental State Examination, and those with a Mini-Mental State Examination score <24 were considered "cognitively declined." The prevalence of cognitive decline was compared by odds ratios calculated with multiple logistic regression analysis. Variables included in the analyses were dialysis, age, sex and self-reported histories of hypertension, diabetes, stroke and ischemic heart disease.Results: Of the 66 dialysis patients, 24 (36.4%) showed cognitive decline, whereas 172 (25.0%) of 687 non-dialysis patients showed cognitive decline. The age and sex-adjusted odds ratio for cognitive decline in dialysis patients was 2.57 (95% confidence interval 1.43-4.61), relative to non-dialysis patients. The odds ratio remained significant (odds ratio 2.69, 95% confidence interval 1.49-4.88) even after adjusting for all covariates.Conclusion: The prevalence of cognitive decline was high in dialysis patients relative to non-dialysis patients among outpatients of a general hospital in Japan..

    DOI: 10.1111/ggi.12937

    Web of Science

    PubMed

    researchmap

  • Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson's disease Reviewed

    Kahori Shiba-Fukushima, Kei-Ichi Ishikawa, Tsuyoshi Inoshita, Nana Izawa, Masashi Takanashi, Shigeto Sato, Osamu Onodera, Wado Akamatsu, Hideyuki Okano, Yuzuru Imai, Nobutaka Hattori

    HUMAN MOLECULAR GENETICS   26 ( 16 )   3172 - 3185   2017.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    The ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase Parkin, two gene products associated with young-onset Parkinson's disease (PD), participate in mitochondrial quality control. The phosphorylation of mitochondrial polyUb by PINK1, which is activated in a mitochondrial membrane potential (Delta Psi m)-dependent manner, facilitates the mitochondrial translocation and concomitant enzymatic activation of Parkin, leading to the clearance of phospho-polyUb-tagged mitochondria via mitophagy. Thus, Ub phosphorylation is a key event in PINK1-Parkin-mediated mitophagy. Here, we examined the role of phospho-Ub signaling in the pathogenesis of PD using fly PD models, human brain tissue and dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) containing Parkin or PINK1 mutations, as well as normal controls. We report that phospho-Ub signaling is highly conserved between humans and Drosophila, and that phospho-Ub signaling and the relocation of axonal mitochondria upon Delta Psi m reduction are indeed compromised in human dopaminergic neurons containing Parkin or PINK1 mutations. Moreover, phospho-Ub signaling is prominent in tyrosine hydroxylase-positive neurons compared with tyrosine hydroxylase-negative neurons, suggesting that PINK1-Parkin signaling is more required for dopaminergic neurons. These results shed light on the particular vulnerability of dopaminergic neurons to mitochondrial stress.

    DOI: 10.1093/hmg/ddx201

    Web of Science

    PubMed

    researchmap

  • [Overview of Hereditary Spinocerebellar Ataxias in Japan]. Reviewed

    Masayoshi Tada, Akio Yokoseki, Osamu Onodera

    Brain and nerve = Shinkei kenkyu no shinpo   69 ( 8 )   879 - 890   2017.8

     More details

    Language:Japanese  

    Hereditary spinocerebellar degenerations (SCD) are a group of neurodegenerative disorders characterized by slowly progressive ataxia associated with non-cerebellar neurological signs and symptoms. In the Japanese population, dominantly inherited SCDs are much more common than recessively inherited or X-linked SCDs. The most common dominantly inherited SCD in Japan, as well as in many other countries, is Machado-Joseph disease, also known as spinocerebellar ataxia type 3 (MJD/SCA3). MJD/SCA3 is frequently accompanied by non-cerebellar symptoms, including progressive external ophthalmoplegia, pyramidal signs, dystonia, rigidity, dysarthria, and distal muscle atrophies. SCA6 and SCA31 represent a pure cerebellar subtype of SCD, occasionally accompanied by non-cerebellar signs. Detailed medical history and neurological examination are important for clinicians to diagnose hereditary SCDs, although genetic testing can help confirm the diagnosis. Despite increasing understanding of the molecular mechanisms underlying these fatal diseases, preventive therapies are currently lacking.

    DOI: 10.11477/mf.1416200839

    PubMed

    researchmap

  • The Clinical Features, Risk Factors, and Surgical Treatment of Cervicogenic Headache in Patients With Cervical Spine Disorders Requiring Surgery Reviewed

    Keiko Shimohata, Kazuhiro Hasegawa, Osamu Onodera, Masatoyo Nishizawa, Takayoshi Shimohata

    HEADACHE   57 ( 7 )   1109 - 1117   2017.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Objective.-To clarify the clinical features and risk factors of cervicogenic headache (CEH; as diagnosed according to the International Classification of Headache Disorders-Third Edition beta) in patients with cervical spine disorders requiring surgery.
    Background.-CEH is caused by cervical spine disorders. The pathogenic mechanism of CEH is hypothesized to involve a convergence of the upper cervical afferents from the C1, C2, and C3 spinal nerves and the trigeminal afferents in the trigeminocervical nucleus of the upper cervical cord. According to this hypothesis, functional convergence of the upper cervical and trigeminal sensory pathways allows the bidirectional (afferent and efferent) referral of pain to the occipital, frontal, temporal, and/or orbital regions. Previous prospective studies have reported an 86-88% prevalence of headache in patients with cervical myelopathy or radiculopathy requiring anterior cervical surgery; however, these studies did not diagnose headache according to the International Classification of Headache Disorders criteria. Therefore, a better understanding of the prevalence rate, clinical features, risk factors, and treatment responsiveness of CEH in patients with cervical spine disorders requiring surgery is necessary.
    Methods.-We performed a single hospital-based prospective cross-sectional study and enrolled 70 consecutive patients with cervical spine disorders such as cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, cervical spondylotic radiculopathy, and cervical spondylotic myeloradiculopathy who had been scheduled to undergo anterior cervical fusion or dorsal cervical laminoplasty between June 2014 and December 2015. Headache was diagnosed preoperatively according to the International Classification of Headache Disorders-Third Edition beta. The Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, Neck Disability Index, and a 0-100 mm visual analog scale (VAS) were used to evaluate clinical features, and scores were compared between baseline (ie, preoperatively) and 3, 6, and 12 months post-surgery.
    Results.-The prevalence of CEH in our population was 15/70 (21.4%, 95% CI: 11.8% to 31.0%). The main clinical features were dull and tightening/pressing headache sensations in the occipital region. Headache severity was mild (VAS, 32611 mm) and only one patient reported use of an oral analgesic. Compared to patients without CEH, patients with CEH had higher frequencies of neck pain (86.7% vs. 50.9%; P=.017), cervical range of motion limitation (ROM) (66.7% vs. 38.2%; P=.049), and higher Neck Disability Index scores (14 vs. 3; P&lt;.001). Among the different cervical spine disorders, the prevalence of CEH was highest in cervical spondylotic myeloradiculopathy patients (60%), being &lt;= 20% for all other disorders. Surgical treatments including cervical laminoplasty to relieve abnormal pressure on the spinal cord via a posterior approach, were associated with initial improvements in headache VAS that slightly diminished by 12 months post-surgery (P&lt;.001).
    Conclusions.-We report a lower prevalence of CEH in patients with cervical spinal disorders requiring surgery than that reported previously. The main clinical features of CEH were mild, dull, and tightening/pressing headache sensations in the occipital region. Potential risk factors for CEH included neck pain, limited cervical ROM, high Neck Disability Index score, and a diagnosis of cervical spondylotic myeloradiculopathy. The further accumulation of patients in a multi-institutional study may be required in order to discuss the diagnostic criteria and pathophysiology of this condition.

    DOI: 10.1111/head.13123

    Web of Science

    PubMed

    researchmap

  • Multiple system atrophy: clinicopathological characteristics in Japanese patients Reviewed

    Tetsutaro Ozawa, Osamu Onodera

    PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES   93 ( 5 )   251 - 258   2017.5

     More details

    Language:English   Publisher:JAPAN ACAD  

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that has both clinical and pathological variants. Clinical examples include MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent pathological variants. We performed systematic reviews of studies that addressed the relative frequencies of clinical or pathological variants of MSA in various populations to determine the clinicopathological characteristics in Japanese MSA. The results revealed that the majority of Japanese patients have MSA-C, while the majority of patients in Europe and North America have MSA-P. A comparative study of MSA pathology showed that the olivopontocerebellar-predominant pathology was more frequent in Japanese MSA than in British MSA. Demonstrated differences in pathological subtype thus appear consistent with differences in the clinical subtype of MSA demonstrated between Japan and European populations. We concluded that olivopontocerebellar-predominant pathology and MSA-C may represent clinicopathological characteristics in Japanese MSA. Factors determining predominant involvement of olivopontocerebellar regions in MSA should therefore be explored.

    DOI: 10.2183/pjab.93.016

    Web of Science

    PubMed

    researchmap

  • [PRES: Posterior Reversible Encephalopathy Syndrome]. Reviewed

    Kouichirou Okamoto, Kunio Motohashi, Hidemoto Fujiwara, Tomohiko Ishihara, Itaru Ninomiya, Osamu Onodera, Yukihiko Fujii

    Brain and nerve = Shinkei kenkyu no shinpo   69 ( 2 )   129 - 141   2017.2

     More details

    Language:Japanese  

    Posterior reversible encephalopathy syndrome (PRES) is suggested in patients with acute neurological symptoms in the appropriate clinical context, including acute hypertension, blood pressure fluctuations, renal failure, blood transfusion, immunosuppression, autoimmune disorders, and eclampsia. PRES is a clinical syndrome, and refers to a disorder with reversible subcortical vasogenic brain edema caused by endothelial dysfunction, predominantly involving the bilateral parieto-occipital regions. Although the clinical course and prognosis are favorable in most cases, intracranial hemorrhage and/or restricted diffusion similar to acute infarction could be seen in some lesions on brain magnetic resonance imaging (MRI). The spinal cord may be involved in some patients with posterior fossa lesions. Understanding the pathophysiology of PRES is helpful in making the correct early diagnosis and selecting appropriate therapies to improve its clinical course and outcome. Differentiation of PRES from strokes is critical in the setting of a neurological emergency.

    DOI: 10.11477/mf.1416200653

    PubMed

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04871&link_issn=&doc_id=20170217120007&doc_link_id=10.11477%2Fmf.1416200653&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1416200653&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Characteristic Brain MRI Features of Manifesting Heterozygotes With Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

    Masahiro Uemura, Hiroaki Nozaki, Yumi Sekine, Ikuko Mizuta, Tomoko Noda, Kazuhide Miyazaki, Muichi Kaito, Yoshinori Nishimoto, Yutaka Shimoe, Akiko Shirata, Kiyomi Yamane, Sohei Yanagawa, Mikio Hirayama, Masato Tamura, Toshiki Mizuno, Masatoyo Nishizawa, Osamu Onodera

    STROKE   48   2017.2

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: Multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions Reviewed

    Haishan Jiang, Hiroshi Shimizu, Atsushi Shiga, Masami Tanaka, Osamu Onodera, Akiyoshi Kakita, Hitoshi Takahashi

    NEUROPATHOLOGY   37 ( 1 )   69 - 77   2017.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    We previously reported familial amyotrophic lateral sclerosis (FALS) of 11years duration in a 57-year-old woman, who received artificial ventilation for 5years prior to death and exhibited widespread multisystem degeneration and neurofilamentous aggregates, so-called conglomerate inclusions (CIs). In the present study, we re-evaluated this autopsied patient (proband) with further immunohistochemical observation as well as mutational analysis of the superoxide dismutase 1 (SOD1) gene. A review of the clinical features of the proband's family revealed five affected members (including the proband) over two successive generations who showed marked variability in clinical presentation, such as the age at onset. The proband was found to harbor a heterozygous missense mutation in exon 4 (I104F) of the SOD1 gene. In the brain and spinal cord, SOD1-positive neuronal cytoplasmic inclusions (NCIs) were found to be more widely distributed than CIs, the latter being weakly positive for SOD1. No Lewy body-like hyaline inclusions were found. This is considered to be the first description of an autopsy case of FALS with an I104F SOD1 gene mutation, suggesting that combination of marked intra-familial clinical variability and multisystem degeneration with occurrence of CIs and SOD1-positive NCIs is a characteristic feature of FALS with this SOD1 gene mutation.

    DOI: 10.1111/neup.12324

    Web of Science

    PubMed

    researchmap

  • Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats Reviewed

    Masato Kanazawa, Minami Miura, Masafumi Toriyabe, Misaki Koyama, Masahiro Hatakeyama, Masanori Ishikawa, Takashi Nakajima, Osamu Onodera, Tetsuya Takahashi, Masatoyo Nishizawa, Takayoshi Shimohata

    SCIENTIFIC REPORTS   7   42582   2017.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Cell-therapies that invoke pleiotropic mechanisms may facilitate functional recovery in stroke patients. We hypothesized that a cell therapy using microglia preconditioned by optimal oxygen-glucose deprivation (OGD) is a therapeutic strategy for ischemic stroke because optimal ischemia induces anti-inflammatory M2 microglia. We first delineated changes in angiogenesis and axonal outgrowth in the ischemic cortex using rats. We found that slight angiogenesis without axonal outgrowth were activated at the border area within the ischemic core from 7 to 14 days after ischemia. Next, we demonstrated that administration of primary microglia preconditioned by 18 hours of OGD at 7 days prompted functional recovery at 28 days after focal cerebral ischemia compared to control therapies by marked secretion of remodelling factors such as vascular endothelial growth factor, matrix metalloproteinase-9, and transforming growth factor-beta polarized to M2 microglia in vitro/vivo. In conclusion, intravascular administration of M2 microglia preconditioned by optimal OGD may be a novel therapeutic strategy against ischemic stroke.

    DOI: 10.1038/srep42582

    Web of Science

    PubMed

    researchmap

  • Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation Reviewed

    T. Konno, K. Yoshida, T. Mizuno, T. Kawarai, M. Tada, H. Nozaki, S. I. Ikeda, M. Nishizawa, O. Onodera, Z. K. Wszolek, T. Ikeuchi

    European Journal of Neurology   24 ( 1 )   37 - 45   2017.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blackwell Publishing Ltd  

    Background and purpose: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. Methods: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. Results: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18–78 years), the mean age at death was 53 years (range 23–84 years) and the mean disease duration was 6.8 years (range 1–29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158–11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype−genotype correlations. Conclusions: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.

    DOI: 10.1111/ene.13125

    Scopus

    PubMed

    researchmap

  • Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) Reviewed

    Masahiro Uemura, Hiroaki Nozaki, Osamu Onodera

    Brain and Nerve   69 ( 1 )   25 - 33   2017.1

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Igaku-Shoin Ltd  

    Cerebral small vessel disease (CSVD) is frequently observed among the elderly and is known to cause dementia and gait disturbance associated with white matter lesions, lacunar infarcts, and cerebral hemorrhage. Molecular mechanistic studies promise to provide new insights into the pathogenesis of hereditary CSVD. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is one of the hereditary CSVDs caused by a mutation in the hightemperature requirement serine peptidase A1 (HTRA1) gene. The loss of HTRA1 protease activity increases signaling via transforming growth factor (TGF)β, thereby resulting in CARASIL. Although the CARASIL has been characterized by juvenile onset alopecia and spondylosis deformans, these features are not always observed in individuals with an HTRA1 mutation. Moreover, some HTRA1 mutations cause CSVD in heterozygous states. Therefore, the clinical features of CSVD resulting from an HTRA1 mutation extend to patients with CSVD alone or to those with dominantly inherited CSVD.

    DOI: 10.11477/mf.1416200631

    Scopus

    PubMed

    researchmap

  • Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation Reviewed

    T. Konno, K. Yoshida, T. Mizuno, T. Kawarai, M. Tada, H. Nozaki, S. -I. Ikeda, M. Nishizawa, O. Onodera, Z. K. Wszolek, T. Ikeuchi

    EUROPEAN JOURNAL OF NEUROLOGY   24 ( 1 )   37 - 45   2017.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Background and purpose: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated.
    Methods: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data.
    Results: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype similar to genotype correlations.
    Conclusions: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.

    DOI: 10.1111/ene.13125

    Web of Science

    PubMed

    researchmap

  • Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Reviewed

    T. Konno, D. F. Broderick, N. Mezaki, A. Isami, D. Kaneda, Y. Tashiro, T. Tokutake, B. M. Keegan, B. K. Woodruff, T. Miura, H. Nozaki, M. Nishizawa, O. Onodera, Z. K. Wszolek, T. Ikeuchi

    AMERICAN JOURNAL OF NEURORADIOLOGY   38 ( 1 )   77 - 83   2017.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC NEURORADIOLOGY  

    Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.

    DOI: 10.3174/ajnr.A4938

    Web of Science

    PubMed

    researchmap

  • A CARASIL Patient from Americas with Novel Mutation and Atypical Features: Case Presentation and Literature Review Reviewed

    Muhammad Ibrahimi, Hiroaki Nozaki, Angelica Lee, Osamu Onodera, Raymond Reichwein, Matthew Wicklund, Mohammad El-Ghanem

    CEREBROVASCULAR DISEASES   44 ( 3-4 )   135 - 140   2017

     More details

    Language:English   Publisher:KARGER  

    Objective: Reporting a novel mutation in the HTRA1 gene in a CARASIL patient from Americas. Methods: Clinical presentation and neuroimaging were consistent with CARASIL. HTRA1 DNA sequencing was performed using advanced ("next generation") sequencing technology. The results revealed a homozygous missense mutation as c.616G&gt;A (p.Gly206Arg) in the HTRA1 gene. Results: A 24-year-old man with a history of chronic back pain presented with recurrent ischemic strokes. A diagnosis of CARASIL was made with the finding of a novel homozygous missense mutation c.616G&gt;A in HTRA1 gene, resulting in change from Glycine to Arginine in the Serine Protease HTRA1. Brain imaging showed multiple lacunar infarcts with extensive abnormalities of the white matter that spared the external capsules. He also had unilateral decreased hearing with craniofacial asymmetry. None of the above features have been previously described in known CARASIL patients. Both parents of the proband were heterozygous for the same missense mutation. Conclusion: We discovered a novel missense mutation (c.616G&gt;A) associated with a phenotype of CARASIL. This is the first genetically backed case of CARASIL in the new world. The patient's craniofacial abnormalities, including asymmetry of the head, may be related to impaired modulation of transforming growth factor-beta 1, the result of loss of proteolytic activity of HTRA1. External capsules remained unaffected, despite findings of advanced changes in the rest of the cerebral white matter. Literature is briefly reviewed. The patient's history, neurological exam, neuroimaging, and genetic testing are included. (C) 2017 S. Karger AG, Basel

    DOI: 10.1159/000477358

    Web of Science

    PubMed

    researchmap

  • Dissociation between intact vibratory sensation and impaired joint position sensation may predict ataxia of spinal origin Reviewed

    Masato Kanazawa, Keiichi Katsumi, Takayoshi Tokutake, Naoto Endo, Osamu Onodera, Masatoyo Nishizawa

    Interdisciplinary Neurosurgery: Advanced Techniques and Case Management   6   68 - 70   2016.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier B.V.  

    Vibratory and joint position sensations are usually impaired simultaneously and afferents for both sensations ascend the dorsal columns. There are a few evidences that the central pathways in the spinal cord for position and vibratory sensations are not identical. In this study, we examined the clinical features of patients with sensory impairments of vibratory and joint position sensations. According to 43 evaluated patients’ results, the dissociation between an intact vibratory sensation and impaired joint position sensation may be important for the diagnosis of spinal disorders. We also report three cases of patients with spinal ataxia caused by sensory impairments and who show the dissociation between an impaired joint position sensation and an intact vibratory sensation. The combination of intact vibration sensation and impaired joint position sensation may suggest a dorsal column lesion in the spinal cord.

    DOI: 10.1016/j.inat.2016.09.003

    Web of Science

    Scopus

    researchmap

    Other Link: http://orcid.org/0000-0001-6337-8156

  • Performance of a real-time PCR-based approach and droplet digital PCR in detecting human parechovirus type 3 RNA Reviewed

    Yuta Aizawa, Akihide Koyama, Tomohiko Ishihara, Osamu Onodera, Akihiko Saitoh

    JOURNAL OF CLINICAL VIROLOGY   84   27 - 31   2016.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Background: Human parechovirus type 3 (HPeV3) is an emerging virus that causes sepsis and meningoencephalitis in neonates and young infants. Correct diagnosis of HPeV3 infection is critical in determining appropriate management and predicting patients' clinical course. Real-time reverse transcription PCR (RT-PCR) analysis of serum and/or cerebrospinal fluid (CSF) has been used to diagnose HPeV3 infection; however, the assay detection limits have not been fully evaluated.
    Objectives: We tested the hypothesis that droplet digital RT-PCR (RT-ddPCR) a novel technique that precisely quantitates low-copy target genes by diluting and partitioning samples into compartments increases the detection rate of HPeV3 RNA as compared with real-time RT-PCR.
    Study design: Using samples with predetermined HPeV3 copy numbers, we evaluated one-step and two-step RT-ddPCR. Then, we tested two-step RT-ddPCR and real-time RT-PCR, using clinical samples with low copy numbers. Finally, we used two-step RT-ddPCR to evaluate clinical samples obtained from HPeV3-infected patients with positive serum but negative CSF, as determined by real-time RT-PCR.
    Results: Two-step RT-ddPCR was less variable and more specific than one-step RT-ddPCR. Two-step RT-ddPCR detected HPeV3 RNA in all six CSF samples; four samples (67%) were reproducibly positive and the other two samples (33%) were positive at least once in four replicates. Finally, no nonspecific droplet was positive by two-step RT-ddPCR.
    Conclusions: Two-step RT-ddPCR may enhance the rate of HPeV3 RNA detection from samples with low viral loads, thereby improving diagnosis and management of HPeV3-infected patients. (C) 2016 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jcv.2016.09.009

    Web of Science

    PubMed

    researchmap

  • Clinical Characterization of Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Reviewed

    Takuya Konno, Kunihiro Yoshida, Toshiki Mizuno, Toshitaka Kawarai, Masayoshi Tada, Hiroaki Nozaki, Shu-ichi Ikeda, Masatoyo Nishizawa, Osamu Onodera, Zbigniew K. Wszolek, Takeshi Ikeuchi

    ANNALS OF NEUROLOGY   80   S194 - S194   2016.10

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Web of Science

    researchmap

  • Characteristic Microglial Features in Patients with Hereditary Diffuse Leukoencephalopathy with Spheroids Reviewed

    Mari Tada, Takuya Konno, Masayoshi Tada, Toshiyuki Tezuka, Takeshi Miura, Naomi Mezaki, Ken-ichi Okazaki, Musashi Arakawa, Kyoko Itoh, Toru Yamamoto, Hideaki Yokoo, Nobuaki Yoshikura, Kenji Ishihara, Masao Horie, Hirohide Takebayashi, Yasuko Toyoshima, Makoto Naito, Osamu Onodera, Masatoyo Nishizawa, Hitoshi Takahashi, Takeshi Ikeuchi, Akiyoshi Kakita

    ANNALS OF NEUROLOGY   80 ( 4 )   554 - 565   2016.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Objective: To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R).
    Methods: We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed.
    Results: In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow.
    Interpretation: The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations.

    DOI: 10.1002/ana.24754

    Web of Science

    PubMed

    researchmap

  • Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V) Reviewed

    Kentaro Hayashi, Yoko Mochizuki, Ryoko Takeuchi, Toshio Shimizu, Masahiro Nagao, Kazuhiko Watabe, Nobutaka Arai, Kiyomitsu Oyanagi, Osamu Onodera, Masaharu Hayashi, Hitoshi Takahashi, Akiyoshi Kakita, Eiji Isozaki

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   4 ( 1 )   107   2016.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOMED CENTRAL LTD  

    In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.

    DOI: 10.1186/s40478-016-0379-3

    Web of Science

    PubMed

    researchmap

  • Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes Reviewed

    Ryoko Takeuchi, Mari Tada, Atsushi Shiga, Yasuko Toyoshima, Takuya Konno, Tomoe Sato, Hiroaki Nozaki, Taisuke Kato, Masao Horie, Hiroshi Shimizu, Hirohide Takebayashi, Osamu Onodera, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   4 ( 1 )   61   2016.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOMED CENTRAL LTD  

    Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype.

    DOI: 10.1186/s40478-016-0335-2

    Web of Science

    PubMed

    researchmap

  • Proposed Diagnostic Criteria for Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Reviewed

    Takuya Konno, Kunihiro Yoshida, Toshiki Mizuno, Toshitaka Kawarai, Masayoshi Tada, Hiroaki Nozaki, Shu-Ichi Ikeda, Masatoyo Nishizawa, Osamu Onodera, Zbigniew Wszolek, Takeshi Ikeuchi

    NEUROLOGY   86   2016.4

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias Reviewed

    Masayoshi Tada, Masatoyo Nishizawa, Osamu Onodera

    NEUROCHEMISTRY INTERNATIONAL   94   1 - 8   2016.3

     More details

    Language:English   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    Modulation of the intracellular calcium concentration is a ubiquitous signaling system involved in the control of numerous biological processes in a wide variety of cells. Inositol 1,4,5-trisphosphate (IP3) receptors (IP(3)Rs), which act as calcium release channels in the ER membrane, play a key role in the regulation of intracellular calcium concentration. IP3R type 1 (IP(3)R1) is the major neuronal IP3R isoform in the central nervous system and particularly abundant in cerebellar Purkinje cells. Heterozygous deletions or missense mutations in ITPR1, which encodes IP(3)R1, result in autosomal dominantly inherited spinocerebellar ataxias (SCAs), including SCA types 15 (SCA15) and 29 (SCA29). In addition, homozygous missense mutations in carbonic anhydrase-related protein VIII (CARP), which suppresses the ability of IP3 to bind to IP(3)R1, cause a recessively inherited ataxia with mild cognitive impairment with/without quadrupedal gait. Moreover, cytosolic calcium overload with excessive IP(3)R1 activity has been implicated in the pathogenesis of other SCAs, including SCA types 2 (SCA2) and 3 (SCA3). These facts indicate that dysregulation of IP3R-mediated calcium signaling is linked to the pathogenesis of SCAs. Here, we focus on the molecular basis of SCA15 and SCA29, which are caused by mutations in ITPR1. In addition, we discuss other SCAs whose pathogenesis may be linked to aberrant activation of IP3R-mediated Ca2+ signaling. (C) 2016 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuint.2016.01.007

    Web of Science

    PubMed

    researchmap

  • Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology Reviewed

    Yuichi Yokoyama, Yasuko Toyoshima, Atsushi Shiga, Mari Tada, Hideaki Kitamura, Kazuko Hasegawa, Osamu Onodera, Takeshi Ikeuchi, Toshiyuki Someya, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    BRAIN PATHOLOGY   26 ( 2 )   155 - 166   2016.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Progressive supranuclear palsy (PSP) is a four-repeat tauopathy with tau-positive, argyrophilic tuft-shaped astrocytes (TAs). We performed a pathological and clinical investigation in 40 consecutive autopsied Japanese patients with pathological diagnoses of PSP or PSP-like disease. Unequivocal TAs were present in 22 cases, all of which were confirmed to be PSP. Such TAs were hardly detected in the other 18 cases, which instead exhibited tau-positive, argyrophilic astrocytes, appearing as comparatively small clusters with central nuclei of irregularly shaped, coarse structures (equivocal TAs). Cluster analysis of the distribution pattern of tau-related pathology for these 18 cases identified two subgroups, pallido-nigro-luysian atrophy (PNLA) Type 1 (n=9) and Type 2 (n=9), the former being distinguished from the latter by the presence of tau-related lesions in the motor cortex, pontine nucleus and cerebellar dentate nucleus in addition to the severely affected PNL system. The duration from symptom onset until becoming wheelchair-bound was significantly longer in PNLAType 1. Immunoblotting of samples from the three disease conditions revealed band patterns of low-molecular-mass tau fragments at approximate to 35kDa. These findings shed further light on the wide pathological and clinical spectrum of four-repeat tauopathy, representing PSP in the broad sense rather than classical PSP.

    DOI: 10.1111/bpa.12265

    Web of Science

    PubMed

    researchmap

  • Modifiable Factors Associated with Cognitive Impairment in 1,143 Japanese Outpatients: The Project in Sado for Total Health (PROST) Reviewed

    Kaori Kitamura, Yumi Watanabe, Kazutoshi Nakamura, Kazuhiro Sanpei, Minako Wakasugi, Akio Yokoseki, Osamu Onodera, Takeshi Ikeuchi, Ryozo Kuwano, Takeshi Momotsu, Ichiei Narita, Naoto Endo

    Dementia and Geriatric Cognitive Disorders Extra   6 ( 2 )   341 - 349   2016

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:S. Karger AG  

    Background/Aims: Evidence on modifiable factors associated with cognitive impairment in Japanese patients is scarce. This study aimed to determine modifiable factors for cognitive impairment in a Japanese hospital-based population. Methods: Subjects of this cross-sectional study were 1,143 patients of Sado General Hospital (Niigata, Japan) registered in the Project in Sado for Total Health (PROST) between June 2008 and September 2014. We assessed disease history, body mass index (BMI), leisure time physical activity, walking time, smoking and drinking habits, and consumption of vegetables, fruits, and green tea as predictors, with cognitive impairment defined by the Mini-Mental State Examination (score &lt
    24) as an outcome. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) for cognitive impairment. Results: The mean subject age was 68.9 years, and the prevalence of cognitive impairment was 21.5%. Multivariate analysis revealed that age (p &lt
    0.001), low BMI (&lt
    21.1
    OR 1.39, 95% CI 1.12-1.72), a history of stroke (p = 0.003), a history of myocardial infarction (p = 0.038), low fruit consumption (p for trend = 0.012), and low green tea consumption (p for trend = 0.032) were independently associated with a higher prevalence of cognitive impairment. Conclusions: Modifiable factors, such as low BMI, low fruit consumption, and low green tea consumption, are associated with cognitive impairment. Longitudinal studies will be needed to confirm these findings.

    DOI: 10.1159/000447963

    Scopus

    PubMed

    researchmap

  • Elevated C-Reactive Protein Is Associated with Cognitive Decline in Outpatients of a General Hospital: The Project in Sado for Total Health (PROST) Reviewed

    Yumi Watanabe, Kaori Kitamura, Kazutoshi Nakamura, Kazuhiro Sanpei, Minako Wakasugi, Akio Yokoseki, Osamu Onodera, Takeshi Ikeuchi, Ryozo Kuwano, Takeshi Momotsu, Ichiei Narita, Naoto Endo

    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS EXTRA   6 ( 1 )   10 - 19   2016

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:KARGER  

    Background/Aims: We aimed to determine whether the concentration of serum C-reactive protein (CRP) is associated with cognitive function in an adult Japanese population. Methods: Participants of this cross-sectional study were from a subgroup of the Project in Sado for Total Health (PROST; n = 454; mean age, 70.5 years). The cognitive state was evaluated using the Mini-Mental State Examination (MMSE), and those with an MMSE score <24 were considered 'cognitively declined'. Concentrations of serum high-sensitivity CRP were measured. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for cognitive decline, adjusting for the covariates of age, sex, BMI, disease history, and APOE allele. Results: Of the 454 participants, 94 (20.7%) were cognitively declined. Relative to the lowest (first) quartile of CRP concentration, adjusted ORs were 1.29 (95% CI 0.61-2.75) for the second, 1.78 (95% CI 0.82-3.86) for the third, and 3.05 (95% CI 1.45-6.42) for the highest (fourth) quartiles (p for trend = 0.018). When data were stratified by sex, the association between CRP concentration and cognitive decline was observed only in women. Conclusion: Our findings suggest an association between higher CRP concentration and lower cognitive function. Chronic inflammation may affect cognitive function in adults, in particular women. (C) 2016 The Author(s) Published by S. Karger AG, Basel

    DOI: 10.1159/000442585

    Web of Science

    Scopus

    PubMed

    researchmap

  • Redefining cerebellar ataxia in degenerative ataxias: lessons from recent research on cerebellar systems Reviewed

    Masayoshi Tada, Masatoyo Nishizawa, Osamu Onodera

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   86 ( 8 )   922 - 928   2015.8

     More details

    Language:English   Publisher:BMJ PUBLISHING GROUP  

    Recent advances in our understanding of neurophysiological functions in the cerebellar system have revealed that each region involved in degenerative ataxias contributes differently. To regulate voluntary movements, the cerebellum forms internal models within its neural circuits that mimic the behaviour of the sensorimotor system and objects in the external environment. The cerebellum forms two different internal models: forward and inverse. The forward model is formed by efference copy signals conveyed by the corticopontocerebellar system, and it derives the estimated consequences for action. The inverse model describes sequences of motor commands to accomplish an aim. During motor learning, we improve internal models by comparing the estimated consequence of an action from the forward model with the actual consequence of the action produced by the inverse model. The functions of the cerebellum encompass the formation, storage and selection of internal models. Considering the neurophysiological properties of the cerebellar system, we have classified degenerative ataxias into four types depending on which system is involved: Purkinje cells, the corticopontocerebellar system, the spinocerebellar system and the cerebellar deep nuclei. With regard to their respective contributions to the internal models, we speculate that loss of Purkinje cells leads to malformation of the internal models, whereas disturbance of the afferent system, corticopontocerebellar system or spinocerebellar system leads to mis-selection of the proper internal model. An understanding of the pathophysiological properties of ataxias in each degenerative ataxia enables the development of new methods to evaluate ataxias.

    DOI: 10.1136/jnnp-2013-307225

    Web of Science

    PubMed

    researchmap

  • Variants associated with Gaucher disease in multiple system atrophy Reviewed

    Jun Mitsui, Takashi Matsukawa, Hidenao Sasaki, Ichiro Yabe, Masaaki Matsushima, Alexandra Duerr, Alexis Brice, Hiroshi Takashima, Akio Kikuchi, Masashi Aoki, Hiroyuki Ishiura, Tsutomu Yasuda, Hidetoshi Date, Budrul Ahsan, Atsushi Iwata, Jun Goto, Yaeko Ichikawa, Yasuo Nakahara, Yoshio Momose, Yuji Takahashi, Kenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Takamichi Hattori, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Tomoyoshi Kondo, Shigeo Murayama, Nobutaka Hattori, Mitsutoshi Yamamoto, Miho Murata, Wataru Satake, Tatsushi Toda, Alessandro Filla, Thomas Klockgether, Ullrich Wuellner, Garth Nicholson, Sid Gilman, Caroline M. Tanner, Walter A. Kukull, Mathew B. Stern, Virginia M. -Y. Lee, John Q. Trojanowski, Eliezer Masliah, Phillip A. Low, Paola Sandroni, Laurie J. Ozelius, Tatiana Foroud, Shoji Tsuji

    ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY   2 ( 4 )   417 - 426   2015.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10(-3)). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

    DOI: 10.1002/acn3.185

    Web of Science

    PubMed

    researchmap

  • Conformational disease and rna disease theory in the context of neurodegenerative diseases

    Tomohiko, I., Osamu, O.

    Neurodegenerative Disorders as Systemic Diseases   2015

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Neurodegenerative Disorders as Systemic Diseases  

    DOI: 10.1007/978-4-431-54541-5_1

    Scopus

    researchmap

  • Features of Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (vol 45, pg 3447, 2014) Reviewed

    Nozaki

    STROKE   45 ( 11 )   E237 - E237   2014.11

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1161/STR.0000000000000044

    Web of Science

    PubMed

    researchmap

  • C9ORF72 repeat-associated non-ATG-translated polypeptides are distributed independently of TDP-43 in a Japanese patient with c9ALS Reviewed

    T. Konno, M. Tada, A. Shiga, A. Tsujino, H. Eguchi, M. Masuda-Suzukake, M. Hasegawa, M. Nishizawa, O. Onodera, A. Kakita, H. Takahashi

    NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY   40 ( 6 )   783 - 788   2014.10

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    DOI: 10.1111/nan.12157

    Web of Science

    PubMed

    researchmap

  • A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease Reviewed

    Gen Tamiya, Satoshi Makino, Makiko Hayashi, Akiko Abe, Chikahiko Numakura, Masao Ueki, Atsushi Tanaka, Chizuru Ito, Kiyotaka Toshimori, Nobuhiro Ogawa, Tomoya Terashima, Hiroshi Maegawa, Daijiro Yanagisawa, Ikuo Tooyama, Masayoshi Tada, Osamu Onodera, Kiyoshi Hayasaka

    AMERICAN JOURNAL OF HUMAN GENETICS   95 ( 3 )   294 - 300   2014.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6de1CACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT.

    DOI: 10.1016/j.ajhg.2014.07.013

    Web of Science

    PubMed

    researchmap

  • Bunina bodies in motor and non-motor neurons revisited: A pathological study of an ALS patient after long-term survival on a respirator Reviewed

    Tadashi Kimura, Haishan Jiang, Takuya Konno, Makiko Seto, Keisuke Iwanaga, Mitsuhiro Tsujihata, Akira Satoh, Osamu Onodera, Akiyoshi Kakita, Hitoshi Takahashi

    NEUROPATHOLOGY   34 ( 4 )   392 - 397   2014.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72 mutation, of 12 years duration in a 75-year-old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non-motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP-43 inclusions.

    DOI: 10.1111/neup.12105

    Web of Science

    PubMed

    researchmap

  • Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of Japanese patients with novel SCARB2 mutations Reviewed

    Y. -J. Fu, I. Aida, M. Tada, M. Tada, Y. Toyoshima, S. Takeda, T. Nakajima, H. Naito, M. Nishizawa, O. Onodera, A. Kakita, H. Takahashi

    NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY   40 ( 5 )   551 - 563   2014.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Aims: Mutations in the SCARB2 gene cause a rare autosomal recessive disease, progressive myoclonus epilepsy (PME) with or without renal failure, the former also being designated action myoclonus-renal failure syndrome. Although reported cases have been accumulating, only a few have described its neuropathology. We studied two Japanese patients with PME without renal failure, in whom the ages at onset and disease durations were 45 and 20 years, and 14 and 8.5 years respectively. Methods: Sequencing and restriction analysis of the SCARB2 gene and neuropathological examination with immunohistochemistry were performed. Results: Gene analyses revealed novel homozygous frameshift and nonsense mutations in the SCARB2 gene. Both cases exhibited deposition of brown pigment in the brain, especially the cerebellar and cerebral cortices. Ultrastructurally, the pigment granules were localized in astrocytes. Neuronal loss and gliosis were also evident in the brain, including the pallidoluysian and cerebello-olivary systems. The spinal cord was also affected. Such changes were less severe in one patient with late-onset disease than in the other patient with early-onset disease. In brain and kidney sections, immunostaining with an antibody against the C-terminus of human SCARB2 revealed decreased levels and no expression of the protein respectively. Conclusions: The frameshift mutation detected in the patient with late-onset disease is a hitherto undescribed, unique type of SCARB2 gene mutation. The present two patients are the first reported to have clearly demonstrated both extraneuronal brown pigment deposition and system neurodegeneration as neuropathological features of PME with SCARB2 mutations.

    DOI: 10.1111/nan.12057

    Web of Science

    PubMed

    researchmap

  • A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan Reviewed

    Kenichi Yasui, Ichiro Yabe, Kunihiro Yoshida, Kazuaki Kanai, Kimihito Arai, Mizuki Ito, Osamu Onodera, Shigeru Koyano, Eiji Isozaki, Setsu Sawai, Yoshiki Adachi, Hidenao Sasaki, Satoshi Kuwabara, Takamichi Hattori, Gen Sobue, Hidehiro Mizusawa, Shoji Tsuji, Masatoyo Nishizawa, Kenji Nakashima

    ORPHANET JOURNAL OF RARE DISEASES   9   118   2014.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOMED CENTRAL LTD  

    Background: Only a few prospective studies have determined which clinical symptoms and factors are associated with the disease severity of spinocerebellar ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to clarify both the natural history of SCA6 in Japan and the factors influencing disease progression.Methods: Patients were consecutively recruited between 2007 and 2008. Scores from the Scale for the Assessment and Rating of Ataxia (SARA) and Barthel Index (BI) were collected prospectively each year. Additionally, data from the Japan intractable diseases research (IDR) registry were collected both retrospectively, from 2003 to 2006, and prospectively, from 2007 to 2010. As a result, we were able to collect 3 years of retrospective data and 4 years of prospective data during the course of 3 yearly visits.Results: Forty-six patients were registered. The follow-up rate of the third year was 93%. The SARA scores worsened significantly each year. Over 3 years, the decline of the SARA scores was 1.33 +/- 1.40 points/year. The results of multivariate analysis of the decline of the SARA score were not significant. The IDR scores correlated well with the SARA and BI scores. Kaplan-Meier curves of 7 years of data from the IDR registry illustrated the correlation between the ability to walk and the time course of the disease.Conclusions: Information regarding the progression of ataxia and the decline in the activities of daily living (ADL) in patients with SCA6 was obtained by a 3-year cohort study and a 7-year IDR study. The decline of the SARA score of patients with SCA6 was 1.33 +/- 1.40 points/year. The results elucidate the natural history of SCA6, factors influencing disease severity, and utility of data from the IDR registry of Japan.

    DOI: 10.1186/s13023-014-0118-4

    Web of Science

    PubMed

    researchmap

  • A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories Reviewed

    Chizuru Akimoto, Alexander E. Volk, Marka van Blitterswijk, Marleen Van den Broeck, Claire S. Leblond, Serge Lumbroso, William Camu, Birgit Neitzel, Osamu Onodera, Wouter van Rheenen, Susana Pinto, Markus Weber, Bradley Smith, Melanie Proven, Kevin Talbot, Pamela Keagle, Alessandra Chesi, Antonia Ratti, Julie van der Zee, Helena Alstermark, Anna Birve, Daniela Calini, Angelica Nordin, Daniela C. Tradowsky, Walter Just, Hussein Daoud, Sabrina Angerbauer, Mariely DeJesus-Hernandez, Takuya Konno, Anjali Lloyd-Jani, Mamede de Carvalho, Kevin Mouzat, John E. Landers, Jan H. Veldink, Vincenzo Silani, Aaron D. Gitler, Christopher E. Shaw, Guy A. Rouleau, Leonard H. van den Berg, Christine Van Broeckhoven, Rosa Rademakers, Peter M. Andersen, Christian Kubisch

    JOURNAL OF MEDICAL GENETICS   51 ( 6 )   419 - 424   2014.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMJ PUBLISHING GROUP  

    Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories.
    Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference.
    Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories.
    Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.

    DOI: 10.1136/jmedgenet-2014-102360

    Web of Science

    PubMed

    researchmap

  • Minor splicing pathway is not minor any more: Implications for the pathogenesis of motor neuron diseases Reviewed

    Osamu Onodera, Tomohiko Ishihara, Atsushi Shiga, Yuko Ariizumi, Akio Yokoseki, Masatoyo Nishizawa

    NEUROPATHOLOGY   34 ( 1 )   99 - 107   2014.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    To explore the molecular pathogenesis of amyotrophic lateral sclerosis (ALS), the nuclear function of TAR-DNA binding protein 43kDa (TDP-43) must be elucidated. TDP-43 is a nuclear protein that colocalizes with Cajal body or Gem in cultured cells. Several recent studies have reported that the decreasing number of Gems accompanied the depletion of the causative genes for ALS, TDP-43 and FUS. Gems play an important role in the pathogenesis of spinal muscular atrophy. Gems are the sites of the maturation of spliceosomes, which are composed of uridylate-rich (U) snRNAs (small nuclear RNAs) and protein complex, small nuclear ribonuclearprotein (snRNP). Spliceosomes regulate the splicing of pre-mRNA and are classified into the major or minor classes, according to the consensus sequence of acceptor and donor sites of pre-mRNA splicing. Although the major class of spliceosomes regulates most pre-mRNA splicing, minor spliceosomes also play an important role in regulating the splicing or global speed of pre-mRNA processing. A mouse model of spinal muscular atrophy, in which the number of Gems is decreased, shows fewer subsets U snRNAs. Interestingly, in the central nervous system, U snRNAs belonging to the minor spliceosomes are markedly reduced. In ALS, the U12 snRNA is decreased only in the tissue affected by ALS and not in other tissues. Although the molecular mechanisms underlying the decreased U12 snRNA resulting in cell dysfunction and cell death in motor neuron diseases remain unclear, these findings suggest that the disturbance of nuclear bodies and minor splicing may underlie the common molecular pathogenesis of motor neuron diseases.

    DOI: 10.1111/neup.12070

    Web of Science

    PubMed

    researchmap

  • IP3 receptors in neurodegenerative disorders: Spinocerebellar ataxias and Huntington’s and Alzheimer’s diseases Reviewed

    Masayoshi Tada, Masatoyo Nishizawa, Osamu Onodera

    Pathologies of Calcium Channels   579 - 600   2014.1

     More details

    Language:English   Publishing type:Part of collection (book)   Publisher:Springer Berlin Heidelberg  

    Modulation of intracellular calcium concentration is a ubiquitous signaling system involved in numerous biological processes in diverse cell types. Alterations of intracellular calcium homeostasis have been implicated in age-related neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and spinocerebellar ataxias (SCAs). Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), calcium release channels in the ER membrane, play a key role in regulating intracellular calcium concentration. IP3R type 1 (IP3R1), a major neuronal type of IR3R, is expressed ubiquitously and is involved in diverse biological processes. Cerebellar Purkinje cells are mainly affected by alterations in IP3R1. Heterozygous deletion or missense mutations in ITPR1, the IP3R1 gene, result in autosomal dominantly inherited ataxias, including SCA type 15 or 29. In addition, mutations in carbonic anhydrase-related protein VIII, which suppresses the binding ability of IP3to IP3R1, cause recessively, inherited ataxia. These results indicate that IP3R1-mediated calcium signaling has an important role in maintaining the function of Purkinje cells. Moreover, cytosolic calcium overload with excessive IP3R1 activity has been implicated in pathogenesis of other neurodegenerative diseases, including SCA type 2, SCA type 3, Huntington’s disease, and Alzheimer’s disease, where dysregulation of IP3R1-mediated calcium signaling may link to the pathogenesis.

    DOI: 10.1007/978-3-642-40282-1_28

    Scopus

    researchmap

  • Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS Reviewed

    Takuya Konno, Masayoshi Tada, Mari Tada, Akihide Koyama, Hiroaki Nozaki, Yasuo Harigaya, Jin Nishimiya, Akiko Matsunaga, Nobuaki Yoshikura, Kenji Ishihara, Musashi Arakawa, Aiko Isami, Kenichi Okazaki, Hideaki Yokoo, Kyoko Itoh, Makoto Yoneda, Mitsuru Kawamura, Takashi Inuzuka, Hitoshi Takahashi, Masatoyo Nishizawa, Osamu Onodera, Akiyoshi Kakita, Takeshi Ikeuchi

    NEUROLOGY   82 ( 2 )   139 - 148   2014.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Objective:To clarify the genetic, clinicopathologic, and neuroimaging characteristics of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) with the colony stimulating factor 1 receptor (CSF-1R) mutation.Methods:We performed molecular genetic analysis of CSF-1R in patients with HDLS. Detailed clinical and neuroimaging findings were retrospectively investigated. Five patients were examined neuropathologically.Results:We found 6 different CSF-1R mutations in 7 index patients from unrelated Japanese families. The CSF-1R mutations included 3 novel mutations and 1 known missense mutation at evolutionarily conserved amino acids, and 1 novel splice-site mutation. We identified a novel frameshift mutation. Reverse transcription PCR analysis revealed that the frameshift mutation causes nonsense-mediated mRNA decay by generating a premature stop codon, suggesting that haploinsufficiency of CSF-1R is sufficient to cause HDLS. Western blot analysis revealed that the expression level of CSF-1R in the brain from the patients was lower than from control subjects. The characteristic MRI findings were the involvement of the white matter and thinning of the corpus callosum with signal alteration, and sequential analysis revealed that the white matter lesions and cerebral atrophy relentlessly progressed with disease duration. Spotty calcifications in the white matter were frequently observed by CT. Neuropathologic analysis revealed that microglia in the brains of the patients demonstrated distinct morphology and distribution.Conclusions:These findings suggest that patients with HDLS, irrespective of mutation type in CSF-1R, show characteristic clinical and neuroimaging features, and that perturbation of CSF-1R signaling by haploinsufficiency may play a role in microglial dysfunction leading to the pathogenesis of HDLS.

    DOI: 10.1212/WNL.0000000000000046

    Web of Science

    PubMed

    researchmap

  • Aberration of the spliceosome in amyotrophic lateral sclerosis Reviewed

    Tomohiko Ishihara, Akiyoshi Kakita, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa

    Clinical Neurology   54 ( 12 )   1155 - 1157   2014

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)   Publisher:Societas Neurologica Japonica  

    TDP-43 is a nuclear protein that plays a role in RNA metabolism, and its dysfunction has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a typical adult-onset motor neuron disease. We investigated RNA metabolism in relation to TDP-43 function in neuronal tissues affected by ALS, and found a decrease in the number of nuclear GEM bodies, as well as reduced expression of minor spliceosomes, which are functional RNA-protein complexes. Similar features have been reported in spinal muscular atrophy (SMA), a motor neuron disease affecting infants. These findings, together with those reported in SMA, strongly suggest that reduction of minor spliceosomes has an important role in the pathomechanism underlying the selective degeneration of motor neurons characteristic of both ALS and SMA.

    DOI: 10.5692/clinicalneurol.54.1155

    Scopus

    PubMed

    researchmap

  • Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia Reviewed

    Masato Kanazawa, Mari Tada, Osamu Onodera, Hitoshi Takahashi, Masatoyo Nishizawa, Takayoshi Shimohata

    PARKINSONISM & RELATED DISORDERS   19 ( 12 )   1149 - 1151   2013.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCI LTD  

    Background: Patients who develop progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) develop cerebellar ataxia as the initial and principal symptom, may be misdiagnosed as having multiple system atrophy with predominant cerebellar features (MSA-C). Therefore, we investigated the clinical signs and symptoms between PSP-C and MSA-C early in their disease course.
    Methods: We reviewed the medical records of 15 consecutive patients with pathologically proven PSP-C (4) and MSA-C (11). We recorded the presence or absence of clinical features that developed within 2 years of disease onset.
    Results: The age at onset of PSP-C patients was older than that of MSA-C patients (p = 0.009). The frequencies of falls were higher in PSP-C patients than in MSA-C patients (p = 0.026). Additionally, the development of supranuclear vertical gaze palsy was higher in PSP-C patients than in MSA-C patients (p = 0.011), whereas the frequency of dysautonomia was lower in PSP-C patients than in MSA-C patients (p = 0.035).
    Conclusions: Older onset, early falls, and supranuclear vertical gaze palsy without dysautonomia may predict the diagnosis of PSP-C in patients with late-onset sporadic cerebellar ataxia. (C) 2013 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.parkreldis.2013.07.019

    Web of Science

    PubMed

    researchmap

  • ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19 Reviewed

    Yuji Takahashi, Yoko Fukuda, Jun Yoshimura, Atsushi Toyoda, Kari Kurppa, Hiroyoko Moritoyo, Veronique V. Belzil, Patrick A. Dion, Koichiro Higasa, Koichiro Doi, Hiroyuki Ishiura, Jun Mitsui, Hidetoshi Date, Budrul Ahsan, Takashi Matsukawa, Yaeko Ichikawa, Takashi Moritoyo, Mayumi Ikoma, Tsukasa Hashimoto, Fumiharu Kimura, Shigeo Murayama, Osamu Onodera, Masatoyo Nishizawa, Mari Yoshida, Naoki Atsuta, Gen Sobue, Jennifer A. Fifita, Kelly L. Williams, Ian P. Blair, Garth A. Nicholson, Paloma Gonzalez-Perez, Robert H. Brown, Masahiro Nomoto, Klaus Elenius, Guy A. Rouleau, Asao Fujiyama, Shinichi Morishita, Jun Goto, Shoji Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   93 ( 5 )   900 - 905   2013.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (PALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G&gt;A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C&gt;T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions.

    DOI: 10.1016/j.ajhg.2013.09.008

    Web of Science

    PubMed

    researchmap

  • Patient with insidious hypoactive delirium associated with pregabalin Reviewed

    Naomi Mezaki, Tomohiko Ishihara, Tetsutaro Ozawa, Ryoko Takeuchi, Osamu Onodera, Takayoshi Shimohata, Masatoyo Nishizawa

    Neurology and Clinical Neuroscience (Online Early View)   2013.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    researchmap

  • Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity Reviewed

    Fusako Usuki, Akio Yamashita, Tadafumi Shiraishi, Atsushi Shiga, Osamu Onodera, Itsuro Higuchi, Shigeo Ohno

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   110 ( 37 )   15037 - 15042   2013.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

    Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that eliminates aberrant mRNAs containing premature termination codons (PTCs). NMD inhibits the production of aberrant proteins that still retain, at least in part, wild-type function as well as dominant-negative peptides. Therefore, the selective inhibition of NMD has the potential to ameliorate NMD-exacerbated mutant phenotypes. However, we do not have sufficient knowledge of how to effectively suppress NMD with minimum cytotoxic effects. In this study, we aimed to identify NMD-related factors that can be targeted to efficiently inhibit NMD without causing significant cytotoxicity to restore the levels of truncated but partially functional proteins. We evaluated the knockdown of 15 NMD components in Ullrich congenital muscular dystrophy fibroblasts, which have a homozygous frameshift mutation causing a PTC in the collagen type VI a 2 gene. Of the 15 NMD factors tested, knockdown of SMG-8 produced the best effect for restoring defective mRNA and protein levels without affecting cell growth, cell-cycle progression, or endoplasmic reticulum stress. The efficacy of SMG-8 knockdown to improve the mutant phenotype was confirmed using another cell line, from a cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy patient who carries a PTC-containing mutation in HtrA serine peptidase 1. Our results suggest that SMG-8 is an appropriate target for inhibiting NMD to improve NMD-exacerbated mutant phenotypes. NMD inhibition by knockdown of SMG-8 may also be useful to induce synergy in combining the use of read-through drugs for patients with nonsense mutation-associated diseases.

    DOI: 10.1073/pnas.1300654110

    Web of Science

    PubMed

    researchmap

  • Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene Reviewed

    Hiroshi Shimizu, Yasuko Toyoshima, Atsushi Shiga, Akio Yokoseki, Keiko Arakawa, Yumi Sekine, Takayoshi Shimohata, Takeshi Ikeuchi, Masatoyo Nishizawa, Akiyoshi Kakita, Osamu Onodera, Hitoshi Takahashi

    Acta Neuropathologica   126 ( 3 )   453 - 459   2013.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met]
    [Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS. © 2013 Springer-Verlag Berlin Heidelberg.

    DOI: 10.1007/s00401-013-1150-5

    Scopus

    PubMed

    researchmap

  • Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy Reviewed

    Jun Mitsui, Takashi Matsukawa, Hiroyuki Ishiura, Yoko Fukuda, Yaeko Ichikawa, Hidetoshi Date, Budrul Ahsan, Yasuo Nakahara, Yoshio Momose, Yuji Takahashi, Atsushi Iwata, Jun Goto, Yorihiro Yamamoto, Makiko Komata, Katsuhiko Shirahige, Kenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hiroshi Takashima, Ryozo Kuwano, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Hiroyuki Soma, Ichiro Yabe, Hidenao Sasaki, Masashi Aoki, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Takamichi Hattori, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Tomoyoshi Kondo, Shigeo Murayama, Nobutaka Hattori, Mitsutoshi Yamamoto, Miho Murata, Wataru Satake, Tatsushi Toda, Alexandra Duerr, Alexis Brice, Alessandro Filla, Thomas Klockgether, Ullrich Wuellner, Garth Nicholson, Sid Gilman, Clifford W. Shults, Caroline M. Tanner, Walter A. Kukull, Virginia M. -Y. Lee, Eliezer Masliah, Phillip A. Low, Paola Sandroni, John Q. Trojanowski, Laurie Ozelius, Tatiana Foroud, Shoji Tsuji

    NEW ENGLAND JOURNAL OF MEDICINE   369 ( 3 )   233 - 244   2013.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MASSACHUSETTS MEDICAL SOC  

    Background
    Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system atrophy is widely considered to be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement of genetic components.
    Methods
    In combination with linkage analysis, we performed whole-genome sequencing of a sample obtained from a member of a multiplex family in whom multiple-system atrophy had been diagnosed on autopsy. We also performed mutational analysis of samples from members of five other multiplex families and from a Japanese series (363 patients and two sets of controls, one of 520 persons and one of 2383 persons), a European series (223 patients and 315 controls), and a North American series (172 patients and 294 controls). On the basis of these analyses, we used a yeast complementation assay and measured enzyme activity of parahydroxybenzoate-polyprenyl transferase. This enzyme is encoded by the gene COQ2 and is essential for the biosynthesis of coenzyme Q(10). Levels of coenzyme Q(10) in lymphoblastoid cells and brain tissue were measured on high-performance liquid chromatography.
    Results
    We identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2 in two multiplex families. Furthermore, we found that a common variant (V343A) and multiple rare variants in COQ2, all of which are functionally impaired, are associated with sporadic multiple-system atrophy. The V343A variant was exclusively observed in the Japanese population.
    Conclusions
    Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role of impaired COQ2 activities in the pathogenesis of this disease. (Funded by the Japan Society for the Promotion of Science and others.)
    Multiple-system atrophy is a rare neurodegenerative disease characterized by autonomic failure. Mutations affecting an enzyme essential for the synthesis of coenzyme Q10 confer susceptibility to the disease in some persons.

    DOI: 10.1056/NEJMoa1212115

    Web of Science

    researchmap

  • [Hereditary cerebral small-vessel disease]. Reviewed

    Nozaki H, Nishizawa M, Onodera O

    Nihon rinsho. Japanese journal of clinical medicine   71 ( 3 )   545 - 554   2013.3

  • Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS): Clinical Characteristics and Molecular Analyses of CSF-1R Reviewed

    Konno Takuya, Tada Masayoshi, Koyama Akihide, Tada Mari, Sugai Akihiro, Nozaki Hiroaki, Matsunaga Akiko, Harigaya Yasuo, Nishimiya Jin, Ishihara Kenji, Yoneda Makoto, Kakita Akiyoshi, Takahashi Hitoshi, Kawamura Mitsuru, Onodera Osamu, Nishizawa Masatoyo, Ikeuchi Takeshi

    NEUROLOGY   80   2013.2

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Early Clinical Features in Japanese Patients with Pathologically Proven Progressive Supranuclear Palsy with Cerebellar Ataxia Reviewed

    Masato Kanazawa, Takayoshi Shimohata, Mari Tada, Osamu Onodera, Hitoshi Takahashi, Masatoyo Nishizawa

    NEUROLOGY   80   2013.2

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1016/j.parkreldis.2013.07.019

    Web of Science

    researchmap

  • Molecular pathogenesis of ALS in TDP43 era Reviewed

    Osamu Onodera

    Clinical Neurology   53 ( 11 )   1077 - 1079   2013

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    To clarify the molecular pathogenesis of amyotrophic lateral sclerosis (ALS) associated with TAR-DNA binding protein 43?kDd (TDP-43), the quality and quantity of TDP-43 take a crucial role. Regarding to the quality of TDP-43, TDP-43 has been reported as an aggregate-prone protein. Especially the C-terminus of the TDP-43 tends to form aggregate and has prion-like domain. Interestingly the mutations in the genes, which produce proteins with prion-like domain, have been identified in several neurodegenerative disorders. These results suggest the existence of the common property in the causative proteins for neurodegenerative disorders. For the quantity of TDP-43, the adequate amount of TDP-43 is necessary for maintaining cell function and cell survival. The amount of TDP-43 is tightly regulated by TDP-43. However the mechanism for autoregulation has not been fully elucidated. For the function of TDP-43, TDP-43 locates at stress granule, GEM and associates with the large genes and introns. Thus the alteration of TDP-43 may affect the function of stress granule, GEM and RNA metabolism in several genes. Moreover a U12 type spliceosome, which is matured in GEM, is decreased in ALS. The investigation of whether these dysfunctions explain the selective pathology in ALS provides a new therapeutic strategy for ALS.

    DOI: 10.5692/clinicalneurol.53.1077

    Scopus

    PubMed

    researchmap

  • Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72 Reviewed

    Takuya Konno, Atsushi Shiga, Akira Tsujino, Akihiro Sugai, Taisuke Kato, Kazuaki Kanai, Akio Yokoseki, Hiroto Eguchi, Satoshi Kuwabara, Masatoyo Nishizawa, Hitoshi Takahashi, Osamu Onodera

    Journal of Neurology, Neurosurgery and Psychiatry   84 ( 4 )   398 - 401   2013

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMJ Publishing Group  

    Background A GGGGCC hexanucleotide repeat expansion in C9ORF72 occurs on a chromosome 9p21 locus that is linked with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in white populations. The diseases resulting from this expansion are referred to as 'c9FTD/ALS'. It has been suggested that c9FTD/ALS arose from a single founder. However, the existence of c9FTD/ALS in non-white populations has not been evaluated. Results We found two index familial ALS (FALS) patients with c9FTD/ALS in the Japanese population. The frequency of c9FTD/ALS was 3.4% (2/58 cases) in FALS. No patients with sporadic ALS (n=110) or control individuals (n=180) had the expansion. Neuropathological findings of an autopsy case were indistinguishable from those of white patients. Although the frequency of risk alleles identified in white subjects is low in Japanese, one patient had all 20 risk alleles and the other had all but one. The estimated haplotype indicated that the repeat expansion in these patients was located on the chromosome with the risk haplotype identified in white subjects. Conclusions C9ORF72 repeat expansions were present in a Japanese cohort of ALS patients, but they were rare. Intriguingly, Japanese patients appear to carry the same risk haplotype identified in white populations.

    DOI: 10.1136/jnnp-2012-302272

    Scopus

    PubMed

    researchmap

  • Alteration of POLDIP3 Splicing Associated with Loss of Function of TDP-43 in Tissues Affected with ALS Reviewed

    Atsushi Shiga, Tomohiko Ishihara, Akinori Miyashita, Misaki Kuwabara, Taisuke Kato, Norihiro Watanabe, Akie Yamahira, Chigusa Kondo, Akio Yokoseki, Masuhiro Takahashi, Ryozo Kuwano, Akiyoshi Kakita, Masatoyo Nishizawa, Hitoshi Takahashi, Osamu Onodera

    PLOS ONE   7 ( 8 )   e43120   2012.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PUBLIC LIBRARY SCIENCE  

    Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons. In the ALS motor neurons, TAR DNA-binding protein of 43 kDa (TDP-43) is dislocated from the nucleus to cytoplasm and forms inclusions, suggesting that loss of a nuclear function of TDP-43 may underlie the pathogenesis of ALS. TDP-43 functions in RNA metabolism include regulation of transcription, mRNA stability, and alternative splicing of pre-mRNA. However, a function of TDP-43 in tissue affected with ALS has not been elucidated. We sought to identify the molecular indicators reflecting on a TDP-43 function. Using exon array analysis, we observed a remarkable alteration of splicing in the polymerase delta interacting protein 3 (POLDIP3) as a result of the depletion of TDP-43 expression in two types of cultured cells. In the cells treated with TDP-43 siRNA, wild-type POLDIP3 (variant-1) decreased and POLDIP3 lacking exon 3 (variant-2) increased. The RNA binding ability of TDP-43 was necessary for inclusion of POLDIP3 exon 3. Moreover, we found an increment of POLDIP3 variant-2 mRNA in motor cortex, spinal cord and spinal motor neurons collected by laser capture microdissection with ALS. Our results suggest a loss of TDP-43 function in tissues affected with ALS, supporting the hypothesis that a loss of function of TDP-43 underlies the pathogenesis of ALS.

    DOI: 10.1371/journal.pone.0043120

    Web of Science

    PubMed

    researchmap

  • Primary lateral sclerosis: Upper-motor-predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration - immunohistochemical and biochemical analyses of TDP-43 Reviewed

    Takayuki Kosaka, Yong-Juan Fu, Atsushi Shiga, Haruka Ishidaira, Chun-Feng Tan, Takashi Tani, Ryoko Koike, Osamu Onodera, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    NEUROPATHOLOGY   32 ( 4 )   373 - 384   2012.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP-43 (pTDP-43) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP-43 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP-43 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP-43 immunoblotting revealed that fragments of similar to 25-kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the TDP-43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper-motor-predominant amyotrophic lateral sclerosis with FTLD-TDP.

    DOI: 10.1111/j.1440-1789.2011.01271.x

    Web of Science

    PubMed

    researchmap

  • Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene deletion, the mutation for spinocerebellar ataxia type 15, in Japan screened by gene dosage Reviewed

    Masato Obayashi, Kinya Ishikawa, Yuishin Izumi, Makoto Takahashi, Yusuke Niimi, Nozomu Sato, Osamu Onodera, Ryuji Kaji, Masatoyo Nishizawa, Hidehiro Mizusawa

    JOURNAL OF HUMAN GENETICS   57 ( 3 )   202 - 206   2012.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Spinocerebellar ataxia type 15 (SCA15) is an autosomal dominant neurodegenerative disorder clinically characterized by late-onset, slowly progressive pure cerebellar ataxia. This disease is caused by a heterozygous deletion of the inositol 1, 4, 5-triphosphate receptor type 1 (ITPR1) gene, suggesting that haploinsufficiency of the receptor function is the plausible disease mechanism. To clarify the prevalence of SCA15 in Japan, we designed four sets of probes and primers in different regions of ITPR1 and performed TaqMan PCR assay to search for gene deletions in 226 index SCA patients excluded for repeat expansion disorders. Deletion was found in only one patient, in whom gait ataxia started at 51 years of age and progressed to show cerebellar ataxia. This study demonstrates a simple but efficient method for screening ITPR1 deletion. We also conclude that ITPR1 gene deletions are much rare in Japan than in Europe, comprising only 0.3% in all SCAs in Japan. Journal of Human Genetics (2012) 57, 202-206; doi:10.1038/jhg.2012.5; published online 9 February 2012

    DOI: 10.1038/jhg.2012.5

    Web of Science

    PubMed

    researchmap

  • Co-occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis Reviewed

    K. Soma, Y. -J. Fu, K. Wakabayashi, O. Onodera, A. Kakita, H. Takahashi

    NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY   38 ( 1 )   54 - 60   2012.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    K. Soma, Y.-J. Fu, K. Wakabayashi, O. Onodera, A. Kakita and H. Takahashi (2012) Neuropathology and Applied Neurobiology38, 5460

    DOI: 10.1111/j.1365-2990.2011.01175.x

    Web of Science

    PubMed

    researchmap

  • What is ataxia? - Towards developing a new scale for ataxia Reviewed

    Osamu Onodera

    Clinical Neurology   52 ( 11 )   988 - 989   2012

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)  

    The molecular mechanism for ataxias has been elucidated in past 20 years. However, still it has not been developed a effective drug which prevents the disease progression or improves their symptom. One of the reasons for that is that the scales for ataxias, which we are using, are not suitable for clinical trial. The number of participant and the duration for a clinical trial is determined by the sensitivity and stability of scale to evaluate the efficacy the therapeutic methods. The available scale for ataxias needs more than 100 participants to evaluation the efficacy in more than 80% power. In addition, most of the scales for ataxias are a categorized scale, which is less sensitive and stable than a continuous scale. For success for clinical trial, we have to develop a new continuous scale for ataxias. In this symposium, we will learn the recent advance of physiological role of cerebellum and imagine a new continuous scale for evaluation for ataxias.

    DOI: 10.5692/clinicalneurol.52.988

    Scopus

    PubMed

    researchmap

  • Difference in MSA Phenotype Distribution Between Populations: Genetics or Environment? Reviewed

    Tetsutaro Ozawa, Tamas Revesz, Dominic Paviour, Andrew J. Lees, Niall Quinn, Mari Tada, Akiyoshi Kakita, Osamu Onodera, Koichi Wakabayashi, Hitoshi Takahashi, Masatoyo Nishizawa, Janice L. Holton

    JOURNAL OF PARKINSONS DISEASE   2 ( 1 )   7 - 18   2012

     More details

    Language:English   Publisher:IOS PRESS  

    The reasons for the differences in emphasis on striatonigral or olivopontocerebellar involvement in multiple system atrophy (MSA) remain to be determined. Semi-quantitative pathological analyses carried out in the United Kingdom and Japan demonstrated that olivopontocerebellar-predominant pathology was more frequent in Japanese MSA than British MSA. This observation provides evidence for a difference in phenotype distribution between British and Japanese patients with definite MSA. Studies of the natural history and epidemiology of MSA carried out in various populations have revealed that the relative prevalences of clinical subtypes of MSA probably differ among populations; the majority of MSA patients diagnosed in Europe have predominant parkinsonism (MSA-P), while the majority of MSA patients diagnosed in Asia have predominant cerebellar ataxia (MSA-C). Although potential drawbacks to the published frequencies of clinical subtypes and pathological subtypes should be considered because of selection biases, the difference demonstrated in pathological subtype is also consistent with the differences in clinical subtype of MSA demonstrated between Europe and Asia. Modest alterations in susceptibility factors may contribute to the difference in MSA phenotype distribution between populations. Synergistic interactions between genetic risk variants and environmental toxins responsible for parkinsonism or cerebellar dysfunction should therefore be explored. Further investigations are needed to determine the environmental, genetic, and epigenetic factors that account for the differences in clinicopathological phenotype of MSA among different populations.

    DOI: 10.3233/JPD-2012-11056

    Web of Science

    PubMed

    researchmap

  • [Dementia: progress in diagnosis and treatment; Topics, V. Recent topics; 4. Detection of novel dementia-related genes; 2) Dysregulation of TGF-beta family signaling and hereditary cerebral small vessel disease: insight into molecular pathogenesis of CARASIL]. Reviewed

    Nozaki, H., Nishizawa, M., Onodera, O.

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   100 ( 8 )   2207 - 2213   2011.8

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.2169/naika.100.2207

    Scopus

    PubMed

    researchmap

  • Neuroaxonal integrity evaluated by MR spectroscopy in a case of CARASIL Reviewed

    Yoshinori Nishimoto, Mamoru Shibata, Osamu Onodera, Norihiro Suzuki

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   82 ( 8 )   860 - 861   2011.8

     More details

    Language:English   Publisher:B M J PUBLISHING GROUP  

    DOI: 10.1136/jnnp.2010.240051

    Web of Science

    PubMed

    researchmap

  • Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family Reviewed

    Haruka Yamazaki, Hiroaki Nozaki, Osamu Onodera, Takayuki Michikawa, Masatoyo Nishizawa, Katsuhiko Mikoshiba

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   410 ( 4 )   754 - 758   2011.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Spinocerebellar ataxia type 15 (SCA15) is a group of human neurodegenerative disorders characterized by a slowly progressing pure cerebellar ataxia. The inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP(3)R1) is an intracellular IP3-induced Ca2+ release channel that was recently identified as a causative gene for SCA15. In most case studies, a heterozygous deletion of the IP(3)R1 gene was identified. However, one Japanese SCA15 family was found to have a Pro to Leu (P1059L) substitution in IP(3)R1. To investigate the effect of the P1059L mutation, we analyzed the channel properties of the mutant human IP(3)R1 by expressing it in an IP3R-deficient B lymphocyte cell line. The P1059L mutant was a functional Ca2+ release channel with a twofold higher IP3 binding affinity compared to wild-type IP(3)R1. The cooperative dependence of the Ca2+ release activity of the mutant on IP3 concentration was reduced, but both wild-type and mutant receptors produced similar B cell receptor-induced Ca2+ signals. These results demonstrate that the Ca2+ release properties of IP(3)R1 are largely unaffected by the P1059L mutation. (C) 2011 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2011.06.043

    Web of Science

    PubMed

    researchmap

  • What is cerebral small vessel disease? Reviewed

    Osamu Onodera

    Clinical Neurology   51 ( 6 )   399 - 405   2011.6

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    An accumulating amount of evidence suggests that the white matter hyperintensities on T2 weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease.

    DOI: 10.5692/clinicalneurol.51.399

    Scopus

    PubMed

    researchmap

  • Reduced bowel sounds in Parkinson&apos;s disease and multiple system atrophy patients Reviewed

    Tetsutaro Ozawa, Etsuji Saji, Ryuji Yajima, Osamu Onodera, Masatoyo Nishizawa

    CLINICAL AUTONOMIC RESEARCH   21 ( 3 )   181 - 184   2011.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER HEIDELBERG  

    Digital auscultation of bowel sounds was performed in newly diagnosed, drug-na &lt; ve patients with Parkinson&apos;s disease (PD) (n = 10), multiple system atrophy (MSA) (n = 12), progressive supranuclear palsy/corticobasal degeneration (PSP/CBD) (n = 7), and control subjects (n = 18). The number of bowel sounds per minute and the integrated time of bowel sounds were significantly lower in PD and MSA patients than in control subjects. Reduced bowel sounds may herald compromised gastrointestinal motility in patients with PD and MSA.

    DOI: 10.1007/s10286-010-0102-6

    Web of Science

    PubMed

    researchmap

  • A NOVEL MUTATION IN THE HTRA1 GENE CAUSES CARASIL WITHOUT ALOPECIA Reviewed

    Y. Nishimoto, M. Shibata, M. Nihonmatsu, H. Nozaki, A. Shiga, A. Shirata, K. Yamane, A. Kosakai, K. Takahashi, M. Nishizawa, O. Onodera, N. Suzuki

    NEUROLOGY   76 ( 15 )   1353 - 1355   2011.4

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1212/WNL.0b013e318215281d

    Web of Science

    PubMed

    researchmap

  • Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes Reviewed

    Takashi Matsukawa, Muriel Asheuer, Yuji Takahashi, Jun Goto, Yasuyuki Suzuki, Nobuyuki Shimozawa, Hiroki Takano, Osamu Onodera, Masatoyo Nishizawa, Patrick Aubourg, Shoji Tsuji

    NEUROGENETICS   12 ( 1 )   41 - 50   2011.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Adrenoleukodystrophy (ALD) is an X-linked disorder affecting primarily the white matter of the central nervous system occasionally accompanied by adrenal insufficiency. Despite the discovery of the causative gene, ABCD1, no clear genotype-phenotype correlations have been established. Association studies based on single nucleotide polymorphisms (SNPs) identified by comprehensive resequencing of genes related to ABCD1 may reveal genes modifying ALD phenotypes. We analyzed 40 Japanese patients with ALD. ABCD1 and ABCD2 were analyzed using a newly developed microarray-based resequencing system. ABCD3 and ABCD4 were analyzed by direct nucleotide sequence analysis. Replication studies were conducted on an independent French ALD cohort with extreme phenotypes. All the mutations of ABCD1 were identified, and there was no correlation between the genotypes and phenotypes of ALD. SNPs identified by the comprehensive resequencing of ABCD2, ABCD3, and ABCD4 were used for association studies. There were no significant associations between these SNPs and ALD phenotypes, except for the five SNPs of ABCD4, which are in complete disequilibrium in the Japanese population. These five SNPs were significantly less frequently represented in patients with adrenomyeloneuropathy (AMN) than in controls in the Japanese population (p = 0.0468), whereas there were no significant differences in patients with childhood cerebral ALD (CCALD). The replication study employing these five SNPs on an independent French ALD cohort, however, showed no significant associations with CCALD or pure AMN. This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes.

    DOI: 10.1007/s10048-010-0253-6

    Web of Science

    PubMed

    researchmap

  • TGF-β family signaling contributes to human cerebral small vessel disease Reviewed

    Osamu Onodera

    Clinical Neurology   51 ( 11 )   943 - 944   2011

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)  

    The discovery of the causative gene for hereditary cerebral small vessel disease (CARASIL: Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) opens a new avenue for exploring the pathogenesis of cerebral small vessel disease. The causative gene for CARASIL is HTRA1 (high-temperature requirement Al). HTRA1 is a serine protease and inhibits TGF-β signaling in their protease activitydependent manner. The CARASIL-associated mutant HTRA1s lost their protease activity and increase the TGF-β family signaling. However the precious molecular mechanism for inhibition of TGF-β signaling by HTRA1 has not been elucidated. We have found that HTRA1 aberrantly cleaved pro-TGF-β in an endoplasmic reticulum and the cleaved products were degraded by the endoplasmic reticulum-associated degradation pathway. The result reconfirms the importance of HTRA1 for TGF-β signaling. The study for Marfan syndrome, which is caused by the increasing TGF-β signaling in aortic artery, indicates that the angiotensin I receptor antagonist, a drug already in clinical use for hypertension, inhibits TGF-β signaling and ameliorates the disease progression in model mouse as well as patients with Marfan syndrome. In human brain, angiotensin I receptor antagonist also inhibits TGF-β signaling. Therefore angiotensin I receptor antagonist warrants investigation as a therapeutic strategy for patients with CARASIL.

    DOI: 10.5692/clinicalneurol.51.943

    Scopus

    PubMed

    researchmap

  • The phenotype spectrum of Japanese multiple system atrophy Reviewed

    T. Ozawa, M. Tada, A. Kakita, O. Onodera, M. Tada, T. Ishihara, T. Morita, T. Shimohata, K. Wakabayashi, H. Takahashi, M. Nishizawa

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   81 ( 11 )   1253 - 1255   2010.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:B M J PUBLISHING GROUP  

    Objective This study aimed to determine the spectrum of pathological involvement of the striatonigral (StrN) and olivopontocerebellar (OPC) systems in Japanese patients with multiple system atrophy (MSA). This study also aimed to compare the pathological spectrum of Japanese MSA patients with the previously reported results in British MSA patients.
    Methods A semiquantitative pathological analysis of 50 MSA patients&apos; brains that were referred to the Brain Research Institute, Niigata University, Japan, was performed. The severity of neuronal cell loss was determined as previously described by the study from the Queen Square Brain Bank (QSBB), UK.
    Results The mean neuronal cell loss score was significantly higher in the OPC area than in the basal ganglia sites examined, except the dorsolateral putamen. The relative prevalence of pathological phenotypes showed that 40% of cases had OPC-predominant pathology, 18% had StrN-predominant pathology and the remaining (42%) had equivalent StrN and OPC pathology. None of the MSA cases had coexistent Lewy bodies in the dorsal motor nucleus of the vagus and the substantia nigra.
    Conclusions In contrast to the previously reported results involving British patients&apos; brains from the QSBB (OPC-predominant pathology 17%, StrN-predominant pathology 34%, equivalent StrN and OPC pathology 49%), the results of the present study showed more pathological involvement of the OPC system than of the StrN system. The rarity of Lewy bodies may underlie the phenotypic expression of Japanese MSA. The present observations reflect the disequilibrium in the phenotype distribution between the two populations.

    DOI: 10.1136/jnnp.2009.182576

    Web of Science

    PubMed

    researchmap

  • [Clinical studies on neurological disorders conducted by research consortia]. Reviewed

    Onodera, O., Nakashima, K.

    Rinshō shinkeigaku = Clinical neurology   50 ( 11 )   925 - 925   2010.11

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • [FTLD/ALS as TDP-43 proteinopathies]. Reviewed

    Ishihara T, Ariizumi Y, Shiga A, Yokoseki A, Sato T, Toyoshima Y, Kakita A, Takahashi H, Nishizawa M, Onodera O

    Rinsho shinkeigaku = Clinical neurology   50 ( 11 )   1022 - 1024   2010.11

     More details

  • Involvement of Onuf&apos;s nucleus in Machado-Joseph disease: a morphometric and immunohistochemical study Reviewed

    Hiroshi Shimizu, Mitsunori Yamada, Yasuko Toyoshima, Takeshi Ikeuchi, Osamu Onodera, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   120 ( 4 )   439 - 448   2010.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG repeats in the MJD1 gene, in which lower urinary tract dysfunction is known to be the most commonly encountered autonomic failure. However, it remains unclear whether Onuf&apos;s nucleus (ON), which plays major roles in the micturition reflex and voluntary continence, degenerates during the disease process. In the present study, we conducted a morphometric and immunohistochemical study of ON, together with the lateral nuclear group (LNG) of the sacral anterior horns, in seven patients with MJD. When compared with controls, the number of lower motor neurons in both ON and LNG was significantly smaller in the MJD patients, the former being inversely correlated with the size of the expanded CAG repeats. Notably, MJD patients with a large CAG-repeat expansion showed an ON-predominant pattern of neuronal loss, while in the remaining patients, ON and LNG were affected to a similar degree, or rather an LNG-predominant pattern of neuronal loss was evident. Moreover, when adjusted for age, the degree of neuronal loss in both ON and LNG was significantly correlated with the extent of expansion of the CAG repeats. In MJD, the remaining lower motor neurons in ON often exhibited ataxin-3- or 1C2-immunoreactive (ir) neuronal intranuclear inclusions, while no pTDP-43-ir neuronal cytoplasmic inclusions were present in these neurons. In conclusion, the present findings strongly suggest that neuronal loss in ON, the degree of which is highly influenced by the extent of expansion of CAG repeats, is a consistent feature in MJD.

    DOI: 10.1007/s00401-010-0699-5

    Web of Science

    PubMed

    researchmap

  • Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huet anomaly Reviewed

    Nadezda Maksimova, Kenju Hara, Irina Nikolaeva, Tan Chun-Feng, Tomoaki Usui, Mineo Takagi, Yasushi Nishihira, Akinori Miyashita, Hiroshi Fujiwara, Tokuhide Oyama, Anna Nogovicina, Aitalina Sukhomyasova, Svetlana Potapova, Ryozo Kuwano, Hitoshi Takahashi, Masatoyo Nishizawa, Osamu Onodera

    JOURNAL OF MEDICAL GENETICS   47 ( 8 )   538 - 548   2010.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:B M J PUBLISHING GROUP  

    Background Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huet anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huet anomaly (SOPH) syndrome.
    Aims To identify a causative gene for SOPH syndrome.
    Methods Genomewide homozygosity mapping was conducted in 33 patients in 30 families.
    Results The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome.
    Conclusion These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huet anomaly.

    DOI: 10.1136/jmg.2009.074815

    Web of Science

    PubMed

    researchmap

  • Long-Term Disability and Prognosis in Dentatorubral-Pallidoluysian Atrophy: a Correlation with CAG Repeat Length Reviewed

    Arika Hasegawa, Takeshi Ikeuchi, Ryoko Koike, Nae Matsubara, Miyuki Tsuchiya, Hiroaki Nozaki, Atsushi Homma, Jiro Idezuka, Masatoyo Nishizawa, Osamu Onodera

    MOVEMENT DISORDERS   25 ( 11 )   1694 - 1700   2010.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion. Previous studies demonstrated that the onset of DRPLA is closely associated with CAG repeat length. However, the natural history of DRPLA has not yet been evaluated. We here retrospectively investigated the factors that determine the disease milestones and prognosis in 183 Japanese patients genetically diagnosed with DRPLA. We determined the age at onset, age at which each of the subsequent clinical manifestations appeared, age at becoming wheelchair-bound, and age at death. Kaplan-Meier analysis revealed that the patients with CAG repeats larger than the median length of 65 repeats developed each of the clinical features of DRPLA at a younger age than those with &lt;65 repeats. The patients became wheelchair-bound at a median age of 33 years (n = 61; range, 3-77 years) and died at a median age of 49 years (n = 23; range, 18-80 years). The ages at becoming wheelchair-bound and at death strongly correlated with the expanded CAG repeat length. Moreover, the patients with &gt;= 65 CAG repeats showed a more severe long-term disability and a poorer prognosis. In contrast, the rate of progression after the onset did not correlate with CAG repeat length. The CAG repeat length may have a considerable effect on not only the disease onset but also the disease milestones and prognosis in DRPLA patients. These effects of CAG repeat length may be relevant in designing future clinical therapeutic trials. (C) 2010 Movement Disorder Society

    DOI: 10.1002/mds.23167

    Web of Science

    PubMed

    researchmap

  • Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity Reviewed

    Yong-Juan Fu, Yasushi Nishihira, Shigetoshi Kuroda, Yasuko Toyoshima, Tomohiko Ishihara, Makoto Shinozaki, Akinori Miyashita, Yue-Shan Piao, Chun-Feng Tan, Takashi Tani, Ryoko Koike, Keisuke Iwanaga, Mitsuhiro Tsujihata, Osamu Onodera, Ryozo Kuwano, Masatoyo Nishizawa, Akiyoshi Kakita, Takeshi Ikeuchi, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   120 ( 1 )   21 - 32   2010.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.

    DOI: 10.1007/s00401-010-0649-2

    Web of Science

    PubMed

    researchmap

  • Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer&apos;s disease Reviewed

    Kensaku Kasuga, Takayoshi Tokutake, Atsushi Ishikawa, Tsuyoshi Uchiyama, Takahiko Tokuda, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   81 ( 6 )   608 - 610   2010.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:B M J PUBLISHING GROUP  

    Background The clinical diagnosis of dementia with Lewy bodies (DLB) is made on the basis of consensus criteria; however, the sensitivity of the criteria is relatively low. There are no generally accepted biomarkers to distinguish DLB from other dementias. Here the utility of quantification of a-synuclein, beta-amyloid42 (A beta 42) and tau in the CSF of patients with DLB, Alzheimer&apos;s disease (AD) and other dementias was examined.
    Methods 86 patients were divided into three age and sex matched groups: DLB (n=34), AD (n=31) and other dementias (n=21). Two patients with alpha-synuclein gene (SNCA) duplication were also examined. A beta and tau were quantified using an ELISA kit. A modified sandwich ELISA was developed which enables the sensitive quantification of CSF alpha-synuclein.
    Results Total and phosphorylated tau levels as well as A beta 40/42 and tau/A beta 42 ratios were significantly higher in AD patients than in patients with DLB (p&lt;0.01) and other dementias (p&lt;0.01). CSF alpha-synuclein levels in DLB patients were significantly lower than those in patients with AD (p&lt;0.05) and other dementias (p&lt;0.01). CSF alpha-synuclein level correlated with the A beta 42 level in DLB patients (p=0.01, r=0.43). Two patients with SNCA duplication exhibited relatively low levels of CSF alpha-synuclein.
    Conclusions The study suggests that reduced levels of CSF alpha-synuclein in DLB may reflect the accumulation of alpha-synuclein with Lewy pathology in the brain and that quantification of CSF alpha-synuclein helps in the differentiation of DLB from AD and other dementias in combination with A beta 42 and tau analysis.

    DOI: 10.1136/jnnp.2009.197483

    Web of Science

    PubMed

    researchmap

  • Molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy Reviewed

    Atsushi Shiga, Hiroaki Nozaki, Masatoyo Nishizawa, Osamu Onodera

    Brain and Nerve   62 ( 6 )   595 - 599   2010.6

     More details

    Language:Japanese  

    Ischemic cerebral small-vessel disease is a common disorder in the elderly. However, little is known about the molecular basis of ischemic cerebral small-vessel disease. We recently found that mutations in the HtrA serine peptidase 1 (HTRA1) gene cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). CARASIL is characterized by nonhypertensive cerebral small-vessel arteriopathy with alopecia and spondylosis. On neuropathologic examination, arteriosclerosis associated with intimal thickening and dense collagen fibers, loss of vascular smooth muscle cells, and hyaline degeneration of the media are observed in cerebral small arteries. These pathologic findings resemble those observed in patients with nonhereditary ischemic cerebral small-vessel disease. HTRA1 belongs to the HTRA protein family, the members of which have dual activities as chaperones and serine proteases. Studies have shown that members of the HTRA family repress transforming growth factor-β (TGF-β) family signaling. We found that CARASIL-associated mutant HTRA1s exhibited decreased protease activity and failed to repress TGF-β family signaling. Moreover, the amount of TGF-β1 was increased in the cerebral small arteries of CARASIL patients. In addition, the level of expression of ED-A fibronectin and versican, which is induced by TGF-β signaling, were accumulated in cerebral small arterial walls of a patient with CARASIL. Thus, we have concluded that the increased TGF-β signaling causes arteriopathy in CARASIL.

    Scopus

    PubMed

    researchmap

  • Alzheimer&apos;s disease: Report of two autopsy cases with a clinical diagnosis of corticobasal degeneration Reviewed

    Kenichi Okazaki, Yong-Juan Fu, Yasushi Nishihira, Minoru Endo, Takao Fukushima, Takeshi Ikeuchi, Kouichirou Okamoto, Osamu Onodera, Masatoyo Nishizawa, Hitoshi Takahashi

    NEUROPATHOLOGY   30 ( 2 )   140 - 148   2010.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    Alzheimer&apos;s disease (AD) is the most common cause of dementia in the elderly. Corticobasal degeneration (CBD) is a rare neurodegenerative disease affecting adults, being characterized clinically by a combination of extrapyramidal signs and focal cortical syndromes. In both diseases, tau deposits are a characteristic neuropathological feature. We report two new patients with autopsy-proven AD, in whom clinical diagnoses of CBD were made during life. The ages of the patients at onset were 52 and 67 years, and the disease durations were 9 and 15 years, respectively. At autopsy, both cases exhibited marked cortical atrophy with evident neuronal loss in the convex areas of the frontal and parietal lobes. Immunohistochemically, AT8-positive neurofibrillary tangles (NFTs) and A beta-positive senile plaques (SPs) were widespread and abundant in the cerebral cortex (Alzheimer pathology stage VI/C of Braak and Braak), leading us to the final pathological diagnosis of AD. No tau lesions suggestive of CBD were observed, and the deep gray matter areas, including the substantia nigra, were unremarkable (exceptionally, only mild neuronal loss was noted in the putamen in case 2). These findings further strengthen the idea that in AD, neurodegeneration with tau and A beta deposits may begin in the fronto-parietal neocortical areas, which are often preferentially affected in CBD, earlier than, or as early as the medial temporal lobe, and that extrapyramidal signs, such as rigidity and tremor, can occur in the absence of neuronal loss in the basal ganglia and substantia nigra.

    DOI: 10.1111/j.1440-1789.2009.01062.x

    Web of Science

    PubMed

    researchmap

  • Increased TGF-beta Signaling Underlies the Pathogenesis of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL) Reviewed

    Hiroaki Nozaki, Atushi Shiga, Hirotoshi Kawata, Kunimasa Arima, Kenju Hara, Toshio Fukutake, Akio Yokoseki, Akihide Koyama, Toshiaki Takahashi, Mari Ikeda, Akira Tanaka, Imaharu Nakano, Shu-ichi Ikeda, Tadashi Yamamoto, Takeshi Ikeuchi, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    NEUROLOGY   74 ( 9 )   A445 - A445   2010.3

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • The clinical and pathological spectrum of TDP-43 associated ALS Reviewed

    Osamu Onodera, AMo Yokoseki, Chun-Feng Tan, Tomohiko Ishihara, Yasushi Nishiira, Yasuko Toyoshima, AMyoshi Kakita, Masatoyo Nishizawa, Hitoshi Takahashi

    Clinical Neurology   50 ( 11 )   940 - 942   2010

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)  

    The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 KDa (TDP43) immunopositive cytoplasmic inclusions have been found in glia and neurons of ALS patients. The discovery of TDP-43 mutations in ALS patients indicates a direct role of TDP43 in ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore, the neuropathological findings for ALS-10, including TDP-43 immunopositive inclusions and Bunina bodies, are identical to those in sporadic ALS. Most of the mutations are located in the C-terminus of TDP43, which may function as a binding domain of heterogeneous nuclear ribonucleoprotein. Frontotemporal lobar degeneration: FTLD and FTLD/MND (motor neuron disease) also have TDP-43 immunopositive inclusions. These disorders have been named as TDP43 proteinopathy. However, patients with TDP-43 mutations rarely develop FTLD. Causative genes for familial FTLD and FTLD/MND are not linked to the TDP-43 gene. Thus, other factors may contribute to the TDP-43 pathology in these diseases. Further analysis is required to elucidate the molecular mechanism of ALS-10 and TDP-43 proteinopathy.

    DOI: 10.5692/clinicalneurol.50.940

    Scopus

    PubMed

    researchmap

  • Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia/Ataxia with Oculomotor Apraxia 1 Reviewed

    Masayoshi Tada, Akio Yokoseki, Tatsuya Sato, Takao Makifuchi, Osamu Onodera

    DISEASES OF DNA REPAIR   685   21 - 33   2010

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER-VERLAG BERLIN  

    DNA single-strand breaks (SSBs) are non-overlapping discontinuities in strands of a DNA duplex. Significant attention has been given on the DNA SSB repair (SSBR) system in neurons, because the impairment of the SSBR causes human neurodegenerative disorders, including early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also known as ataxia-oculomotor apraxia Type 1 (AOA1). EAOH/AOA1 is characterized by early-onset slowly progressive ataxia, ocular motor apraxia, peripheral neuropathy and hypoalbuminemia. Neuropathological examination reveals severe loss of Purkinje cells and moderate neuronal loss in the anterior horn and dorsal root ganglia. EAOH/AOA1 is caused by the mutation in the APTX gene encoding the aprataxin (APTX) protein. APTX interacts with X-ray repair cross-complementing group 1 protein, which is a scaffold protein in SSBR. In addition, APTX-defective cells show increased sensitivity to genotoxic agents, which result in SSBs. These results indicate an important role of APTX in SSBR. SSBs are usually accompanied by modified or damaged 5'- and 3'-ends at the break site. Because these modified or damaged ends are not suitable for DNA ligation, they need to be restored to conventional ends prior to subsequent repair processes. APTX restores the 5'-adenylate monophosphate, 3'-phosphates and 3'-phosphoglycolate ends. The loss of function of APTX results in the accumulation of SSBs, consequently leading to neuronal cell dysfunction and death.

    DOI: 10.1007/978-1-4419-6448-9_3

    Web of Science

    PubMed

    researchmap

  • The implications of TDP-43 mutations in pathogenesis of amyotrophic lateral sclerosis Reviewed

    Tomohiko Ishihara, Akio Yokoseki, Masatoyo Nishizawa, Hitoshi Takahashi, Osamu Onodera

    Brain and Nerve   61 ( 11 )   1301 - 1307   2009.11

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 kDa (TDP-43) -positive-cytoplasmic inclusions have been found in the glia and neurons of ALS patients. TDP-43 -positive inclusions have been reported in several neurodegenerative disorders other than ALS. Therefore it is not clear whether TDP-43 plays a primary role in the pathogenesis of ALS. The discovery of TDP-43 mutations in ALS patients indicates that TDP-43 plays a pivotal role in the pathogenesis of ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP-43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore, the neuropathological findings for ALS-10, including TDP-43 -positive inclusions and Bunina bodies, are identical to those in sporadic ALS
    these findings indicate that the study of ALS-10 may lead to a better understanding of sporadic ALS. Most of the mutations are located in the C-terminus of TDP-43, which may function as a binding domain for heterogeneous nuclear ribonucleoprotein. Biochemical analyses of TDP-43 in sporadic ALS patients indicate that the TDP-43 is truncated, and the C-terminus is phosphorylated forming insoluble inclusions in the neurons and glia. In certain ALS-10 cases, missense mutated TDP-43s tend to be truncated and form inclusions. The cytotoxicity of these mutated TDP-43s has also been reported
    however, these results are still controversial. Therefore, further analysis is required to elucidate the molecular mechanism underlying the development of ALS-10.

    Scopus

    PubMed

    researchmap

  • Selective occurrence of TDP-43-immunoreactive inclusions in the lower motor neurons in Machado-Joseph disease Reviewed

    Chun-Feng Tan, Mitsunori Yamada, Yasuko Toyoshima, Akio Yokoseki, Yukari Miki, Yasuhiro Hoshi, Hiroyuki Kaneko, Takeshi Ikeuchi, Osamu Onodera, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   118 ( 4 )   553 - 560   2009.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Pathological transactivation-responsive DNA-binding protein 43 (TDP-43) has been identified as a component of ubiquitinated inclusions in frontotemporal lobar degeneration with motor neuron disease, as well as in sporadic and some forms of familial amyotrophic lateral sclerosis. To clarify whether pathological TDP-43 is present in other neurodegenerative diseases involving the motor neuron system, we immunohistochemically examined the brain and spinal cord affected by two CAG repeat (polyglutamine) diseases, Machado-Joseph disease (MJD) and spinal and bulbar muscular atrophy (SBMA), using polyclonal antibody against TDP-43. In all the MJD cases, TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs), although few in number, were found only in the lower motor neurons in the brainstem and spinal cord. TDP-43-ir NCIs appeared as linear wisp-like, skein-like, or thick, somewhat rod-like bodies. These inclusions were also visualized with antibodies against phosphoserines 409 and 410 of TDP-43, and ubiquitin, but were not recognized by antibody against expanded polyglutamine stretches or ataxin-3. The ultrastructure of the TDP-43-ir NCIs was similar to that of the inclusions seen in sporadic ALS, consisting of bundles of parallel filaments. None of the SBMA cases showed abnormal TDP-43 immunoreactivity in any of the regions examined. Immunoblot analysis failed to recognize hyperphosphorylated TDP-43 at similar to 23 kDa in two MJD cases examined. However, the immunohistochemical findings strongly suggested that in MJD, in addition to the polyglutamine-dependent disease process, TDP-43-related pathogenesis is associated with degeneration and death of the lower motor neurons.

    DOI: 10.1007/s00401-009-0552-x

    Web of Science

    PubMed

    researchmap

  • Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease Reviewed

    K. Kasuga, T. Shimohata, A. Nishimura, A. Shiga, T. Mizuguchi, J. Tokunaga, T. Ohno, A. Miyashita, R. Kuwano, N. Matsumoto, O. Onodera, M. Nishizawa, T. Ikeuchi

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   80 ( 9 )   1050 - 1052   2009.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:B M J PUBLISHING GROUP  

    Background: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined.
    Methods: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients.
    Results: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls.
    Conclusions: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.

    DOI: 10.1136/jnnp.2008.161703

    Web of Science

    PubMed

    researchmap

  • Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation Reviewed

    Kensaku Kasuga, Tsukasa Ohno, Tomohiko Ishihara, Akinori Miyashita, Ryozo Kuwano, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi

    JOURNAL OF NEUROLOGY   256 ( 8 )   1351 - 1353   2009.8

     More details

    Language:English   Publisher:DR DIETRICH STEINKOPFF VERLAG  

    DOI: 10.1007/s00415-009-5096-4

    Web of Science

    PubMed

    researchmap

  • Novel GFAP Mutation in Patient with Adult-Onset Alexander Disease Presenting with Spastic Ataxia Reviewed

    Hiroyuki Kaneko, Masaki Hirose, Shinichi Katada, Toshiaki Takahashi, Satoshi Naruse, Miyuki Tsuchiya, Tomokatsu Yoshida, Masanori Nakagawa, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi

    MOVEMENT DISORDERS   24 ( 9 )   1393 - 1395   2009.7

     More details

    Language:English   Publisher:WILEY-LISS  

    DOI: 10.1002/mds.22556

    Web of Science

    PubMed

    researchmap

  • Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death Reviewed

    Mari Tada, Akiyoshi Kakita, Yasuko Toyoshima, Osamu Onodera, Tetsutaro Ozawa, Takashi Morita, Masatoyo Nishizawa, Hitoshi Takahashi

    BRAIN   132 ( Pt 7 )   1810 - 1819   2009.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by prominent autonomic failure with ataxia and/or parkinsonism. The leading cause of death in MSA is sudden death. We have shown that the early development of autonomic failure is an independent risk factor for sudden death. The depletion of sympathetic preganglionic neurons in the spinal intermediolateral cell column (IML) and its afferent medullary catecholaminergic and serotonergic neurons has been proposed to be partly responsible for autonomic failure in MSA. In this study, we investigated whether the depletion of neurons in any of these autonomic neuron groups contributes to sudden death in MSA. Out of 52 autopsy-proven patients with MSA, we selected 12 individuals who had died within 3.5 years after disease onset to define the accurate levels of slices and identify early neuropathological changes of autonomic nuclei in MSA. Four patients succumbed to sudden death and eight patients died through established causes. Serial 10 mu m sections were obtained from the 8th segment of the thoracic cord and the rostral medulla oblongata. Sections from the medulla oblongata were immunostained for thyrosine hydroxylase and tryptophan hydroxylase. The total cell number in the five sections was computed for comparison. Compared with the control, the MSA group showed a marked depletion of neurons in the IML (38.0 +/- 7.1 versus 75.2 +/- 7.6 cells, P &lt; 0.001), thyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla (VLM) (17.4 +/- 5.1 versus 72.8 +/- 13.6 cells, P &lt; 0.01) and tryptophan hydroxylase-immunoreactive neurons in the VLM (15.6 +/- 9.2 versus 60.8 +/- 17.0 cells, P &lt; 0.01), nucleus raphe obscurus (19.3 +/- 4.4 versus 75.3 +/- 8.6 cells, P &lt; 0.001), nucleus raphe pallidus (2.1 +/- 2.7 versus 9.0 +/- 3.4 cells, P &lt; 0.03), and arcuate nucleus (0.4 +/- 0.8 versus 2.3 +/- 1.5 cells, P &lt; 0.05). Moreover, in patients who succumbed to sudden death, when compared with patients who had established causes of death, we found a marked depletion of tryptophan hydroxylase-immunoreactive neurons in the VLM (7.3 +/- 3.5 versus 21.8 +/- 6.5 cells, P &lt; 0.02) and nucleus raphe obscurus (15.0 +/- 2.0 versus 22.5 +/- 2.1 cells, P &lt; 0.01). The results indicate that the spinal IML and medullary catecholaminergic and serotonergic systems are involved even in the early stages of MSA, and the dysfunction of the medullary serotonergic system regulating cardiovascular and respiratory systems could be responsible for sudden death in patients with MSA.

    DOI: 10.1093/brain/awp110

    Web of Science

    PubMed

    researchmap

  • Reliability of the Japanese version of the scale for the assessment and rating of ataxia (SARA) Reviewed

    Kazunori Sato, Ichiro Yabe, Hiroyuki Soma, Kenichi Yasui, Mizuki Ito, Takayoshi Shimohata, Osamu Onodera, Kenji Nakashima, Gen Sobue, Masatoyo Nishizawa, Hidenao Sasaki

    Brain and Nerve   61 ( 5 )   591 - 595   2009.5

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Background: The International Cooperative Ataxia Rating Scale (ICARS) is widely used as a scale for the assessment of the severity of cerebellar ataxia. However, this scale comprises several items
    thus, making the application of this scale is not sufficiently practical to perform daily assessment of ataxic patients. A new rating scale - Scale for the Assessment and Rating of Ataxia (SARA) - was shown to provide highly reliable assessments
    further, the scores on SARA correlated with the ICARS score and the Barthel index. After obtaining the permission, original SARA was translated into Japanese. Objective and Methods: To examine the reliability and internal consistency of the Japanese version of the SARA for the assessment of cerebellar ataxia in 66 patients with spinocerebellar degeneration. Results: Intraclass coefficients (ICC) were observed to be greater than 0.8 except in the case of the inter-rater "finger chase" and "fast alternating hand movement" tests. Conclusions: The Japanese version of SARA is highly reliable and very useful for the assessment of cerebellar ataxia on a daily basis.

    Scopus

    PubMed

    researchmap

  • Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice Reviewed

    Toshiya Sato, Masami Miura, Mitsunori Yamada, Takayuki Yoshida, Jonathan D. Wood, Ikuru Yazawa, Masao Masuda, Takeo Suzuki, Ryong-Moon Shin, Hau-Jie Yau, Fu-Chin Liu, Takayoshi Shimohata, Osamu Onodera, Christopher A. Ross, Motoya Katsuki, Hitoshi Takahashi, Masanobu Kano, Toshihiko Aosaki, Shoji Tsuji

    HUMAN MOLECULAR GENETICS   18 ( 4 )   723 - 736   2009.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    We herein provide a thorough description of new transgenic mouse models for dentatorubral-pallidoluysian atrophy (DRPLA) harboring a single copy of the full-length human mutant DRPLA gene with 76 and 129 CAG repeats. The Q129 mouse line was unexpectedly obtained by en masse expansion based on the somatic instability of 76 CAG repeats in vivo. The mRNA expression levels of both Q76 and Q129 transgenes were each 80% of that of the endogenous mouse gene, whereas only the Q129 mice exhibited devastating progressive neurological phenotypes similar to those of juvenile-onset DRPLA patients. Electrophysiological studies of the Q129 mice demonstrated age-dependent and region-specific presynaptic dysfunction in the globus pallidus and cerebellum. Progressive shrinkage of distal dendrites of Purkinje cells and decreased currents through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and gamma-aminobutyrate type A receptors in CA1 neurons were also observed. Neuropathological studies of the Q129 mice revealed progressive brain atrophy, but no obvious neuronal loss, associated with massive neuronal intranuclear accumulation (NIA) of mutant proteins with expanded polyglutamine stretches starting on postnatal day 4, whereas NIA in the Q76 mice appeared later with regional specificity to the vulnerable regions of DRPLA. Expression profile analyses demonstrated age-dependent down-regulation of genes, including those relevant to synaptic functions and CREB-dependent genes. These results suggest that neuronal dysfunction without neuronal death is the essential pathophysiologic process and that the age-dependent NIA is associated with nuclear dysfunction including transcriptional dysregulations. Thus, our Q129 mice should be highly valuable for investigating the mechanisms of disease pathogenesis and therapeutic interventions.

    DOI: 10.1093/hmg/ddn403

    Web of Science

    PubMed

    researchmap

  • A patient with anti-aquaporin 4 antibody who presented with recurrent hypersomnia, reduced orexin (hypocretin) level, and symmetrical hypothalamic lesions Reviewed

    Hiroaki Nozaki, Takayoshi Shimohata, Takashi Kanbayashi, Youhei Sagawa, Shin-ichi Katada, Masahisa Satoh, Osamu Onodera, Keiko Tanaka, Masatoyo Nishizawa

    SLEEP MEDICINE   10 ( 2 )   253 - 255   2009.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Recent studies have demonstrated that hypothalamic lesions associated with brain tumor, head trauma, and encephalopathy can cause symptomatic hypersomnia with a reduced orexin (hypocretin) level in the cerebrospinal fluid (CSF). Aquaporin 4 (AQP4) a member of the AQP superfamily, is strongly expressed in the hypothalamus in which orexin (hypocretin)-containing neurons are primarily concentrated. We report the case of a patient with a serum anti-AQP4 antibody who presented with recurrent hypersomnia, symmetrical hypothalamic lesions with long spinal cord lesions oil MRI, and a reduced CSF orexin (hypocretin) level, all of which were improved simultaneously by steroid therapy. Further studies Should be performed to determine the roles of anti-AQP4 antibody positivity in patients with hypersomnia associated with orexin (hypocretin) deficiency and hypothalamic lesions. (c) 2009 Published by Elsevier B.V.

    DOI: 10.1016/j.sleep.2007.11.022

    Web of Science

    PubMed

    researchmap

  • Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology Reviewed

    Nishihira, Y., Tan, C.-F., Hoshi, Y., Iwanaga, K., Yamada, M., Kawachi, I., Tsujihata, M., Hozumi, I., Morita, T., Onodera, O., Nishizawa, M., Kakita, A., Takahashi, H.

    Acta Neuropathologica   117 ( 1 )   45 - 53   2009.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Recently, sporadic amyotrophic lateral sclerosis (SALS), a fatal neurological disease, has been shown to be a multisystem proteinopathy of TDP-43 in which both neurons and glial cells in the central nervous system are widely affected. In general, the natural history of SALS is short (&lt;5 years). However, it is also known that a few patients may survive for 10 years or more, even without artificial respiratory support (ARS). In the present study using TDP-43 immunohistochemistry, we examined various regions of the nervous system in six patients with SALS of long duration (10-20 years) without ARS, in whom lower motor-predominant disease with Bunina bodies and ubiquitinated inclusions (UIs) in the affected lower motor neurons was confirmed. One case also showed UIs in the hippocampal dentate granule cells (UDG). In all cases, except one with UDG, the occurrence of TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs) was confined to a few regions in the spinal cord and brainstem, including the anterior horns. In one case with UDG, TDP-43-ir NCIs were also detected in the substantia nigra, and some regions of the cerebrum, including the hippocampal dentate gyrus (granule c

    DOI: 10.1007/s00401-008-0443-6

    Scopus

    PubMed

    researchmap

  • Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology Reviewed

    Yasushi Nishihira, Chun-Feng Tan, Yasuhiro Hoshi, Keisuke Iwanaga, Megumi Yamada, Izumi Kawachi, Mitsuhiro Tsujihata, Isao Hozumi, Takashi Morita, Osamu Onodera, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   117 ( 1 )   45 - 53   2009.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Recently, sporadic amyotrophic lateral sclerosis (SALS), a fatal neurological disease, has been shown to be a multisystem proteinopathy of TDP-43 in which both neurons and glial cells in the central nervous system are widely affected. In general, the natural history of SALS is short (&lt; 5 years). However, it is also known that a few patients may survive for 10 years or more, even without artificial respiratory support (ARS). In the present study using TDP-43 immunohistochemistry, we examined various regions of the nervous system in six patients with SALS of long duration (10-20 years) without ARS, in whom lower motor-predominant disease with Bunina bodies and ubiquitinated inclusions (UIs) in the affected lower motor neurons was confirmed. One case also showed UIs in the hippocampal dentate granule cells (UDG). In all cases, except one with UDG, the occurrence of TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs) was confined to a few regions in the spinal cord and brainstem, including the anterior horns. In one case with UDG, TDP-43-ir NCIs were also detected in the substantia nigra, and some regions of the cerebrum, including the hippocampal dentate gyrus (granule cells). The number of neurons displaying NCIs in each region was very small (1-3 per region, except the dentate gyrus). On the other hand, the occurrence of TDP-43-ir glial cytoplasmic inclusions (GCIs) was more widespread in the central nervous system, including the cerebral white matter. Again, however, the number of glial cells displaying GCIs in each region was very small (1-3 per region). In conclusion, compared to the usual form of SALS, TDP-43 pathology shown in SALS of long duration was apparently mild in degree and limited in distribution, corresponding to the relatively benign clinical courses observed. It is now apparent that SALS of long duration is actually part of a TDP-43 proteinopathy spectrum.

    DOI: 10.1007/s00401-008-0443-6

    Web of Science

    PubMed

    researchmap

  • Molecular mechanism for spinocerebellar ataxias Reviewed

    Osamu Onodera

    Clinical Neurology   49 ( 11 )   750 - 752   2009

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)  

    Recent advance of molecular biology reveals that quality control of intracellular environment takes an important role for maintaining the neuronal function. One is a quality control of protein and another is a quality control of nucleotide. Polyglutamine disease is a disease which caused by a failure of quality control of protein. Expanded polyglutamine repeats result in neurodegenerative disorders, but their cytotoxic structures remain to be elucidated. About the quality control of nucleotide in neuron, DNA single-strand breaks (SSBs) were continually produced by endogenous reactive oxygen species or exogenous genotoxic agents. These damaged ends posses damaged 3′-ends including 3′-phosphate, 3′-phosphoglycolate, or 3′-α, β-unsaturated aldehyde ends, and should be restored to 3′-hydroxyl ends for subsequent repair processes. We have demonstrated by in vitro assay that aprataxin, the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ ataxia with oculomotor apraxia type 1 (EAOH/AOA1), specifically removes 3′-phosphoglycolate and 3′-phosphate ends at DNA 3′-ends, but not 3′-α, β-unsaturated aldehyde ends. The findings indicate that aprataxin removes blocking molecules from 3′-ends, and that the accumulation of unrepaired SSBs with damaged 3′-ends underlies the pathogenesis of EAOH/AOA1. The findings will provide new insight into the mechanism underlying degeneration and DNA repair in neurons.

    DOI: 10.5692/clinicalneurol.49.750

    Scopus

    PubMed

    researchmap

  • Molecular mechanism for spinocerebellar ataxias Reviewed

    Osamu Onodera

    Clinical Neurology   49 ( 1 )   1 - 8   2009

     More details

    Language:Japanese   Publisher:Societas Neurologica Japonica  

    Recent advance of molecular biology reveals that quality control of intracellular environment takes an important role for maintaining the neuronal function. One is a quality control of protein and another is a quality control of nucleotide. Polyglutamine disease is a disease which caused by a failure of quality control of protein. Expanded polyglutamine repeats result in neurodegenerative disorders, but their cytotoxic structures remain to be elucidated. We have applied fluorescence resonance energy transfer analysis to clarify the cytotoxicity of soluble polyglutamine oligomers. By using this method we revealed that polyglutamine monomers assemble into oligomer in a parallel β-sheet or a head-to-tail cylindrical β-sheet manner. We distinguished oligomers from monomers and inclusion bodies in a single living cell. Survival assay of neuronally differentiated cells revealed that cells with soluble oligomers died faster than those with inclusion bodies or monomers. These results indicate that a formation of oligomers is an essential mechanism underlying neurodegeneration in polyglutamine-mediated disorders. About the quality control of nucleotide in neuron, DNA single-strand breaks were continually produced by endogenous reactive oxygen species or exogenous genotoxic agents. These damaged ends posses damaged 3′-ends including 3′-phosphate, 3′-phosphoglycolate, or 3′-α, β-unsaturated aldehyde ends, and should be restored to 3′-hydroxyl ends for subsequent repair processes. We have demonstrated by in vitro assay that aprataxin, the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomotor apraxia type 1 (EAOH/AOA1), specifically removes 3′-phosphoglycolate and 3′-phosphate ends at DNA 3′-ends, but not 3′-α, β-unsaturated aldehyde ends. The findings indicate that aprataxin removes blocking molecules from 3′-ends, and that the accumulation of unrepaired DNA single-strand breaks with damaged 3′-ends underlies the pathogenesis of EAOH/AOA1. The findings will provide new insight into the mechanism underlying degeneration and DNA repair in neurons. Taken together, these results indicate that the quality control of protein and nucleotide is crucial to understand the neurodegenerative disorder.

    DOI: 10.5692/clinicalneurol.49.1

    Scopus

    PubMed

    researchmap

  • Electroclinical features of epilepsy in patients with juvenile type dentatorubral-pallidoluysian atrophy Reviewed

    Kiyoshi Egawa, Yukitoshi Takahashi, Yuko Kubota, Hideki Kubota, Yushi Inoue, Takeki Fujiwara, Osamu Onodera

    EPILEPSIA   49 ( 12 )   2041 - 2049   2008.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    To clarify the electroclinical characteristics of epileptic seizures in patients with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA).
    Seventeen patients with juvenile type DRPLA confirmed by genetic analysis were studied retrospectively. The clinical records of all 17 patients and the ictal video electroencephalography (EEG) recordings from 12 of the 17 patients were reviewed.
    Electroclinical studies in 12 patients identified 11 habitual seizures in 6 patients as partial seizures on ictal video EEG recordings. Clinical manifestations composed mainly of versions of the head and loss of consciousness. These partial seizures were persistently recorded throughout the clinical course. Brief generalized seizures (atypical absence and myoclonic seizure) were observed in 6 of 12 patients at the early stage. In contrast, generalized tonic-clonic seizures (GTCS) were recorded in four advanced stage patients who were almost bedridden. Semiological studies in 17 patients showed that the prevalence of partial seizures was significantly higher in patients with younger epilepsy onset (below 10 years of age; chi(2) test, p &lt; 0.05) and that the age of epilepsy onset was significantly lower in patients with partial seizures than in those without partial seizures (Mann-Whitney U test, p = 0.02). However, the number of CAG repeats and age at clinical onset were not significantly different between two groups.
    Partial seizure is one of the common epileptic features in juvenile type DRPLA, especially in patients with younger epilepsy onset. Seizure types may be affected in an age-dependent manner and change evolutionally during progression of the clinical stage.

    DOI: 10.1111/j.1528-1167.2008.01701.x

    Web of Science

    PubMed

    researchmap

  • Cardiac sympathetic denervation in Parkinson's disease linked to SNCA duplication Reviewed

    Satoshi Orimo, Toshiki Uchihara, Ayako Nakamura, Fumiaki Mori, Takeshi Ikeuchi, Osamu Onodera, Masatoyo Nishizawa, Atsushi Ishikawa, Akiyoshi Kakita, Koichi Wakabayashi, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   116 ( 5 )   575 - 577   2008.11

     More details

    Language:English   Publisher:SPRINGER  

    DOI: 10.1007/s00401-008-0428-5

    Web of Science

    PubMed

    researchmap

  • Development of a high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis Reviewed

    Yuji Takahashi, Naomi Seki, Hiroyuki Ishiura, Jun Mitsui, Takashi Matsukawa, Atsushi Kishino, Osamu Onodera, Masashi Aoki, Nobuyuki Shimozawa, Shigeo Murayama, Yasuto Itoyama, Yasuyuki Suzuki, Gen Sobue, Masatoyo Nishizawa, Jun Goto, Shoji Tsuji

    ARCHIVES OF NEUROLOGY   65 ( 10 )   1326 - 1332   2008.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: Comprehensive resequencing of the causative and disease-related genes of neurodegenerative diseases is expected to enable (1) comprehensive mutational analysis of familial cases, (2) identification of sporadic cases with de novo or low-penetrant mutations, (3) identification of rare variants conferring disease susceptibility, and ultimately (4) better understanding of the molecular basis of these diseases.
    Objective: To develop a microarray-based high-throughput resequencing system for the causative and disease-related genes of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
    Design: Validation of the system was conducted in terms of the signal-to-noise ratio, accuracy, and throughput. Comprehensive gene analysis was applied for patients with ALS.
    Subjects: Ten patients with familial ALS, 35 patientswith sporadic ALS, and 238 controls.
    Results: The system detected point mutations with 100% accuracy and completed the resequencing of 270 kilobase pairs in 3 working days with greater than 99.9% accuracy of base calls, or the determination of base(s) at each position. Analysis of patients with familial ALS revealed 2 SOD1 mutations. Analysis of the 35 patients with sporadic ALS revealed a previously known SOD1 mutation, S134N, a novel putative pathogenic DCTN1 mutation, R997W, and 9 novel variants including 4 nonsynonymous heterozygous variants consisting of 2 in ALS2, 1 in ANG, and 1 in VEGF that were not found in the controls.
    Conclusion: The DNA microarray-based resequencing system is a powerful tool for high-throughput comprehensive analysis of causative and disease-related genes. It can be used to detect mutations in familial and sporadic cases and to identify numerous novel variants potentially associated with genetic risks.

    DOI: 10.1001/archneur.65.10.1326

    Web of Science

    PubMed

    researchmap

  • Marinesco-Sjogren syndrome with atrophy of the brain stem tegmentum and dysplastic cytoarchitecture in the cerebral cortex Reviewed

    Kenji Sakai, Mari Tada, Yosuke Yonemochi, Takashi Nakajima, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    NEUROPATHOLOGY   28 ( 5 )   541 - 546   2008.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Marinesco-Sjogren syndrome (MSS) is a progressive multisystem disease with autosomal recessive inheritance characterized by cataracts, mental retardation, and cerebellar ataxia. Recently, two causative genes for MSS, SIL1 and SARA2, have been identified. On the other hand, the histopathologic features of the CNS in this syndrome have not yet been clarified in detail. We report here the features of an autopsy case of MSS with progressive myopathy, in which atrophy of the cerebellum and brain stem tegmentum, retinal degeneration, and dysplastic cytoarchitecture in the cerebral cortex were evident. An elder brother of the patient showed quite similar symptoms, implying an autosomal recessive mode of inheritance. However, we detected no mutations in the available genes. This case appears to represent an unusual example of MSS manifesting widespread developmental anomaly and neuronal degeneration in the CNS.

    DOI: 10.1111/j.1440-1789.2008.00884.x

    Web of Science

    PubMed

    researchmap

  • Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population Reviewed

    M. Iijima, H. Koike, N. Hattori, A. Tamakoshi, M. Katsuno, F. Tanaka, M. Yamamoto, K. Arimura, G. Sobue, S. Yagihashi, T. Yamamura, S. Ikeda, M. Nakagawa, S. Kusunoki, K. Inoue, K. Hayasaka, K. Matsumura, Y. Ando, M. Baba, M. Nakazato, H. Yasuda, R. Kaji, O. Onodera, J. Kira, S. Kuwabara, K. Arimura, G. Sobue

    Journal of Neurology, Neurosurgery and Psychiatry   79 ( 9 )   1040 - 1043   2008.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Objective and methods: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates in Japan. Results: The prevalence rate per 100 000 was 1.61 in the total population
    2.01 in males and 1.23 in females. The age dependent prevalence rates were 0.23 in juveniles (&lt
    15 years old), 1.50 in young adults (15-55 years) and 2.31 in elderly adults (&gt
    55 years). The sex and age dependent prevalence rates were 0.22 in males and 0.24 in females in juveniles, 1.81 in males and 1.19 in females in young adults, and 3.12 in males and 1.64 in females in elderly adults. The annual incidence rate per 100 000 was 0.48 in the total population, 0.58 in males and 0.38 in females. The age dependent incidence rate was 0.06 in juveniles, 0.40 in young adults and 0.73 in elderly adults. The sex and age dependent incidence rate was 0.05 in males and 0.08 in females in juveniles, 0.50 in males and 0.30 in females in young adults, and 0.93 in males and 0.58 in females in elderly adults. Both the prevalence and incidence rates were very similar throughout the eight geographical areas studied, from the northern to the southern parts of Japan. Conclusions: The prevalence and incidence rates were similar to those reported in the Caucasian population. The pathogenic background is suggested to be common throughout the different races and geographic areas, while gender and age effects should be taken into account in the pathogenesis of CIDP.

    DOI: 10.1136/jnnp.2007.128132

    Scopus

    PubMed

    researchmap

  • Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families Reviewed

    K. Hara, A. Shiga, H. Nozaki, J. Mitsui, Y. Takahashi, H. Ishiguro, H. Yomono, H. Kurisaki, J. Goto, T. Ikeuchi, S. Tsuji, M. Nishizawa, O. Onodera

    NEUROLOGY   71 ( 8 )   547 - 551   2008.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Background: Spinocerebellar ataxia type 15 (SCA15) is a progressive neurodegenerative disorder characterized by pure cerebellar ataxia, very slow progression, and distinct cerebellar atrophy. The locus for SCA15 was first mapped to 3p24.2-3pter in an Australian family. We have subsequently mapped two Japanese families presenting with ataxia and postural tremor of the head, arm, or trunk to the SCA15 locus. Recently, partial deletions involving both the type 1 inositol 1,4,5-triphosphate receptor (ITPR1) and sulfatase modifying factor 1 (SUMF1) genes have been identified in Australian and British families with SCA15.
    Methods: We conducted fine haplotype analysis on the region including ITPR1. To identify the deletion, we conducted gene dosage analysis and array-based comparative genomic hybridization (aCGH) analysis. Gene expression analysis was performed using quantitative real-time reverse transcription PCR. Mutational analyses of ITPR1 and SUMF1 were also performed.
    Results: We have identified a 414-kb deletion including the entire ITPR1 and exon 1 of SUMF1 in patients in family A. The expression levels of ITPR1 and SUMF1 mRNAs of the patient were half those of the normal control. Furthermore, in family B, we have identified a C-to-T substitution at position 8581 of ITPR1, resulting in the amino acid substitution of leucine for proline at codon 1059, which is highly conserved among species.
    Conclusions: Our results strongly confirm that ITPR1 is the causative gene for SCA15 and suggest that we need to investigate the point mutation in ITPR1 in the patients with autosomal dominant cerebellar ataxia and tremor.

    DOI: 10.1212/01.wnl.0000311277.71046.a0

    Web of Science

    PubMed

    researchmap

  • Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions Reviewed

    Yasushi Nishihira, Chun-Feng Tan, Osamu Onodera, Yasuko Toyoshima, Mitsunori Yamada, Takashi Morita, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   116 ( 2 )   169 - 182   2008.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    A nuclear protein, 43-kDa TAR DNA-binding protein (TDP-43), was recently identified as a component of the ubiquitinated inclusions (UIs) in frontotemporal lobar degeneration (FTLD-U) and sporadic amyotrophic lateral sclerosis (SALS). In the present study using immunohistochemistry, we examined various regions of the nervous system in a series of 35 SALS cases using a polyclonal antibody against TDP-43. Seven of the 35 cases had disease durations of more than 10 years with artificial respiratory support (ARS; duration: 69-156 months). In all cases, TDP-43-immunoreactive (ir) neuronal and glial cytoplasmic inclusions (NCIs and GCIs) were found together in many regions, including the histologically affected lower motor neuron nuclei. Cluster analysis of the distribution pattern of TDP-43-ir NCIs for cases without ARS (n = 28) identified two types (type 1, n = 16; type 2, n = 12). Type 2 was distinguished from type 1 by the presence of TDP-43-ir NCIs in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra, and was significantly associated with dementia. Eleven of the 28 cases showed UIs in the hippocampal dentate granule cells, all of which had type-2 distribution pattern. Cases with ARS (n = 7) were also classified into the same types (type 1, n = 5; type 2, n = 2). Cases having type-1 distribution pattern (n = 21) showed no evident neuronal loss in most of the non-motor neuron nuclei where TDP-43-ir NCIs were present, whereas cases having type-2 distribution pattern (n = 14) often showed evident neuronal loss in the frontotemporal cortices, amygdaloid nuclei and substantia nigra. These findings indicate that SALS is a multisystem degenerative disease widely affecting both neurons and glial cells with a heterogeneous pattern of TDP-43-ir NCI distribution (SALS showing type-2 distribution pattern being closely linked to FTLD-U), and that long-term survival supported by a respirator has no apparent influence on the TDP-43 neuronal distribution pattern.

    DOI: 10.1007/s00401-008-0385-z

    Web of Science

    PubMed

    researchmap

  • Sporadic ataxias in Japan - a population-based epidemiological study Reviewed

    Shoji Tsuji, Osamu Onodera, Jun Goto, Masatoyo Nishizawa

    CEREBELLUM   7 ( 2 )   189 - 197   2008.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Sporadic spinocerebellar ataxias (SCAs) comprise heterogeneous diseases with poorly understood epidemiologies and etiologies. A population-based epidemiological analysis of sporadic ataxias in the Japanese population was described. The prevalence rate of SCAs in the Japanese population is estimated to be 18.5/100,000. Sporadic SCAs account for 67.2% of total SCAs including hereditary SCAs, with olivopontocerebellar atrophy (OPCA) being the most common form sporadic ataxia (64.7%). The natural history analysis conducted on the basis of International Cooperative Ataxia Rating Scale (ICARS) showed that only 33% of patients with OPCA were able to walk at least with one stick 4-5 years after the onset of OPCA, which is much less than that of patients with cortical cerebellar atrophy (CCA). Similarly, 43% of patients with OPCA were able to stand alone 4-5 years after the onset, while 76% of patients with CCA were able to stand alone at the same disease duration. A population-based epidemiological analysis should provide essential information on the natural history of SCAs.

    DOI: 10.1007/s12311-008-0028-x

    Web of Science

    PubMed

    researchmap

  • Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia Reviewed

    Takeshi Ikeuchi, Akiyoshi Kakita, Atsushi Shiga, Kensaku Kasuga, Hiryoyuki Kaneko, Chun-Feng Tan, Jiro Idezuka, Koichi Wakabayashi, Osamu Onodera, Takeshi Iwatsubo, Masatoyo Nishizawa, Hitoshi Takahashi, Atsushi Ishikawa

    ARCHIVES OF NEUROLOGY   65 ( 4 )   514 - 519   2008.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: Multiplication of the alpha-synuclein gene (SNCA) (OMIM 163890) has been identified as a causative mutation in hereditary Parkinson disease or dementia with Lewy bodies.
    Objective: To determine the genetic, biochemical, and neuropathologic characteristics of patients with autopsy-confirmed autosomal dominant Lewy body disease, with particular reference to the dosage effects of SNCA.
    Design: Four-generation family study.
    Setting: Academic research.
    Patients: We fractionated samples extracted from frozen brain tissues of 4 patients for biochemical characterization, followed by immunoblot analysis.
    Main Outcome Measures: We determined the dosages of SNCA and its surrounding genes by quantitative polymerase chain reaction analysis.
    Results: Quantitative polymerase chain reaction analysis revealed that 3 patients were heterozygous for SNCA duplication and 1 patient was homozygous for SNCA duplication. The homozygous patient showed earlier age at onset and earlier death, with more severe cognitive impairment than the heterozygous patients. Biochemical analysis revealed that phosphorylated alpha-synuclein accumulated in the sarkosyl-insoluble urea-extracted fraction of the brains of the patients.
    Conclusions: Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication. The homozygous patient demonstrated the most severe phenotype, suggesting that SNCA dosage has a considerable effect on disease phenotype even within a family. SNCA duplication results in the hyperaccumulation of phosphorylated alpha-synuclein in the brains of patients.

    DOI: 10.1001/archneur.65.4.514

    Web of Science

    PubMed

    researchmap

  • Mutational analysis in early-onset familial dementia in the Japanese population Reviewed

    Takeshi Ikeuchi, Hiroyuki Kaneko, Akinori Miyashita, Hiroaki Nozaki, Kensaku Kasuga, Tamao Tsukie, Miyuki Tsuchiya, Toru Imamura, Hideki Ishizu, Kenju Aoki, Atsushi Ishikawa, Osamu Onodera, Ryozo Kuwano, Masatoyo Nishizawa

    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS   26 ( 1 )   43 - 49   2008

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:KARGER  

    Background: Three major causative genes have been implicated as the cause of early-onset familial Alzheimer's disease (AD): the amyloid precursor protein gene (APP), presenilin-1 (PSEN1) and PSEN2. Although rare, a tau-related dementia with mutations in the microtubule-associated protein tau gene (MAPT) has been identified in patients showing clinical presentations similar to those of AD. Methods: We performed mutational analysis of APP, PSEN1, PSEN2, and MAPT in 10 Japanese families with early-onset dementia clinically diagnosed as probable Alzheimer's disease. Results: In 4 index patients, we identified 4 missense PSEN1 mutations, namely, L286V, G378E, L381V, and L392V. The mean age at onset in the patients with PSEN1 mutations was 39 years. In 2 families, we found the R406W mutation in MAPT. The mean age at onset of the patients carrying the R406W mutation was 52 years, and they presented with the peculiar AD-like phenotype without apparent behavioral or language problems. Conclusion: These observations suggest that although PSEN1 mutations are the most frequent cause, the MAPT R406W mutation is an important cause of early-onset familial dementia clinically diagnosed as AD. Differentiation of patients with the MAPT mutation from AD patients by genetic testing would be meaningful, considering that a different therapeutic approach should be applied. Copyright (c) 2008 S. Karger AG, Basel.

    DOI: 10.1159/000141483

    Web of Science

    PubMed

    researchmap

  • TDP-43 mutation in familial amyotrophic lateral sclerosis Reviewed

    Akio Yokoseki, Atsushi Shiga, Chun Feng Tan, Asako Tagawa, Hiroyuki Kaneko, Akihide Koyama, Hiroto Eguchi, Akira Tsujino, Takeshi Ikeuchi, Akiyoshi Kakita, Koichi Okamoto, Masatoyo Nishizawa, Hitoshi Takahashi, Osamu Onodera

    NEUROSCIENCE RESEARCH   61   S267 - S267   2008

     More details

    Language:English   Publisher:ELSEVIER IRELAND LTD  

    Web of Science

    researchmap

  • Contribution of APP duplication as a cause in a cohort of Japanese Alzheimer disease patients Reviewed

    Kensaku Kasuga, Atsushi Shiga, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi

    NEUROSCIENCE RESEARCH   61   S264 - S264   2008

     More details

    Language:English   Publisher:ELSEVIER IRELAND LTD  

    Web of Science

    researchmap

  • Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families Reviewed

    Hiroaki Nozaki, Kenju Hara, Atsushi Shiga, Jun Mitsui, Yuuji Takahashi, Hideaki Ishiguro, Harumi Shimono, Hiroshi Kurisaki, Jun Goto, Takeshi Ikeuchi, Shouji Tsuji, Masatoyo Nishizawa, Osamu Onodera

    NEUROSCIENCE RESEARCH   61   S206 - S206   2008

     More details

    Language:English   Publisher:ELSEVIER IRELAND LTD  

    Web of Science

    researchmap

  • The clinical-genealogic and molecular-genetic characteristics of oculopharyngeal muscular dystrophy in the Republic of Sakha (Yakutia) Reviewed

    N. R. Maksimova, I. A. Nikolaeva, M. N. Korotov, T. Ikeuchi, O. Onodera, M. Nishizawa, S. K. Stepanova, Kh. A. Kurtanov, A. L. Sukhomyasova, A. N. Nogovitcina, E. E. Gurinova, V. A. Stepanov, V. P. Puzyrev

    ZHURNAL NEVROLOGII I PSIKHIATRII IMENI S S KORSAKOVA   108 ( 6 )   52 - 60   2008

     More details

    Language:Russian   Publishing type:Research paper (scientific journal)   Publisher:IZDATELSTVO MEDITSINA  

    The clinical-genealogic and molecular-genetic investigation of oculopharyngeal muscular dystrophy (OPMD) in the Republic of Sakha (Yakutia) was performed. it was investigated 33 unrelated yakut families with 38 patients and 2 russian families with 2 patients and 59 their healthy relatives as well. The high clinical polymorphism of disease was found in patients with OPMD. The mutation in exon 1 of the PABPN1 gene resulting in the expansion of GCG-repeats up to 10 is revealed. Using direct sequencing of the PABPN1 gene in 17 families (16 yakut, 1 russian), we identified a type of this mutation as an insertion of 4 GCG-repeats. Frequency of OPMD in the yakut population is 1:11 680 that is 10-20 times higher comparing to european populations. This is a first report on the patients with OPMD from the Republic of Sakha with diagnosis confirmed by molecular-genetic analysis.

    Web of Science

    PubMed

    researchmap

  • Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia Reviewed

    N. Maksimova, K. Hara, A. Miyashia, I. Nikolaeva, A. Shiga, A. Nogovicina, A. Sukhomyasova, V. Argunov, A. Shvedova, T. Ikeuchi, M. Nishizawa, R. Kuwano, O. Onodera

    JOURNAL OF MEDICAL GENETICS   44 ( 12 )   772 - 778   2007.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMJ PUBLISHING GROUP  

    Background: In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified.
    Methods: Because Yakuts are considered as a population isolate and the disease is rare in other populations, genomewide homozygosity mapping was performed using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut.
    Results: All families shared an identical haplotype in the same region as the identical loci responsible for 3-M and gloomy face syndromes and a novel homozygous 4582insT mutation in Cullin 7 (CUL7) was found, which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 ( Q1553X). Yakut patients with short stature syndrome have unique features such as a high frequency of neonatal respiratory distress and few bone abnormalities, whereas the clinical features of the other Yakut patients were similar to those of 3-M syndrome. Furthermore, abnormal vascularisation was present in the fetal placenta and an abnormal development of cartilage tissue in the bronchus of a fetus with CUL7 mutation.
    Conclusion: These findings may provide a new understanding of the clinical diversity and pathogenesis of short stature syndrome with CUL7 mutation.

    DOI: 10.1136/jmg.2007.051979

    Web of Science

    PubMed

    researchmap

  • Enhanced accumulation of phosphorylated alpha-synuclein and elevated beta-amyloid 42/40 ratio caused by expression of the presenilin-1 Delta T440 mutant associated with familial Lewy body disease and variant Alzheimer's disease Reviewed

    Hiroyuki Kaneko, Akiyoshi Kakita, Kensaku Kasuga, Hiroaki Nozaki, Atsushi Ishikawa, Akinori Miyashita, Ryozo Kuwano, Genta Ito, Takeshi Iwatsubo, Hitoshi Takahashi, Masatoyo Nishizawa, Osamu Onodera, Sangram S. Sisodia, Takeshi Ikeuchi

    JOURNAL OF NEUROSCIENCE   27 ( 48 )   13092 - 13097   2007.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    Mutations in the PSEN1 gene encoding presenilin 1 ( PS1) are linked to a vast majority of pedigrees with early- onset, autosomal dominant forms of familial Alzheimer's disease ( FAD). Lewy body ( LB) pathology is frequently found in the brains of FAD patients harboring PSEN1 mutations. We recently reported on a novel PS1 mutation with the deletion of threonine at codon 440 (Delta T440) in a familial case diagnosed as having the neocortical type of dementia with LBs ( DLB) and variant AD. In this report, we investigated the possible involvement of PS1 Delta T440 mutation in aberrant alpha-synuclein accumulation. We established cell lines that stably express either wild- type ( WT) PS1 or the FAD- linked PS1 H163R, E280A, Delta E9, and PS1 Delta T440 mutants and now demonstrate that the expression of the PS1 Delta T440 mutant led to a marked elevation in the ratio of beta-amyloid (A beta) 42/40 peptides in a conditioned medium. More importantly, we report here that the levels of phosphorylated alpha-synuclein increase in neuronal and non- neuronal cells expressing the PS1 Delta T440 mutant compared with cells that express WT PS1 or the PS1 H163R and E280A variants that are not associated with LB pathology. This finding is consistent with our demonstration of elevated levels of phosphorylated alpha-synuclein in the detergent-resistant fraction prepared from a patient's brain with PS1 Delta T440 mutation. These observations raise the intriguing suggestion that the mechanism( s) by which the PS1 Delta T440 mutant causes DLB and variant AD are by enhancing the phosphorylation of alpha-synuclein and the ratio of A beta(42/40) peptides, respectively, in the brain.

    DOI: 10.1523/JNEUROSCI.4244-07.2007

    Web of Science

    PubMed

    researchmap

  • Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3 q23.3. Reviewed International journal

    Takayoshi Shimohata, Kenju Hara, Kazuhiro Sanpei, Jin-ichi Nunomura, Tetsuya Maeda, Izumi Kawachi, Masato Kanazawa, Kensaku Kasuga, Akinori Miyashita, Ryozo Kuwano, Koichi Hirota, Shoji Tsuji, Osamu Onodera, Masatoyo Nishizawa, Yoshiaki Honma

    Brain : a journal of neurology   130 ( Pt 9 )   2302 - 9   2007.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Autosomal dominant choreas are genetically heterogeneous disorders including Huntington disease (HD), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), dentatorubro-pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17) and benign hereditary chorea (BHC). We identified two Japanese families with adult-onset benign chorea without dementia inherited in an autosomal dominant pattern. All affected individuals presented slowly progressive choreic movements in their upper and lower extremities, trunk and head with an age of onset ranging from 40 to 66 (average 54.3), which were markedly improved by haloperidol. The affected individuals also developed reduced muscle tones in their extremities. The findings obtained in the brain CT or MRI studies of nine affected individuals were normal. These clinical features resemble those of the so-called 'senile chorea'. HD, HDL1, HDL2, DRPLA, SCA17 and BHC caused by mutations in the TITF-1 gene were excluded by mutational and linkage analyses. A genome-wide linkage analysis revealed linkage to chromosome 8q21.3-q23.3 with a maximum cumulative two-point log of the odds (LOD) score of 4.74 at D8S1784 (theta = 0.00). Haplotype analysis of both the families defined the candidate region as 21.5 Mb interval flanked by M9267 and D8S1139. We named this adult-onset dominant inherited chorea 'benign hereditary chorea type 2 (BHC2)'.

    DOI: 10.1093/brain/awm036

    Web of Science

    PubMed

    researchmap

  • Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3 q23.3. Reviewed International journal

    Takayoshi Shimohata, Kenju Hara, Kazuhiro Sanpei, Jin-ichi Nunomura, Tetsuya Maeda, Izumi Kawachi, Masato Kanazawa, Kensaku Kasuga, Akinori Miyashita, Ryozo Kuwano, Koichi Hirota, Shoji Tsuji, Osamu Onodera, Masatoyo Nishizawa, Yoshiaki Honma

    Brain : a journal of neurology   130 ( Pt 9 )   2302 - 9   2007.9

     More details

    Language:English  

    Autosomal dominant choreas are genetically heterogeneous disorders including Huntington disease (HD), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), dentatorubro-pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17) and benign hereditary chorea (BHC). We identified two Japanese families with adult-onset benign chorea without dementia inherited in an autosomal dominant pattern. All affected individuals presented slowly progressive choreic movements in their upper and lower extremities, trunk and head with an age of onset ranging from 40 to 66 (average 54.3), which were markedly improved by haloperidol. The affected individuals also developed reduced muscle tones in their extremities. The findings obtained in the brain CT or MRI studies of nine affected individuals were normal. These clinical features resemble those of the so-called 'senile chorea'. HD, HDL1, HDL2, DRPLA, SCA17 and BHC caused by mutations in the TITF-1 gene were excluded by mutational and linkage analyses. A genome-wide linkage analysis revealed linkage to chromosome 8q21.3-q23.3 with a maximum cumulative two-point log of the odds (LOD) score of 4.74 at D8S1784 (theta = 0.00). Haplotype analysis of both the families defined the candidate region as 21.5 Mb interval flanked by M9267 and D8S1139. We named this adult-onset dominant inherited chorea 'benign hereditary chorea type 2 (BHC2)'.

    DOI: 10.1093/brain/awm036

    PubMed

    researchmap

  • Generation of intracellular domain of insulin receptor tyrosine kinase by gamma-secretase Reviewed

    K. Kasuga, H. Kaneko, M. Nishizawa, O. Onodera, T. Ikeuchi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   360 ( 1 )   90 - 96   2007.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The proteolytic cleavage of a precursor protein into alpha- and beta-subunits by furin is required to form functional insulin receptor (IR). In this study, we examined if IR undergoes the additional presenilin (PS)/gamma- secretase-dependent processing. In cells treated with gamma-secretase inhibitors or expressing the dominant-negative PS1 variant led to the accumulation of an endogenous IR C-terminal fragment. In the presence of proteasome inhibitors, we detected a PS/gamma-secretase cleavage product of the IR, termed the IR intracellular domain (ICD). Cellular fractionation and confocal microscopy analyses showed that the IR-ICD is predominantly detected in the nucleus. These data indicate that IR is a tyrosine kinase receptor, which undergoes PS/gamma-secretase-dependent processing. We also show that the auto-phosphorylation levels of the IR P-subunit upon insulin stimulation were decreased by the inactivation of PS/gamma-secretase, raising the possibility that the PS/gamma-secretase proteolysis of IR may play a modulatory role in insulin signaling. (c) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2007.06.022

    Web of Science

    PubMed

    researchmap

  • Sacsin-related ataxia with neither retinal hypermyelination nor spasticity Reviewed

    Kenju Hara, Junsuke Shimbo, Hiroaki Nozaki, Koki Kiku-Awa, Osamu Onodera, Masatoyo Nishizawa

    MOVEMENT DISORDERS   22 ( 9 )   1362 - 1363   2007.7

     More details

    Language:English   Publisher:WILEY-LISS  

    DOI: 10.1002/mds.21557

    Web of Science

    PubMed

    researchmap

  • Daytime hypoxemia, sleep-disordered breathing, and laryngopharyngeal findings in multiple system atrophy Reviewed

    Takayoshi Shimohata, Hideo Shinoda, Hideaki Nakayama, Tetsutaro Ozawa, Kenshi Terajima, Hirohisa Yoshizawa, Yoko Matsuzawa, Osamu Onodera, Satoshi Naruse, Keiko Tanaka, Sugata Takahashi, Fumitake Gejyo, Masatoyo Nishizawa

    ARCHIVES OF NEUROLOGY   64 ( 6 )   856 - 861   2007.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne- Stokes respiration; or an impaired hypoxemic ventilatory response.
    Objective: To investigate the mechanism of sleep-disordered breathing in multiple system atrophy ( MSA).
    Design: We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia.
    Results: A decrease in arterial oxygen pressure and an increase in alveolar- arterial oxygen gradient significantly correlated with disease duration ( P=. 045 and.046, respectively). Polysomnography demonstrated CheyneStokes respiration in 3 ( 15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 ( 14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 ( 45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 ( 55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid.
    Conclusions: We observed daytime hypoxemia with an increased alveolar- arterial oxygen gradient, CheyneStokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.

    DOI: 10.1001/archneur.64.6.856

    Web of Science

    PubMed

    researchmap

  • TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation Reviewed

    Chun-Feng Tan, Hiroto Eguchi, Asako Tagawa, Osamu Onodera, Takuya Iwasaki, Akira Tsujino, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   113 ( 5 )   535 - 542   2007.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Recently, 43-kDa TAR DNA-binding protein (TDP-43) was identified as a component of ubiquitinated inclusions (UIs) in sporadic amyotrophic lateral sclerosis (SALS). To clarify whether TDP-43 immunoreactivity is present in neuronal inclusions in familial ALS (FALS), we examined immunohistochemically the brains and spinal cords from four cases of FALS, two with Cu/Zn superoxide dismutase (SOD1) gene mutation and two without, together with three cases of SALS and three control subjects, using two antibodies, one polyclonal and one monoclonal, against TDP-43. Neuropathologically, the SOD1-related FALS cases were characterized by Lewy body-like hyaline inclusions (LBHIs) in the lower motor neurons. On the other hand, the SOD1-unrelated FALS cases showed degeneration restricted to the upper and lower motor neuron systems, with Bunina bodies (BBs) and UIs in the lower motor neurons, being indistinguishable from SALS. No cytoplasmic TDP-43 immunoreactivity was observed in the control subjects or SOD1-related FALS cases; LBHIs were ubiquitinated, but negative for TDP-43. UIs observed in the SALS and SOD1-unrelated FALS cases were clearly positive for TDP-43. BBs were negative for this protein. Interestingly, in these SALS and FALS cases, glial cells were also found to have cytoplasmic TDP-43-positive inclusions. These findings indicate that the histological and molecular pathology of SALS can occur as a phenotype of FALS without SOD1 mutation.

    DOI: 10.1007/s00401-007-0206-9

    Web of Science

    PubMed

    researchmap

  • New mutation in the non-gigantic exon of SACS in Japanese siblings Reviewed

    Yuhei Takado, Kenju Hara, Takayoshi Shimohata, Susumu Tokiguchi, Osamu Onodera, Masatoyo Nishizawa

    MOVEMENT DISORDERS   22 ( 5 )   748 - 749   2007.4

     More details

    Language:English   Publisher:WILEY-LISS  

    DOI: 10.1002/mds.21365

    Web of Science

    PubMed

    researchmap

  • Multiplex families with multiple system atrophy Reviewed

    Kenju Hara, Yoshio Momose, Susumu Tokiguchi, Mitsuteru Shimohata, Kenshi Terajima, Osamu Onodera, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Motoyuki Hirasawa, Yoshikuni Mizuno, Katsuhisa Ogata, Jun Goto, Ichiro Kanazawa, Masatoyo Nishizawa, Shoji Tsuji

    ARCHIVES OF NEUROLOGY   64 ( 4 )   545 - 551   2007.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance.
    Objective: To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects.
    Design: Clinical and genetic study. Setting: Four departments of neurology in Japan.
    Patients: Eight patients in 4 families with parkinsonism, cerebellar ataxia, and autonomic failure with age at onset ranging from 58 to 72 years. Two siblings in each family were affected with these conditions.
    Main Outcome Measures: Clinical evaluation was performed according to criteria by Gilman et al. Trinucleotide repeat expansion in the responsible genes for the spinocerebellar ataxia (SCA) series and for dentatorubral-pallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the alpha-synuclein gene was performed.
    Results: Consanguineous marriage was observed in 1 of 4 families. Among 8 patients, 1 had definite MSA, 5 had probable MSA, and 2 had possible MSA. The most frequent phenotype was MSA with predominant parkinsonism, observed in 5 patients. Six patients showed pontine atrophy with cross sign or slitlike signal change at the posterolateral putaminal margin or both on brain magnetic resonance imaging. Possibilities of hereditary ataxias, including SCA1 (ataxin 1, ATXN1), SCA2 (ATXN2), Machado-Joseph disease/SCA3 (ATXN1), SCA6 (ATXN1), SCA7 (ATXN7), SCA12 (protein phosphatase 2, regulatory subunit B, beta isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the alpha-synuclein gene were found.
    Conclusions: Findings in these multiplex families suggest the presence of familial MSA with autosomal recessive inheritance and a genetic predisposition to MSA. Molecular genetic approaches focusing on familial MSA are expected to provide clues to the pathogenesis of MSA.

    DOI: 10.1001/archneur.64.4.545

    Web of Science

    PubMed

    researchmap

  • Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population Reviewed

    Hiroaki Nozaki, Takeshi Ikeuchi, Akio Kawakami, Akio Kimura, Reiji Koide, Miyuki Tsuchiya, Yuusaku Nakmura, Tatsuro Mutoh, Hiroko Yamamoto, Naoki Nakao, Ko Sahashi, Masatoyo Nishizawa, Osamu Onodera

    MOVEMENT DISORDERS   22 ( 6 )   857 - 862   2007.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Autosomal dominant spinocerebellar ataxias (AD-SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, a single nucleotide substitution in the 5'-untranstated region of the puratrophin-1 gene was found to be associated with one type of AD-SCA linked to chromosome 16q (16q-SCA). To obtain further insight into the contribution of the C-to-T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16q-SCA, we analyzed 686 families with 719 individuals diagnosed with progressive ataxia. We found C-to-T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals. The mean age at onset in the patients with 16q-SCA was 59.1 (range, 46-77). Ataxia is the most common initial symptom. The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes, involuntary movements, and reduced vibration sense. We also examined the frequency of the AD-SCA subtype, considering the effects of age at onset. In the 686 AD-SCA families, SCA6 and Machado-Joseph disease/ SCA3 are frequent subtypes, followed by dentatorubral-pallidoluysian atrophy and 16q-SCA. 16q-SCA is not a rare subtype of Japanese AD-SCA, particularly in patients with ages at onset over 60. (c) 2007 Movement Disorder Society.

    DOI: 10.1002/mds.21443

    Web of Science

    PubMed

    researchmap

  • Botulinum toxin A injections improve apraxia of eyelid opening without overt blepharospasm associated with neurodegenerative diseases Reviewed

    Masato Kanazawa, Takayoshi Shimohata, Masahisa Sato, Osamu Onodera, Keiko Tanaka, Masatoyo Nishizawa

    MOVEMENT DISORDERS   22 ( 4 )   597 - 598   2007.3

     More details

    Language:English   Publisher:WILEY-LISS  

    DOI: 10.1002/mds.21367

    Web of Science

    PubMed

    researchmap

  • New locus for benign hereditary chorea with adult-onset maps to chromosome 8q22.2-q23.3 Reviewed

    Kenju Hara, Takayoshi Shimohata, Sanpei Kazuhiro, Jin-ichi Nunomura, Izumi Kawachi, Masato Kanazawa, Kensaku Kasuga, Akinori Miyashita, Ryozo Kuwano, Koichi Hirota, Shoji Tsuji, Osamu Onodera, Masatoyo Nishizawa, Yoshiaki Honma

    NEUROLOGY   68 ( 12 )   A326 - A327   2007.3

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Familial amyotrophic lateral sclerosis: a SOD1-unrelated Japanese family of bulbar type with Bunina bodies and ubiquitin-positive skein-like inclusions in lower motor neurons Reviewed

    Asako Tagawa, Chun-Feng Tan, Koki Kikugawa, Masayuki Fukase, Ryoichi Nakano, Osamu Onodera, Masatoyo Nishizawa, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   113 ( 2 )   205 - 211   2007.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    We describe a new family with adult onset amyotrophic lateral sclerosis (FALS), in which the disease was characterized clinically by relatively rapid progression of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed in one patient showed no mutations. Autopsy of another patient demonstrated degenerative changes restricted to the upper and lower motor neuron systems; no evident changes were observed in the posterior column, Clarke&apos;s column or spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive skein-like inclusions in the lower motor neuron was of considerable interest. Cases of FALS with such pathological features are quite rare in the literature. Identification of the gene responsible for the disease is desirable in order to shed further light on the molecular pathology of not only familial, but also sporadic, ALS.

    DOI: 10.1007/s00401-006-0151-z

    Web of Science

    PubMed

    researchmap

  • Novel mutation in EIF2B gene in a case of adult-onset leukoencephalopathy with vanishing white matter Reviewed

    Masaru Matsui, Kotaro Mizutani, Hiroaki Ohtake, Yukio Miki, Koichi Ishizu, Hidenao Fukuyama, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa, Yoshihiro Takayama, Hiroshi Shibasaki

    EUROPEAN NEUROLOGY   57 ( 1 )   57 - 58   2007

     More details

    Language:English   Publisher:KARGER  

    DOI: 10.1159/000097120

    Web of Science

    PubMed

    researchmap

  • Spinocerebellar ataxia with ocular motor apraxia and DNA repair Reviewed

    Osamu Onodera

    NEUROPATHOLOGY   26 ( 4 )   361 - 367   2006.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BLACKWELL PUBLISHING  

    At least four disorders, ataxia telangiectasia (AT), an ataxia-telangiectasia-like disorder, early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1), and ataxia with oculomotor apraxia type 2, are accompanied by ocular motor apraxia (OMA), which is an impairment of saccadic eye movement initiation. The characteristic pathological findings of EAOH/AOA1 and AT are a severe loss of Purkinje cells, severe myelin pallor of the posterior columns, and moderate neuronal loss in the dorsal root ganglia and anterior horn. Purkinje cells stimulate the fastigial nucleus and suppress omnipause neurons to initiate saccadic eye movement. The selective loss of Purkinje cells might cause OMA and disturb the cancellation of the vestibulo-ocular reflex. These disorders have the following common clinical features: ataxia, involuntary movements, and peripheral neuronopathy. In addition, the causative genes for these disorders are associated with the DNA/RNA quality control system. The impairment of DNA/RNA integrity results in selective neuronal loss in these recessive-inherited ataxias.

    DOI: 10.1111/j.1440-1789.2006.00741.x

    Web of Science

    PubMed

    researchmap

  • Long-terms therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis Reviewed

    Masayoshi Tada, Takayoshi Shimohata, Mari Tada, Mutsuo Oyake, Shuichi Igarashi, Osamu Onodera, Satoshi Naruse, Keiko Tanaka, Shoji Tsuji, Masatoyo Nishizawa

    JOURNAL OF THE NEUROLOGICAL SCIENCES   247 ( 1 )   17 - 20   2006.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Objective: To elucidate the long-term therapeutic efficacy and safety of low-dose FK506 (tacrolimus) in patients with myasthenia gravis (MG).
    Patients and methods: We treated nine patients with MG (all women: age range: 35-83years (mean: 51.1 years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients) with FK506 for more than 24months (observation period: 24-46months). All the patients had undergone extended thymectomy before FK506 treatment; two patients (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We evaluated total Quantitative MG (Q-MG) score, anti-acetylcholine receptor (AM) antibody titer in the blood, interleukin 2 (IL-2) production in peripheral blood mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and adverse effects of FK506.
    Results: A reduction in steroid dosage of 50 50% without worsening of the symptoms was observed 1 year after FK506 administration in three out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0-39 points) at 6months and l year after FK506 administration improved by 3 points or more in six (66.7%) and seven (77.8 %) out of nine patients, respectively. The efficacy of FK506 was maintained for more than 2years. Although adverse effects were observed in three patients (33.3 %), these were not serious.
    Conclusions: Our study indicates that low-dose FK506 treatment may be efficacious not only in controlling intractable myasthenic symptoms, but also in reducing steroid dosage, and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a maximum of 3 years. (c) 2006 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jns.2006.03.010

    Web of Science

    PubMed

    researchmap

  • New HSN2 mutation in Japanese patient with hereditary sensory and autonomic neuropathy type 2 Reviewed

    M Takagi, T Ozawa, K Hara, S Naruse, T Ishihara, J Shimbo, S Igarashi, K Tanaka, O Onodera, M Nishizawa

    NEUROLOGY   66 ( 8 )   1251 - 1252   2006.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Hereditary sensory and autonomic neuropathies (HSANs) are heterogenous disorders characterized by a loss of pain sensation and autonomic abnormalities caused by peripheral nerve degeneration. (1) HSANs are clinically classified into five entities based on the inheritance pattern and clinical presentations. Mutations in at least six genes, SPTLC1, RAB7, HSN2, IKBKAP, TRKA, and NGFB, are known to be causative for the clinical varieties of HSANs. (1)
    HSAN2 is clinically characterized by autosomal recessive inheritance, the onset of symptoms in infancy or early childhood, the occurrence of paronychia, whitlows, ulcers of distal extremities, unrecognized fractures of the foot and hand, anhidrosis, sensory loss that affects all modalities of sensations in the lower and upper limbs, the absence or diminution of tendon reflexes, the absence of sensory nerve action potentials (SNAPs), and the virtual absence of myelinated fibers with a decreased number of unmyelinated fibers in sural nerves. (1)
    To date, seven truncated mutations of the HSN2 gene have been identified among HSAN2 families from Quebec, Newfoundland, and Nova Scotia in Canada, and Lebanon, Italy, and Austria. (2-5) Here, we describe a new truncated mutation in the HSN2 gene of a Japanese patient with HSAN2.

    DOI: 10.1212/01.wnl.0000208415.90685.cd

    Web of Science

    PubMed

    researchmap

  • Oral cyclophosphamide therapy for multifocal fibrosclerosis with hypertrophic intracranial pachymeningitis Reviewed

    Masayoshi Tada, Osamu Onodera, Kenju Hara, Keiko Tanaka, Hitoshi Takahashi, Shoji Tsuji, Masatoyo Nishizawa

    Clinical Neurology   46 ( 2 )   128 - 133   2006.2

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A 54-year-old man was admitted to our hospital because of a headache, dry cough, low grade fever and hearing loss sustained for 6 months. Physical and neurological examinations revealed bilateral conjunctival hyperemia, fine crackles in the lower lungs, cutaneous scars, horizontal gaze evoked nystagmus, bilateral moderate sensorineural deafness and mild hyperreflexia. Hypertrophic intracranial pachymeningitis (HIP) accompanied by episcleritis, pulmonary fibrosis, subcutaneous fibrosis of the trunk and upper limbs, bilateral chronic otitis media and sinusitis of the paranasal cavities were observed. Histopathological investigation of biopsied tissues from the dura matter, lung, skin and nasal mucosa showed marked fibrosis with lymphocyte and plasma cell infiltrations. The diagnosis of multifocal fibrosclerosis (MF) was made
    this is a rare syndrome of unknown etiology characterized by fibrosis involving multiple organ systems. Although steroid pulse therapy and cyclophosphamide (CP) pulse therapy was not effective in his illnesses, the combination therapy of corticosteroid and oral CP was dramatically effective. We concluded that HIP can be a manifestation of MF, and additional oral CP should be considered as a treatment for steroid-resistant MF with HIP.

    Scopus

    PubMed

    researchmap

  • Churg-Strauss syndrome and the leukotriene receptor antagonist pranlukast Reviewed

    J Shimbo, O Onodera, K Tanaka, S Tsuji

    CLINICAL RHEUMATOLOGY   24 ( 6 )   661 - 662   2005.12

     More details

    Language:English   Publisher:SPRINGER  

    The authors studied eight cases of Churg-Strauss syndrome (CSS) associated with the use of pranlukast, a common cysteinyl leukotriene receptor antagonist (LTRA) in Japan. The patients who received pranlukast showed significantly increased peripheral blood eosinophil count, neurological disability scores, and poor responses to corticosteroid in comparison with those patients not receiving pranlukast. We suggest that preceding administration of pranlukast aggravates clinical presentations of CSS.

    DOI: 10.1007/s10067-004-1035-z

    Web of Science

    PubMed

    researchmap

  • DNA repair and neurodegeneration Reviewed

    Osamu Onodera

    Clinical Neurology   45 ( 11 )   979 - 981   2005.11

     More details

    Language:Japanese   Publishing type:Research paper (international conference proceedings)  

    Early onset ataxia with hypoalbuminemia (AOA1/EAOH) patients begin with ocular motor apraxia and cerebellar ataxia in childhood, and then develop axonal peripheral neuropathy and hypoalbuminemia. We and others identified 'aprataxin (APTX) ' as the causative gene for AOA1/EAOH. APTX binds to XRCC1, which is the scaffold protein for BER machinery, and has a HIT-motif, which is supposed to have hydrolase activity on nucleotide. These properties suggest that APTX acts on DNA during single strand DNA break. The 3′-termini of single strand DNA break must be hydroxylated to allow DNA polymerase or ligase to repair
    however, ordinary the 3′-termini is modified by phosphate or others. These unsuitable ends have to be removed to repair. To investigate whether the APTX works on DNA and remove the unsuitable 3′-end, we incubated recombinant human APTX with variable oligonucleotide. We show that APTX has bidirectional exonuclease activity and 3′-phosphatase activity. These results indicate that APTX might modify the phosphorylated 3′-end in a single strand DNA break. To date several diseases have been identified as caused by an impairment of quality control system of DNA/ RNA. The impairment of quality control system of DNA/RNA is a new pathway for neuronal degeneration.

    Scopus

    PubMed

    researchmap

  • Selective silencing of a mutant transthyretin allele by small interfering RNAs Reviewed

    T Kurosawa, S Igarashi, M Nishizawa, O Onodera

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   337 ( 3 )   1012 - 1018   2005.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis caused by dominantly acting missense mutations in the gene encoding transthyretin (TTR). The most common mutant TTR is of the Va130Met type, which results from a point mutation. Because the major constituent of amyloid fibrils is mutant TTR, agents that selectively suppress mutant TTR expression could be powerful therapeutic tools. This study has been performed to evaluate the use of small interfering RNAs (siRNAs) for the selective silencing of mutant Va130Met TTR in cell culture systems. We have identified an siRNA that specifically inhibits mutant, but not wild-type, TTR expression even in cells expressing both alleles. Thus, this siRNA-based approach may have potential for the gene therapy of FAR (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2005.09.142

    Web of Science

    PubMed

    researchmap

  • Natural history of X-linked adrenoleukodystrophy in Japan Reviewed

    Y Suzuki, Y Takemoto, N Shimozawa, T Imanaka, S Kato, H Furuya, M Kaga, K Kato, N Hashimoto, O Onodera, S Tsuji

    BRAIN & DEVELOPMENT   27 ( 5 )   353 - 357   2005.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    The natural history of X-linked adrenoleukodystrophy (ALD) was investigated, using a nation-wide retrospective study based on a questionnaire survey. The data on 145 patients, including 46 patients with the childhood cerebral form, 39 with adrenomyeloneuropathy (AMN), 33 with the adult cerebral form, 14 with the adolescent form and 13 with the olivo-ponto-cerebellar (OPC) form, were analyzed. Initial symptoms of the childhood cerebral form were intellectual (n=16) and visual (n = 11) disturbances, whereas those of AMN were gait (n = 37) and sensory (n = 3) disturbances; the adult cerebral form, psychic (n= 19) and gait (n = 11)disturbances; the adolescent form, visual n = 5) and gait (n = 4) disturbances; and the OPC form, gait (n = 9) disturbance. Patients with onset under the age of 8 years progressed more rapidly than those over 8 years old. Visual, hearing, gait and swallowing disturbances progressed more slowly in the older group. About half of AMN patients showed cerebral involvement about 10 years after onset. Patients with the OPC form also showed a similar progression. A Kaplan-Meier plot clarified the characteristic pattern of progression of neurological symptoms in each phenotype. These finding will improve the understanding of the natural history of X-linked ALD and will provide a basis for the evaluation of specific treatment for X-linked ALD. (c) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.braindev.2004.09.008

    Web of Science

    PubMed

    researchmap

  • Age associated axonal features in HNPP with 17p11.2 deletion in Japan Reviewed

    H Koike, M Hirayama, M Yamamoto, H Ito, N Hattori, F Umehara, K Arimura, S Ikeda, Y Ando, M Nakazato, R Kaji, K Hayasaka, M Nakagawa, S Sakoda, K Matsumura, O Onodera, M Baba, H Yasuda, T Saito, J Kira, K Nakashima, N Oka, G Sobue

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   76 ( 8 )   1109 - 1114   2005.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:B M J PUBLISHING GROUP  

    Objective: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy ( HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities.
    Methods: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls.
    Results: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination.
    Conclusions: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.

    DOI: 10.1136/jnnp.2004.048140

    Web of Science

    PubMed

    researchmap

  • A late-onset case of oculopharyngeal muscular dystrophy carrying a (GCG) 8 repeat expansion in the PAPBN1 gene Reviewed

    Takayoshi Tokutake, Takeshi Ikeuchi, Keiko Tanaka, Osamu Onodera, Masatoyo Nishizawa

    Clinical Neurology   45 ( 6 )   437 - 440   2005.6

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report a sporadic case of a female patient with oculopharyngeal muscular dystrophy (OPMD). Her father died at age 86 and mother at age 74. There was no familial occurrence of the disease. The patient initially developed a nasal voice at age 66. Neurological examinations on admission at age 72 revealed bilateral ptosis, a limitation of ocular movement without diplopia, dysphagia, and proximal muscle weakness. Serum creatine kinase level was slightly increased. Biopsied muscle specimens showed variation in fiber size as well as the occasional presence of rimmed vacuoles. On the basis of these clinical and laboratory findings, we suspected a diagnosis of OPMD, although a family history was absent. To confirm the diagnosis of OPMD, we performed a gene analysis for poly A binding protein, nuclear 1 (PABPN1
    PABP2), which revealed a mild expansion of GCG repeat (8 repeats) as a heterozygous state. Clinical features of the patient were consistent with those in a previous literature reporting that patients carrying (GCG) 8 repeat as a heterozygous state show a relatively late onset and a mild phenotype. The case of this patient emphasizes the importance of the PABPN1 gene analysis for patients showing muscular weakness involving oculopharyngeal and proximal limb muscles even when a familial occurrence of the disease is not apparent.

    Scopus

    PubMed

    researchmap

  • Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP Reviewed

    M Iijima, M Yamamoto, M Hirayama, F Tanaka, M Katsuno, K Mori, H Koike, N Hattori, K Arimura, M Nakagawa, H Yoshikawa, K Hayasaka, O Onodera, M Baba, H Yasuda, T Saito, M Nakazato, K Nakashima, J Kira, R Kaji, N Oka, G Sobue

    NEUROLOGY   64 ( 8 )   1471 - 1475   2005.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy ( CIDP), the authors conducted a multicenter study on 312 patients with CIDP ( 199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle action potential were pronounced in nonresponders of IVIg. Male gender, longer disease duration, and slow progression of symptoms were also associated with IVIg unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP.

    DOI: 10.1212/01.WNL.0000158680.89323.F8

    Web of Science

    PubMed

    researchmap

  • A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease Reviewed

    A Ishikawa, YS Piao, A Miyashita, R Kuwano, O Onodera, H Ohtake, M Suzuki, M Nishizawa, H Takahashi

    ANNALS OF NEUROLOGY   57 ( 3 )   429 - 434   2005.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    We report early-onset parkinsonism and dementia of 18 years' duration in a 52-year-old man whose grandfather and father had suffered from a similar neurological disease. In this patient, we found neuronal loss in various brain regions including the substantia nigra and cerebral cortex, Lewy bodies, cotton wool plaques, corticospinal tract degeneration, cerebral amyloid angiopathy, and a novel three-base pair deletion in exon 12 of the presenilin-1 (PSEN1) gene. We considered that the mutant PSEN1 might play an important role in the pathogenetic process of both aggregation of a-synuclein into Lewy bodies and deposition of beta-amyloid into cotton wool plaques.

    DOI: 10.1002/ana.20393

    Web of Science

    PubMed

    researchmap

  • Sacsin-related autosomal recessive ataxia without prominent retinal myelinated fibers in Japan Reviewed

    K Hara, O Onodera, M Endo, H Kondo, H Shiota, K Miki, N Tanimoto, T Kimura, M Nishizawa

    MOVEMENT DISORDERS   20 ( 3 )   380 - 382   2005.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has been described in the Quebec region and in Tunisia. We report on two Japanese siblings with a new homozygous mutation (6543 del A) of the SACS gene. Compared with previously reported ARSACS patients, both of these patients had a unique phenotype characterized by dementia, ophthalmoplegia, and the absence of prominent retinal myelinated fibers. (c) 2004 Movement Disorder Society.

    DOI: 10.1002/mds.20315

    Web of Science

    PubMed

    researchmap

  • A pedigree of Charcot-Marie-Tooth disease type 4F (Periaxin mutation) Reviewed

    Mitsuteru Shimohata, Kiyoshi Hirahara, Shuichi Igarashi, Kenju Hara, Kazuki Kijima, Osamu Onodera, Keiko Tanaka, Masatoyo Nishizawa, Shoji Tsuji, Kiyoshi Hayasaka

    Clinical Neurology   45 ( 3 )   221 - 225   2005.3

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report a 51-year-old man genetically diagnosed as Charcot-Marie-Tooth disease type 4F. The patient was the first child of healthy, consanguineous parents. He had two sisters and one of them showed similar but milder symptoms. He had gait disturbance since childhood. Then he noticed muscle weakness of his hands at the age of early forties, and more difficulties in gait at the age of late forties. On examination at age 51, he showed absence of all deep tendon reflexes, weakness of the hand and distal leg muscles, pes cavus and decreased sensitivity to touch and vibration in the lower extremities. Electrophysiological studies of the median nerve showed delayed motor nerve conduction velocity and undetectable sensory nerve action potentials. The histology of his sural nerve revealed moderate loss of large myelinated fibers and the diameters of residual fibers shifted to small shown as size-frequency histogram. Many fibers are thinly myelinated and some of the Schwann cells looked as wrapping around the myelinate fibers with their processes. On gene analyses, we identified an Arg 1070 Stop homozygous mutation in the Periaxin, known to be a causative gene for CMT type 4F. Based on these observations, we emphasized that broad genetic analyses are necessary for diagnosis of CMT disease, including so far unidentified mutations among the Japanese populations.

    Scopus

    PubMed

    researchmap

  • Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation Reviewed

    T Takahashi, K Nozaki, S Tsuji, M Nishizawa, O Onodera

    NEUROREPORT   16 ( 3 )   295 - 299   2005.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Transcriptional dysregulation, particularly cAMP-responsive-element-mediated transcriptional repression, has been implicated in expanded polyglutamine diseases. However, it has not been clarified whether this transcriptional repression is a cause or result of neurodegeneration. Furthermore, the association between aggregates of expanded polyglutamine stretches and transcriptional repression is not clear. We established isogenic cell lines with polyglutamine stretches, which also expressed d2EGFP under the control of cAMP-responsive elements. In this system, the polyglutamine stretch repressed cAMP-responsive-element-mediated transcription without the formation of macroscopic expanded polyglutamine aggregates. Furthermore, aggregate formation did not have an adverse effect on the repression of transcriptional activity. The results demonstrated that the repression of cAMP-responsive-element-mediated transcription is an early event caused by a soluble form of polyglutamine stretch. (c) 2005 Lippincott Williams T Wilkins.

    DOI: 10.1097/00001756-200502280-00019

    Web of Science

    PubMed

    researchmap

  • Evaluation of two patients with SCA2 with frontal lobe dysfunction using brain SPECT with three-dimensional stereotactic surface projections (3D-SSP) Reviewed

    Takayoshi Shimohata, Yoko Matsuzawa, Koumei Tanaka, Osamu Onodera, Keiko Tanaka, Masatoyo Nishizawa

    Clinical Neurology   45 ( 1 )   22 - 26   2005.1

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We evaluated the cognitive impairment of two patients with genetically confirmed spinocerebellar ataxia type 2 (SCA2). Neurological examination revealed ignorance of his illness and Gegenhalten phenomenon in patient 1, and emotional incontinence in patient 2. Although their mental status evaluated by HDS-R or Mini-Mental State Examination (MMSE) was almost normal, the results of WAIS-R and Wisconsin Card Sorting Test (WCST) revealed the existence of intellectual decline and executive dysfunction. 3D-SSP SPECT demonstrated distinct hypoperfusion in bilateral frontal lobes, whereas brain MRI revealed no apparent cerebral atrophy in both patients. These results raise the possibility that frontal lobe dysfunction was observed in the early stages of SCA2, and that 3D-SSP SPECT is useful for evaluating the involvement of frontal lobe dysfunction in SCA2.

    Scopus

    PubMed

    researchmap

  • The FHA domain of aprataxin interacts with the C-terminal region of XRCC1 Reviewed

    H Date, S Igarashi, Y Sano, T Takahashi, T Takahashi, H Takano, S Tsuji, M Nishizawa, O Onodera

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   325 ( 4 )   1279 - 1285   2004.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Aprataxin (APTX) is the causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH/AOA1). In our previous study, we found that APTX interacts with X-ray repair cross-complementing group 1 (XRCC1), a scaffold protein with an essential role in single-strand DNA break repair (SSBR). To further characterize the functions of APTX, we determined the domains of APTX and XRCC1 required for the interaction. We demonstrated that the 20 N-terminal amino acids of the FHA domain of APTX are important for its interaction with the C-terminal region (residues 492-574) of XRCC1. Moreover, we found that poly (ADP-ribose) polymerase-1 (PARP-1) is also co-immunoprecipitated with APTX. These findings suggest that APTX, together with XRCC1 and PARP-1, plays an essential role in SSBR. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.10.162

    Web of Science

    PubMed

    researchmap

  • Clinical spectrums of SCA 17 depend on length of CAA/CAG repeat units in the TBP gene. Reviewed

    Toyoshima Y, Yamada M, Onodera O, Shimohata M, Inenaga C, Fujita N, Morita M, Tsuji S, Takahashi H

    Annals of Neurology   56   163 - 164   2004.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    researchmap

  • beta-Synuclein gene alterations in dementia with Lewy bodies Reviewed

    H Ohtake, P Limprasert, Y Fan, O Onodera, A Kakita, H Takahashi, LT Bonner, DW Tsuang, IVJ Murray, VMY Lee, JQ Trojanowski, A Ishikawa, J Idezuka, M Murata, T Toda, TD Bird, JB Leverenz, S Tsuji, AR La Spada

    NEUROLOGY   63 ( 5 )   805 - 811   2004.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: To determine whether mutations in the genes for alpha-synuclein or beta-synuclein are responsible for dementia with Lewy bodies ( DLB), a disorder closely related to Parkinson disease (PD). Methods: The authors ascertained 33 sporadic cases of DLB and 10 kindreds segregating DLB. DNA samples from the 43 index cases were screened for alterations in the genes for alpha-synuclein and beta-synuclein, as alpha-synuclein alterations cause PD and beta-synuclein may modulate alpha-synuclein aggregation and neurotoxicity. Results: Two amino acid alterations were identified in unrelated DLB index cases: a valine to methionine substitution at codon 70 (V70M) and a proline to histidine substitution at codon 123 (P123H), both in the beta-synuclein gene. These amino acid substitutions occur at conserved residues in highly conserved regions of the beta-synuclein protein. Screening of at least 660 chromosomes from control subjects matched to the patients' population groups failed to identify another V70M or P123H allele. Cosegregation analysis of an extended pedigree segregating the P123H beta-synuclein alteration suggested that it is a dominant trait with reduced penetrance or a risk factor polymorphism. Histopathology and immunohistochemistry analysis of index case brain sections revealed widespread Lewy body pathology and alpha-synuclein aggregation without evidence of beta-synuclein aggregation. Conclusion: Mutations in the beta-synuclein gene may predispose to DLB.

    Web of Science

    PubMed

    researchmap

  • Quantitative evaluation of brainstem involvement in multiple system atrophy by diffusion-weighted MR imaging Reviewed

    M Kanazawa, T Shimohata, K Terajima, O Onodera, K Tanaka, S Tsuji, K Okamoto, M Nishizawa

    JOURNAL OF NEUROLOGY   251 ( 9 )   1121 - 1124   2004.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:DR DIETRICH STEINKOPFF VERLAG  

    In multiple system atrophy (MSA), symptoms associated with dysfunctions of the brainstem and autonomic nervous system are important prognostic factors. We investigated brainstem involvement in 12 patients with MSA with predominant cerebellar symptoms (MSA-C) (mean age, 56.3 +/- 9.9 years, median disease duration, 3 years), and 11 controls (57.6 +/- 12.0 years) matched for age using diffusion-weighted MR imaging (DWI). We demonstrated that apparent diffusion coefficients (ADCs) in the pons and middle cerebellar peduncle of MSA-C patients are significantly higher than those of normal controls even though the patients are in the early stage of the disease. Furthermore, we demonstrated that increased ADC values correlated well with the disease duration. The current study demonstrated that DWI is a useful noninvasive method for the quantitative evaluation of the brainstem involvement in MSA-C patients.

    DOI: 10.1007/s00415-004-0494-0

    Web of Science

    PubMed

    researchmap

  • Five year follow up of a patient with spinal and bulbar muscular atrophy treated with leuprorelin Reviewed

    T Shimohata, T Kimura, M Nishizawa, O Onodera, S Tsuji

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   75 ( 8 )   1206 - 1207   2004.8

     More details

    Language:English   Publisher:B M J PUBLISHING GROUP  

    DOI: 10.1136/jnnp.2003.030064

    Web of Science

    PubMed

    researchmap

  • Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5 Reviewed

    H Ohtake, T Shimohata, K Terajima, T Kimura, R Jo, R Kaseda, O Iizuka, M Takano, Y Akaiwa, H Goto, H Kobayashi, T Sugai, T Muratake, T Hosoki, T Shioiri, K Okamoto, O Onodera, K Tanaka, T Someya, T Nakada, S Tsuji

    NEUROLOGY   62 ( 9 )   1601 - 1603   2004.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.

    Web of Science

    PubMed

    researchmap

  • Disruption of the toxic conformation of the expanded polyglutamine stretch leads to suppression of aggregate formation and cytotoxicity Reviewed

    HA Popiel, Y Nagai, O Onodera, T Inui, N Fujikake, Y Urade, WJ Strittmatter, Burke, JR, A Ichikawa, T Toda

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   317 ( 4 )   1200 - 1206   2004.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The polyglutamine (polyQ) diseases are a class of inherited neurodegenerative diseases including Huntington's disease, caused by the expansion of a polyQ stretch within each disease protein. This expansion is thought to cause a conformational change in the protein leading to aggregation of the protein, resulting in cytotoxicity. To analyze whether disrupting the toxic conformation of the polyQ protein can alter its aggregation propensity and cytotoxicity, we examined the effect of interruption of the expanded polyQ stretch by proline insertion, since prolines cause great alterations in protein conformation. Here, we show that insertion of prolines into the expanded polyQ stretch indeed disrupts its ordered secondary structure, leading to suppression of polyQ protein aggregation both in vitro and in cell culture, and reduction of cytotoxicity in correlation with the number of proline interruptions. Furthermore, we found that a short polyQ stretch with a proline interruption is able to inhibit aggregation of the expanded polyQ protein in trans. These results show that a gain in toxic conformation of the expanded polyQ protein is essential for aggregation and cytotoxicity, providing insight into establishing therapies against the polyQ diseases. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.03.161

    Web of Science

    PubMed

    researchmap

  • Aprataxin, a novel protein that protects against genotoxic stress Reviewed

    N Gueven, OJ Becherel, AW Kijas, P Chen, O Howe, JH Rudolph, R Gatti, H Date, O Onodera, G Taucher-Scholz, MF Lavin

    HUMAN MOLECULAR GENETICS   13 ( 10 )   1081 - 1093   2004.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Ataxia-oculomotor apraxia (AOA1) is a neurological disorder with symptoms that overlap those of ataxia-telangiectasia, a syndrome characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, is predicted to code for a protein called aprataxin that contains domains of homology with proteins involved in DNA damage signalling and repair. We demonstrate that aprataxin is a nuclear protein, present in both the nucleoplasm and the nucleolus. Mutations in the APTX gene destabilize the aprataxin protein, and fusion constructs of enhanced green fluorescent protein and aprataxin, representing deletions of putative functional domains, generate highly unstable products. Cells from AOA1 patients are characterized by enhanced sensitivity to agents that cause single-strand breaks in DNA but there is no evidence for a gross defect in single-strand break repair. Sensitivity to hydrogen peroxide and the resulting genome instability are corrected by transfection with full-length aprataxin cDNA. We also demonstrate that aprataxin interacts with the repair proteins XRCC1, PARP-1 and p53 and that it co-localizes with XRCC1 along charged particle tracks on chromatin. These results demonstrate that aprataxin influences the cellular response to genotoxic stress very likely by its capacity to interact with a number of proteins involved in DNA repair.

    DOI: 10.1093/hmg/ddh122

    Web of Science

    PubMed

    researchmap

  • Gene diagnosis of patients with chorea Reviewed

    Takayoshi Shimohata, Osamu Onodera, Yoshiaki Honma, Koichi Hirota, Yasuhito Nunomura, Tetsuya Kimura, Izumi Kawachi, Kazuhiro Sanpei, Masatoyo Nishizawa, Shoji Tsuji

    Clinical Neurology   44 ( 3 )   149 - 153   2004.3

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    To elucidate the etiology of chorea, we performed gene diagnoses of 79 consecutive cases of the disease (34 males, 45 females
    age 15-79 years), which include 39 familial cases (37 pedigrees) and 40 sporadic cases, from 1997 to 2002, after their informed consent was obtained. We extracted genomic DNA from peripheral white blood cells, and performed genetic tests for Huntington disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), Huntington disease like 1 (HDL1), HDL2 and spinocerebellar ataxia type 17 (SCA17). We found 37 cases (36 pedigrees) of HD, seven cases (seven pedigrees) of DRPLA. No cases of HDL1, HDL2 and SCA17 were found. We also found three cases (two pedigrees) presenting an autosomal dominant trait with an unknown origin, and two cases whose parents were consanguineously related. Therefore, further genetic heterogeneity is expected in the cases of chorea in Japan.

    Scopus

    PubMed

    researchmap

  • Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein Reviewed

    Y Sano, H Date, S Igarashi, O Onodera, M Oyake, T Takahashi, S Hayashi, M Morimatsu, H Takahashi, T Makifuchi, N Fukuhara, S Tsuji

    ANNALS OF NEUROLOGY   55 ( 2 )   241 - 249   2004.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long-form aprataxin is essential for its nuclear localization. We found, based on the yeast two-hybrid and coimmunoprecipitation experiments, that the long-form but not the short-form aprataxin interacts with XRCC1 (x-ray repair cross-complementing group 1). Interestingly the amino terminus of the long-form aprataxin is homologous with polynucleotidekinase-3'-phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single-strand DNA break repair, through interaction with XRCC1, DNA polymerase beta, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single-strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.

    DOI: 10.1002/ana.10808

    Web of Science

    PubMed

    researchmap

  • SCA17 homozygote showing Huntington's disease-like phenotype Reviewed

    Y Toyoshima, M Yamada, O Onodera, M Shimohata, C Inenaga, N Fujita, M Morita, S Tsuji, H Takahashi

    ANNALS OF NEUROLOGY   55 ( 2 )   281 - 286   2004.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    We report a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was not lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.

    DOI: 10.1002/ana.10824

    Web of Science

    PubMed

    researchmap

  • Spinocerebellar ataxia type 17 repeat in patients with huntington's disease-like and ataxia [1] (multiple letters)

    Cellini, E., Forleo, P., Nacmias, B., Tedde, A., Bagnoli, S., Piacentini, S., Sorbi, S., Toyoshima, Y., Yamada, M., Onodera, O., Shimohata, M., Inenaga, C., Fujita, N., Morita, M., Tsuji, S., Takahashi, H.

    Annals of Neurology   56 ( 1 )   2004

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    researchmap

  • Two Cases of Generalized Tetanus Presenting with Dysphagia as an Initial Symptom Reviewed

    Masato Kanazawa, Hideaki Ishiguro, Osamu Onodera, Kenjiro Yoshikawa, Takashi Koide, Aki Arai, Arika Hasegawa, Ryouichi Nakano, Keiko Tanaka, Masatoyo Nishizawa

    Brain and Nerve   55 ( 11 )   973 - 976   2003.11

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.

    Scopus

    PubMed

    researchmap

  • Severe generalized dystonia as a presentation of a patient with aprataxin gene mutation Reviewed

    Y Sekijima, T Hashimoto, O Onodera, H Date, T Okano, K Naito, S Tsuji, S Ikeda

    MOVEMENT DISORDERS   18 ( 10 )   1198 - 1200   2003.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    A 14-year-old girl, homozygous for an insertion mutation of aprataxin (APTX), 689 ins T, is described. She presented with severe generalized dystonia, ataxia, ocular motor apraxia, and areflexia. The dystonia of this patient suggests involvement of the basal ganglia or thalamus, along with clinical diversity in this disorder. 0 2003 Movement Disorder Society.

    DOI: 10.1002/mds.10526

    Web of Science

    PubMed

    researchmap

  • Steroid-pulse therapy in Guillain-Barré syndrome associated with cytomegalovirus infection: A case report Reviewed

    Masayoshi Tada, Osamu Onodera, Izumi Kawachi, Kenju Hara, Masahisa Sato, Hiide Yoshino, Atsuko Asano, Yoshiaki Soma, Shoji Tsuji

    Brain and Nerve   55 ( 7 )   615 - 621   2003.7

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report a 27-year-old man with Guillain-Barré syndrome (GBS) preceded by cytomegalovirus infection. He was admitted to our hospital because of distal dominant weakness and sensory disturbance 5 days after fever. Double filtration plasmapheresis (DFPP) was performed and clinical symptoms temporary but dramatically improved. However facial nerve palsy, difficulty in swallowing food, weakness, dysautonomia and respiratory failure rapidly progressed within 5 days áfter the onset. Repeated DFPP failed to improve his symptoms. Two months after the onset, he did not improve at all. On T1-weighted MRI, nerve roots were still enhanced with gadolinium, and CSF examination revealed 1,324 mg/dl of protein. These findings suggested us the existence of continuous inflammation on nerve roots. We gave steroid-pulse therapy. He dramatically improved after this treatment. We repeated steroid-pulse therapy for seven times. He was discharged without any major complication 6 months after the onset. Steroid-pulse therapy should be considered in GBS patients associated with CMV infection when other conventional treatments are ineffective.

    Scopus

    PubMed

    researchmap

  • Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients Reviewed

    N Hattori, M Yamamoto, T Yoshihara, H Koike, M Nakagawa, H Yoshikawa, A Ohnishi, K Hayasaka, O Onodera, M Baba, H Yasuda, T Saito, K Nakashima, J Kira, R Kaji, N Oka, G Sobue

    BRAIN   126 ( Pt 1 )   134 - 151   2003.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

    DOI: 10.1093/brain/awg012

    Web of Science

    PubMed

    researchmap

  • Current states of molecular diagnosis of neurodegenerative disorders

    Onodera, O.

    Japanese Journal of Clinical Radiology   48 ( 4 )   2003

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    researchmap

  • A study of shock wave interaction with a rotating cylinder

    Sun, M., Yada, K., Jagadeesh, G., Onodera, O., Ogawa, T., Takayama, K.

    Shock Waves   12 ( 6 )   2003

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00193-003-0183-4

    Scopus

    researchmap

  • Neuropathological features in corticobasal degeneration and progressive supranuclear palsy

    WAKABAYASHI Koichi, TAKAHASHI Hitoshi, Takahashi Hitoshi, Onodera Osamu, Nishizawa Masatoyo

    Rinsho Shinkeigaku   42 ( 11 )   1155 - 1157   2002.11

     More details

    Language:Japanese   Publisher:Societas Neurologica Japonica  

    TDP-43 is a nuclear protein that plays a role in RNA metabolism, and its dysfunction has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a typical adult-onset motor neuron disease. We investigated RNA metabolism in relation to TDP-43 function in neuronal tissues affected by ALS, and found a decrease in the number of nuclear GEM bodies, as well as reduced expression of minor spliceosomes, which are functional RNA-protein complexes. Similar features have been reported in spinal muscular atrophy (SMA), a motor neuron disease affecting infants. These findings, together with those reported in SMA, strongly suggest that reduction of minor spliceosomes has an important role in the pathomechanism underlying the selective degeneration of motor neurons characteristic of both ALS and SMA.

    DOI: 10.5692/clinicalneurol.54.1155

    CiNii Article

    CiNii Books

    researchmap

    Other Link: https://jlc.jst.go.jp/DN/JLC/20005129827?from=CiNii

  • Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a T666M mutation in the CACNA1A gene Reviewed

    T Takahashi, S Igarashi, T Kimura, Hozumi, I, Kawachi, I, O Onodera, H Takano, M Saito, S Tsuji

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   72 ( 5 )   676 - 677   2002.5

     More details

    Language:English   Publisher:BRITISH MED JOURNAL PUBL GROUP  

    DOI: 10.1136/jnnp.72.5.676

    Web of Science

    PubMed

    researchmap

  • Expanded polyglutamine stretches form an 'aggresome' Reviewed

    T Shimohata, A Sato, Burke, JR, WJ Strittmatter, S Tsuji, O Onodera

    NEUROSCIENCE LETTERS   323 ( 3 )   215 - 218   2002.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCI IRELAND LTD  

    To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with gamma-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules (MTs) with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on MTs to the MTOC, where they remain as distinct 'aggresomes'. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00162-3

    Web of Science

    PubMed

    researchmap

  • Time course of polyglutamine aggregate body formation and cell death: Enhanced growth in nucleus and an interval for cell death Reviewed

    Toyoshima, I, M Sugawara, K Kato, C Wada, T Shimohata, R Koide, O Onodera, S Tsuji

    JOURNAL OF NEUROSCIENCE RESEARCH   68 ( 4 )   442 - 448   2002.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral-pallidoluysian atrophy and related neurodegenerative disorders, although the relationship between aggregate body formation and cell death is not clear. We analyzed the kinetics of polyQ aggregate formation and the time intervals for cell death, tracking individual cells using fluorescence video microscopy, for the first time. Expanded polyQ tracts of atrophin-1 with or without nuclear localization signal (NLS) labeled with green fluorescent protein (GFP) were constructed, Q57NLS/GFP and Q56/GFP, respectively. All of the Q57NLS/GFP aggregate bodies were in nuclei, and all of the Q56/GFP aggregate bodies were in cytoplasm. Aggregates of Q56/GFP were larger than those of Q57NLS/ GFP. Surprisingly, a kinetic analysis showed that the latter grew 5.37 times faster than the former. The time interval between transfection and cell death was shorter in Q57NLS/GFP, but the time between the end of the rapid growing phase of aggregation and the start of the cell death process did not show a significant difference. Aggregate growth was confirmed to correspond to the accumulated free polyQ by the time of starting aggregation. These findings suggest that aggregate body formation induced by expanded polyQ stretches is a self-limiting process and is enhanced by factor(s) in nuclei, whereas it is not tightly bound to the cell death process. (C) 2002 Wiley-Liss,

    DOI: 10.1002/jnr.10233

    Web of Science

    PubMed

    researchmap

  • Epidemiology of X-linked adrenoleukodystrophy in Japan Reviewed

    Y Takemoto, Y Suzuki, A Tamakoshi, O Onodera, S Tsuji, T Hashimoto, N Shimozawa, T Orii, N Kondo

    JOURNAL OF HUMAN GENETICS   47 ( 11 )   590 - 593   2002

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER-VERLAG TOKYO  

    To clarify the epidemiology of X-linked adrenoleukodystrophy (ALD) in Japan, we performed a questionnaire survey. Two hundred eighty-six patients, including 154 from internal medicine, 100 from pediatrics, 21 from psychiatry, and I I from other hospitals, were reported to have ALD between 1990 and 1999. The data on 154 patients revealed the phenotypic distribution to be as follows: childhood cerebral form (29.9%), adrenomyeloneuropathy (25.3%), adult cerebral form (21.4%), adolescent form (9.1%), olivo-ponto-cerebellar form (8.4%), presymptomatic form (4.5%), and symptomatic female patient (1.3%). The adult cerebral form and olivo-ponto-cerebellar form were more common in Japan than in North America and Europe. The incidence of X-linked ALD in Japan was estimated to be between 1: 30 000 and 1: 50 000 boys, similar to previous reports. About half of the patients with adrenomyeloneuropathy and the olivo-ponto-cerebellar phenotype developed cerebral involvement with a mean interval of 8.2 and 2.2 years after ALD onset, respectively. The family histories revealed that brothers and first cousins tended to show similar phenotypes, whereas nephews tended to develop symptoms earlier than uncles. These data will help in understanding the natural history of X-linked ALD.

    DOI: 10.1007/s100380200090

    Web of Science

    PubMed

    researchmap

  • Paraneoplastic striatal encephalitis Reviewed

    T Oguma, H Kobayashi, S Katada, O Onodera, K Tanaka, S Tsuji, T Uno, T Ishida, H Kagamu, F Gejyo, M Motomura

    NEUROLOGY   57 ( 12 )   2326 - 2326   2001.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    PubMed

    researchmap

  • Amino acid sequences flanking polyglutamine stretches influence their potential for aggregate formation Reviewed

    K Nozaki, O Onodera, H Takano, S Tsuji

    NEUROREPORT   12 ( 15 )   3357 - 3364   2001.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Expanded polyglutamine stretches have been shown to form aggregates and to be toxic to cells. In this study, we hypothesized that amino acid sequences flanking the polyglutamine stretches influence the aggregate formation potential of these stretches. Green fluorescent protein (GFP) fusion proteins containing glutamine repeats of various lengths and a fixed number of flanking amino acids of ataxin-2, huntingtin, clentatorubral-pallidoluysian atrophy protein (DRPLAP) or ataxin-3 were transiently expressed in COS-7 cells. The aggregate formation potential of ataxin-2 and DRPLAP increased in a CAG-repeat-length-dependent manner, with a threshold between 34 and 36. Truncated ataxin-2-Q56-GFP and truncated huntingtin-Q56-GFP showed a significantly higher aggregate formation potential than truncated DRPLAP-Q56-GFP or truncated ataxin-3-Q56-GFP. These results are in agreement with the clinical observation that ages of disease onset in patients with spinocerebellar ataxia type 2 or Huntington's disease are lower than those in patients with DRPLA or Machado-Joseph disease having expanded CAG repeats of the same length. Furthermore, mutagenesis of the flanking sequence of ataxin-2 markedly reduced its aggregate formation potential. These results indicate that the amino acid sequences flanking the polyglutamine stretches significantly influence their aggregate formation potential. NeuroReport 12:3357-3364 (C) 2001 Lippincott Williams & Wilkins.

    Web of Science

    PubMed

    researchmap

  • Expanded polyglutamine stretches lead to aberrant transcriptional regulation in polyglutamine diseases. Reviewed

    Shimohata, T., Onodera, O., Tsuji, S.

    Human cell : official journal of Human Cell Research Society   14 ( 1 )   17 - 25   2001.3

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • Micro-shock waves generated inside a fluid jet impinging on plane wall

    Jagadeesh, G., Onodera, O., Ogawa, T., Takayama, K., Jiang, Z.

    AIAA journal   39 ( 3 )   2001

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.2514/2.1352

    Scopus

    researchmap

  • Interaction of expanded polyglutamine stretches with nuclear transcription factors leads to aberrant transcriptional regulation in polyglutamine diseases Reviewed

    T Shimohata, O Onodera, S Tsuji

    NEUROPATHOLOGY   20 ( 4 )   326 - 333   2000.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BLACKWELL SCIENCE ASIA  

    At least eight inherited neurodegenerative diseases are known to be caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches have been suggested, the molecular mechanisms of neurodegeneration remain unclear. The nuclear translocation of mutant proteins containing expanded polyQ stretches has been demonstrated as a prerequisite for the expression of their cytotoxicity. Hypothesizing that nuclear proteins that interact with mutant proteins, particularly, those that bind to the expanded polyQ stretches, are involved in the pathogenetic mechanisms underlying neurodegeneration, nuclear proteins were screened for their capability of binding to expanded polyQ stretches. It was found that expanded polyQ stretches preferentially bind to TAF(II)130, a coactivator involved in cAMP-responsive element-binding protein (CREB)-dependent transcriptional activation. The binding of TAF(II)130 with expanded polyQ stretches strongly suppresses CREB-dependent transcriptional activation, suggesting that interference with transcription due to the binding of expanded polyQ stretches with TAF(II)130 and redistribution of TAF(II)130 are involved in the pathogenetic mechanisms underlying neurodegeneration.

    DOI: 10.1046/j.1440-1789.2000.00350.x

    Web of Science

    PubMed

    researchmap

  • Expanded polyglutamine stretches interact with TAF(II)130, interfering with CREB-dependent transcription Reviewed

    T Shimohata, T Nakajima, M Yamada, C Uchida, O Onodera, S Naruse, T Kimura, R Koide, K Nozaki, Y Sano, H Ishiguro, K Sakoe, T Ooshima, A Sato, T Ikeuchi, M Oyake, T Sato, Y Aoyagi, Hozumi, I, T Nagatsu, Y Takiyama, M Nishizawa, J Goto, Kanazawa, I, Davidson, I, N Tanese, H Takahashi, S Tsuji

    NATURE GENETICS   26 ( 1 )   29 - 36   2000.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded! polyQ stretches preferentially bind to TAF(II)130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAF(II)130. Our results indicate that interference of transcription by the binding of TAF(II)130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.

    DOI: 10.1038/79139

    Web of Science

    PubMed

    researchmap

  • Mutational Analysis of X-Linked Adrenoleukodystrophy Gene Reviewed

    Hiroki Takano, Ryoko Koike, Osamu Onodera, Shoji Tsuji

    Cell Biochemistry and Biophysics   32   177 - 185   2000

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Humana Press  

    X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal disorder characterized by progressive neurological dysfunction, occasionally associated with adrenal insufficiency. The clinical phenotypes of ALD are quite variable, and include childhood ALD, adult-onset ALD, adrenomyeloneuropathy, and Addison's disease only. Although the causative gene for ALD has been identified, the physiological role of the gene product remains to be clarified. Despite many mutations having been identified in patients with these clinical phenotypes, the genotype-phenotype correlations have not been clarified. The authors investigated genotype-phenotype correlatons in ALD by analyses on 29 unrelated Japanese patients with ALD and by a review of the literature. All the phenotypes were associated with mutations leading to protein truncation, as well as those resulting in subtle amino acid changes. Furthermore, there were no differences in phenotypic expression among the natures of the subtle amino acid changes. All these data indicate that no obvious correlations exist between the phenotypes of ALD patients and their geneotypes, suggesting that other genetic or environmental factors may also be involved in determining phenotypic expression in ALD.

    DOI: 10.1385/CBB:32:1-3:177

    Scopus

    PubMed

    researchmap

  • Characteristics of an annular vertical diaphragmless shock tube

    Hosseini, S.H.R., Onodera, O., Takayama, K.

    Shock Waves   10 ( 3 )   2000

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s001930050001

    Scopus

    researchmap

  • No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy Reviewed

    T Ozawa, H Takano, O Onodera, H Kobayashi, T Ikeuchi, R Koide, K Okuizumi, T Shimohata, K Wakabayashi, H Takahashi, S Tsuji

    NEUROSCIENCE LETTERS   270 ( 2 )   110 - 112   1999.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCI IRELAND LTD  

    To determine whether mutations in the coding region of the alpha-synuclein gene are relevant in cases of multiple system atrophy (MSA), detailed nucleotide sequence analysis of the alpha-synuclein gene was performed using total RNA obtained from autopsied brain specimens of 11 pathologically confirmed cases of MSA. The brain specimens used in this study contained both gray and white matter, which were dissected from the frontal, temporal or occipital lobe. No nucleotide alterations were found in the entire coding region of the alpha-synuclein gene in any of the cases. While mutations In the regulatory or intronic regions of the gene were not ruled out, our results suggest that mutations in the coding region of the alpha-synuclein gene are unlikely to contribute to the pathogenesis of MSA. (C) 1999 Elsevier Science ireland ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(99)00475-9

    Web of Science

    PubMed

    researchmap

  • Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy Reviewed

    H Takano, R Koike, O Onodera, R Sasaki, S Tsuji

    ARCHIVES OF NEUROLOGY   56 ( 3 )   295 - 300   1999.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER MEDICAL ASSOC  

    Background: X-linked adrenoleukodystrophy (ALD) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. The classic form of AID usually has onset in childhood (childhood cerebral ALD), with rapid neurologic deterioration leading to a vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and Addison disease only also have been recognized. Despite discovery of the causative gene, a molecular basis for the diverse clinical presentations remains to be elucidated.
    Objectives: To conduct mutational analyses in 29 Japanese patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum of mutations in this gene, and to study genotype-phenotype correlations in Japanese patients.
    Methods: The 29 patients comprised 13 patients with childhood cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated Japanese patients with ALD by genomic Southern blot analysis and direct nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction products derived from total RNA that was extracted from cultured skin fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes.
    Results: Three patients with adult-onset cerebral ALD were identified as having large genomic rearrangements. The remaining 26 patients were identified as having 21 independent mutations, including 12 novel mutations resulting in small nucleotide alterations in the ALD gene, Eighteen (69%) of 26 mutations were missense mutations. Most missense mutations involved amino acids conserved in homologous gene products, including PMF70, mALDRP, and Pxa1p. The AG dinucleotide deletion at position 1081-1082, which has been reported previously to be the most common mutation in white patients (12-17%), was also identified as the most common mutation in Japanese patients (12%). All phenotypes were associated with mutations resulting in protein truncation or subtle amino acid changes. There were no differences in phenotypic expressions between missense mutations involving conserved amino acids and those involving nonconserved amino acids.
    Conclusion: There are no obvious correlations be tween the phenotypes of patients with ALD and their genotypes, suggesting that other genetic or environmental factors modify the phenotypic expressions of ALD.

    Web of Science

    PubMed

    researchmap

  • Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network Reviewed

    Y Nagai, O Onodera, J Chun, WJ Strittmatter, Burke, JR

    EXPERIMENTAL NEUROLOGY   155 ( 2 )   195 - 203   1999.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC  

    Eight inherited neurodegenerative diseases are caused by genes with expanded CAG; repeats coding for polyglutamine domains in the disease-producing proteins. The mechanism by which this expanded polyglutamine domain causes neurodegenerative disease is unknown, but nuclear and cytoplasmic polyglutamine protein aggregation is a common feature. In transfected COS7 cells, expanded polyglutamine proteins aggregate and disrupt the vimentin intermediate filament network. Since neurons have an intermediate filament network composed of neurofilament (NF) and NF abnormalities occur in neurodegenerative diseases, we examined whether pathologic-length polyglutamine domain proteins also interact with NF. We expressed varying lengths polyglutamine-green fluorescent protein fusion proteins in a neuroblast cell line, TR1. Pathologic-length polyglutamine-GFP fusion proteins formed large cytoplasmic aggregates surrounded by neurofilament. Immunoisolation of pathologic-length polyglutamine proteins coisolated 68-kDa NF protein demonstrating molecular interaction. These observations suggest that polyglutamine interaction with NF is important in the pathogenesis of the polyglutamine repeat diseases. (C) 1999 Academic Press.

    DOI: 10.1006/exnr.1998.6991

    Web of Science

    PubMed

    researchmap

  • Generation of neuronal intranuclear inclusions by polyglutamine-GFP: Analysis of inclusion clearance and toxicity as a function of polyglutamine length Reviewed

    KL Moulder, O Onodera, Burke, JR, WJ Strittmatter, EM Johnson

    JOURNAL OF NEUROSCIENCE   19 ( 2 )   705 - 715   1999.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    Recent evidence suggests that, in huntingtin and many other proteins, polyglutamine repeats are a toxic stimulus in neurodegenerative diseases. To investigate the mechanism by which these repeats may be toxic, we transfected primary rat cerebellar granule neurons with polyglutamine-green fluorescent protein (GFP) fusion constructs containing 19 (Q19-GFP), 35 (Q35-GFP), 56 (Q56-GFP), or 80 (Q80-GFP) glutamine residues. All constructs, except Q19-GFP, aggregated within the nuclei of transfected cells in a length- and time-dependent manner. Although Q35-GFP expression led to the development of several small aggregates per cell, these aggregates were cleared or degraded, and the cells remained viable. In contrast, Q80-GFP expression resulted in one or two large aggregates and induced cell death. Caspase activation was observed after Q80-GFP aggregation, but inhibition of caspases with Boc-aspartyl-(OMe)-fluoromethylketone (BAF) only served to delay, not prevent, toxicity. In addition, aggregation and toxicity were not affected by other modulators of neuronal cell death such as genetic deletion of the proapoptotic bcl-2 family member bax or addition of the protein synthesis inhibitor cycloheximide. Lastly, nuclear condensation did not occur as part of the toxicity. These data suggest that polyglutamine-GFP expression is toxic to primary neurons but that the death is distinct from classical apoptosis.

    Web of Science

    PubMed

    researchmap

  • Polyglutamine domain proteins with expanded repeats bind neurotilament, altering the neurofilament network Reviewed

    Y Nagai, O Onodera, WJ Strittmatter, Burke, JR

    OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS   893   192 - 202   1999

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NEW YORK ACAD SCIENCES  

    Proteins with expanded polyglutamine (polyQ) repeats cause eight inherited neurodegenerative diseases, Nuclear and cytoplasmic polyQ protein is a common feature of these diseases, but its role in cell death remains debatable. Since the neuronal intermediate filament network is composed of neurofilament (NF) and NF abnormalities occur in neurodegenerative diseases, we examined whether pathologic-length polyQ domain proteins interact with NF. me expressed polyQ-green fluorescent fusion proteins (GFP) in a neuroblast cell line, TR1. Pathologic-length polyQ-GFP fusion proteins form large cytoplasmic aggregates surrounded by neurofilament, Immunoisolation of pathologic-length polyQ proteins co-isolated 68 kD NF protein demonstrating molecular interaction. These observations suggest that polyQ interaction with NF is important in the pathogenesis of the polyglutamine repeat disease.

    DOI: 10.1111/j.1749-6632.1999.tb07826.x

    Web of Science

    PubMed

    researchmap

  • Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients Reviewed

    Toshiya Sato, Mutsuo Oyake, Kenji Nakamura, Kazuki Nakao, Yoshimitsu Fukusima, Osamu Onodera, Shuichi Igarashi, Hiroki Takano, Koki Kikugawa, Yoshinori Ishida, Takayoshi Shimohata, Reiji Koide, Takeshi Ikeuchi, Hajime Tanaka, Naonobu Futamura, Ryusuke Matsumura, Tetsuya Takayanagi, Fumiaki Tanaka, Gen Sobue, Osamu Komure, Mie Takahashi, Akira Sano, Yaeko Ichikawa, Jun Goto, Ichiro Kanazawa, Motoya Katsuki, Shoji Tsuji

    Human Molecular Genetics   8 ( 1 )   99 - 106   1999

     More details

    Publishing type:Research paper (scientific journal)  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is one among an increasing number of hereditary neurodegenerative diseases determined as being caused by unstable expansion of CAG repeats coding for polyglutamine stretches. To investigate the molecular mechanisms underlying CAG repeat instability, we established three transgenic lines each harboring a single copy of a full-length human mutant DRPLA gene carrying a CAG repeat expansion. These transgenic mice exhibited an age-dependent increase (+0.31 per year) in male transmission and an age-dependent contraction (-1.21 per year) in female transmission. Similar tendencies in intergenerational instabilities were also observed in human DRPLA parent-offspring pairs. The intergenerational instabilities of the CAG repeats may be interpreted as being derived from the instability occurring during continuous cell division of spermatogonia in the male, and that occurring during the period of meiotic arrest in the female. The transgenic mice also exhibited an age-dependent increase in the degree of somatic mosaicism which occurred in a cell lineage-dependent manner, with the size range of CAG repeats being smaller in the cerebellum than in other tissues including the cerebrum, consistent with observations in autopsied tissues of DRPLA patients. Thus, the transgenic mice described in this study exhibited age-dependent intergenerational as well as somatic instabilities of expanded CAG repeats comparable with those observed in human DRPLA patients, and are therefore expected to serve as good models for investigating the molecular mechanisms of instabilities of CAG repeats.

    DOI: 10.1093/hmg/8.1.99

    Scopus

    PubMed

    researchmap

  • Application of shock wave research to geophysics

    Takayama, K., Onodera, O., Saito, T.

    Journal of Materials Processing Technology   85 ( 1-3 )   1999

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S0924-0136(98)00244-1

    Scopus

    researchmap

  • Evolution of shock waves and the primary vortex loop discharged from a square cross-sectional tube

    Jiang, Z., Onodera, O., Takayama, K.

    Shock Waves   9 ( 1 )   1999

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s001930050133

    Scopus

    researchmap

  • Stability of converging cylindrical shock waves in a vertical annular co-axial diaphragmless shock tube

    Hosseini, S.H.R., Onodera, O., Takayama, K.

    Transactions of the Japan Society for Aeronautical and Space Sciences   42 ( 135 )   1999

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    researchmap

  • Efficacy of early plasmapheresis in Bickerstaff's encephalitis Reviewed

    T Ozawa, O Onodera, T Inuzuka, Y Soma, S Tsuji

    INTERNAL MEDICINE   37 ( 11 )   986 - 989   1998.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPAN SOC INTERNAL MEDICINE  

    Double filtration plasmapheresis (DFPP) was performed in a patient with Bickerstaff's brainstem encephalitis (BBE) in its early phase. He was a 27-year-old male patient suffering from diplopia, facial palsy and drowsiness following upper respiratory tract infection, and had high titers of immunoglobulin G (IgG) antibodies against ganglioside NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer (GQ1b) in the serum, DFPP effected immediate improvement of his drowsiness, supporting the diagnosis of BBE, Our observations suggest that DFPP during the early phase of BBE efficiently prevents the progression of consciousness disturbances.

    DOI: 10.2169/internalmedicine.37.986

    Web of Science

    PubMed

    researchmap

  • A Japanese family with adrenoleukodystrophy with a codon 291 deletion: A clinical, biochemical, pathological, and genetic report Reviewed

    S Kano, M Watanabe, M Kanai, R Koike, O Onodera, S Tsuji, K Okamoto, M Shoji

    JOURNAL OF THE NEUROLOGICAL SCIENCES   158 ( 2 )   187 - 192   1998.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    We report a Japanese family with adrenoleukodystrophy (ALD) with a three base pair deletion (delGAG291) in the ALD gene. A variety of phenotypes were observed within this family. While the proband (patient 1) was classified as having a rare intermediate type of adult cerebral and cerebello-brain stem forms, his younger brother (patient 2) and nephew (patient 3) had a childhood ALD type. Another nephew (patient 4) of patient 1 was classified as having an adolescent form. The tau level in the cerebrospinal fluid (CSF) in patient 1 was as high as that of patients with Alzheimer's disease (AD). His brain magnetic resonance image (MRI) showed abnormalities in the bilateral cerebellar hemispheres and brain stem, but not in the cerebral white matter, where marked reductions of the cerebral blood flow and oxygen metabolism were clearly demonstrated by positron emission tomography (PET). In patients 2 and 3, the autopsy findings showed massive demyelination of the cerebral white matter with sparing of the U-fibers, compatible with the findings of childhood ALD. Oleic and erucic acids (Lorenzo's Oil) were administered to patients 1 and 4, but sufficient effectiveness was not obtained. The findings in this family suggest that delGAG291 is part of the cause of Japanese ALD with phenotypic variations. Moreover, although the scale of the study is limited, there is a possibility that PET can detect an insidious lesion which is undetectable by computed tomogram (CT) or MRI analysis, and that the higher level of tau reflects the process of neuronal degeneration in ALD. Lorenzo's Oil should be given in the early stage. (C) 1998 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0022-510X(98)00120-8

    Web of Science

    PubMed

    researchmap

  • Molecular cloning, structural organization, sequence, chromosomal assignment, and expression of the mouse alpha-N-acetylgalactosaminidase gene Reviewed

    T Herrmann, D Schindler, H Tabe, O Onodera, S Igarashi, A Polack, D Zehnpfennig, S Tsuji

    GENE   211 ( 2 )   205 - 214   1998.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Alpha-N-acetylgalactosaminidase (2-acetamido-2-deoxy-alpha-D-galactoside acetamidodeoxy-galactohydrolase, NAGA; EC 3.2.1.49) deficiency is a recently recognized autosomal recessive lysosomal disease. As a prerequisite for the generation of an animal model, the mouse NAGA gene was cloned and characterized. The NAGA gene was assigned to mouse chromosome 15 band E3, syntenic to the region encompassing the human gene, and NAGA-deficient mutant human cells transfected with the cosmid clone containing the mouse NAGA gene expressed NAGA activity. Comparison of the mouse NAGA nucleotide sequence with the human NAGA sequence predicted that the mouse NAGA gene contains an open reading frame of 1245 bp, comprising nine coding exons and spanning a genomic region of 8258 bp, and a 3' untranslated region of 0.5 kb. The 5' untranslated region was determined in primer extension studies to be 235 bp in length. Nucleotide identity between the human and mouse NAGA exons ranged from 67.4 to 89.5%, with better matches for exons 1-7 than for 8 and 9. The overall amino acid identity between the mouse and human deduced NAGA polypeptides was 82.0%, between those of mouse and chicken 72.9%. Homology was found to only one other mouse gene, i.e. the a-galactosidase A (GALA; EC 3.2.1.22) gene. The amino acid identity ranged from 51.6 to 62.1% in the polypeptide regions corresponding to NAGA exons 2-7 and GALA exons 1-6, but little, if any, in the remainder. These analyses gave emphasis to the strong conservation of the NAGA gene and its origin from an ancestor common with the GALA gene, with NAGA exons 8 and 9 and GALA exon 7 being the most divergent regions in the evolution of the two genes. (C) 1998 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0378-1119(98)00103-6

    Web of Science

    PubMed

    researchmap

  • Apolipoprotein E epsilon 4 allele and progression of cortical Lewy body pathology in Parkinson's disease Reviewed

    K Wakabayashi, A Kakita, S Hayashi, K Okuizumi, O Onodera, H Tanaka, A Ishikawa, S Tsuji, H Takahashi

    ACTA NEUROPATHOLOGICA   95 ( 5 )   450 - 454   1998.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER VERLAG  

    To elucidate whether the apolipoprotein E epsilon 4 allele (APOE4) affects cortical neuropathology in Parkinson's disease (PD), we determined APOE genotypes and quantified the densities of cortical Lewy bodies (LBs), amyloid plaques and neurofibrillary tangles in 22 autopsy-proven PD cases (12 with dementia; 10 without dementia) that were not accompanied by Alzheimer's disease. The APOE4 frequency in the demented patient group was 0.21, which was significantly higher than that in Japanese controls (P &lt; 0.04). LB densities in demented PD patients were significantly higher than those in non-demented PD patients, despite the shorter disease duration in the former. Moreover, plaque density in the temporal cortex and LB density in the cingulate cortex were significantly higher in the group with APOE4 than in that without the allele. There was no difference in tangle density between these two groups. These results suggest that APOE4 may influence the increase in the number of cortical LBs and amyloid plaques in PD. It is possible that when PD occurs in individuals with APOE4 concomitantly evolving cortical LB pathology in a proportion of cases results in limbic (transitional) or neocortical-type LB disease.

    Web of Science

    PubMed

    researchmap

  • A case of chronic enteroviral meningitis and hydrocephalus associated with Bruton type agammaglobulinemia Reviewed

    Tetsutaro Ozawa, Osamu Onodera, Osamu Iizuka, Yoshinori Tanno, Ikuyo Eguchi, Yoshiaki Soma, Shoji Tsuji

    Brain and Nerve   50 ( 2 )   191 - 196   1998.2

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report a 10-year-old boy with chronic enteroviral meningitis associated with agammaglobulinemia (CEMA) and hydrocephalus. He was treated with a low-dose intravenous administration (100 mg/kg/4 weeks) of gammaglobulin (γ-gl) since he was diagnosed as having Bruton type agammaglobulinemia at 1 year of age. At this admission, neurological examination revealed meningeal signs, Babinski sign, frontal signs, urinary incontinence, and mental retardation (IQ=48) which was considered to be a sequela of the enteroviral encephalitis which had occurred in his first year of life. T1-weighted MR imaging of the brain following gadolinium administration revealed a marked dilatation of the lateral ventricles and dense enhancement of the meninges. Enterovirus was detected in the cerebrospinal fluid (CSF) using tissue culture. Histological examination of a biopsied leptomeningeal specimen revealed inflammatory thickening, which was a likely cause of the obstruction to the flow of CSF. The hydrocephalus in this patient was treated with external drainage of CSF from the lateral ventricle. The CEMA was brought into remission by means of the intraventricular administration of γ-gl, at a dose of 125-250 mg/week (total dose: 1.5 g/8 weeks), in addition to the high dose intravenous administration (400 mg/kg/4 weeks) of γ-gl. Because of the poor prognosis of patients with CEMA, the intraventricular administration of γ-gl should be initiated immediately following a diagnosis of enteroviral meningitis.

    Scopus

    PubMed

    researchmap

  • Pick's disease: selective occurrence of apolipoprotein E-immunoreactive Pick bodies in the limbic system Reviewed

    S Hayashi, K Wakabayashi, K Iwanaga, A Kakita, K Seki, M Tanaka, K Okuizumi, O Onodera, H Tanaka, S Tsuji, H Takahashi

    ACTA NEUROPATHOLOGICA   95 ( 1 )   1 - 4   1998.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER VERLAG  

    We carried out immunohistochemical examination of apolipoprotein E (apoE) in brains from two patients with Pick's disease. In these cases 1 and 2, the APOE genotypes were epsilon 3/4 and epsilon 3/3, respectively. In both cases, numerous argyrophilic globular intraneuronal inclusions, Pick bodies (PBs), were distributed widely throughout the brain, and immunohistochemically were occasionally positive for apoE. Interestingly, such apoE-immunoreactive PBs were virtually restricted to neurons in the limbic system; in the dentate gyrus, the proportion of apoE-immunoreactive PBs relative to the total number of argyrophilic PBs was 5.0% in case 1 and 2.7% in case 2, whereas in the frontal and temporal neocortices it was less than 0.1% in both cases. Diffuse cytoplasmic immunoreactivity for apoE was found in only a few limbic system neurons without PBs in both cases. In conclusion, it is considered that apoE may not be positively involved in the process of PB formation and that the preferential distribution of apoE-immunoreactive PBs in the limbic system may reflect the presence of certain regional factors associated with the synthesis or metabolism of apoE in this particular system.

    DOI: 10.1007/s004010050759

    Web of Science

    PubMed

    researchmap

  • Inhibition of alpha-ketoglutarate- and pyruvate dehydrogenase complexes in E-coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions? Reviewed

    AJL Cooper, KFR Sheu, Burke, JR, O Onodera, WJ Strittmatter, AD Roses, JP Blass

    AGE   21 ( 1 )   25 - 30   1998.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER AGING ASSOC  

    At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Q(n)) in the proteins expressed by the affected genes. Generally, n greater than or equal to 40 in affected individuals and less than or equal to 36 in clinically unaffected individuals. The expansion has been proposed to confer a "toxic gain of function" to the mutated protein. Poly-Q domains have recently been shown to be excellent substrates of tissue transglutaminase. We investigated the effects of expression of glutathione S-transferase constructs containing poly-Q inserts of various lengths (GSTQ(n) where n = 0, 10, 62 or 81) on the activity of some key metabolic enzymes in the host Escherischia coli - an organism not known to have transglutaminase activity. E. coli carrying the GSTQ(62) construct exhibited statistically significant decreases in the specific activities of oc-ketoglutarate dehydrogenase complex (KGDHC) and pyruvate dehydrogenase complex (PDHC). Previous work has shown that KGDHC and PDHC activities are reduced in the brains of Alzheimer's disease (AD) patients. Our results suggest that KGDHC and PDHC may be particularly susceptible to the effects of a number of disparate insults, including those associated with AD and HD.

    DOI: 10.1007/s11357-998-0004-x

    Web of Science

    PubMed

    researchmap

  • Prevertebral abscesses with a protracted insidious clinical course and subsequent lethal, acute pyogenic meningitis and septic shock Reviewed

    Tetsutaro Ozawa, Osamu Onodera, Akiyoshi Kakita, Kenju Aoki, Keiko Tanaka, Yoshiaki Soma, Hitoshi Takahashi, Shoji Tsuji

    Brain and Nerve   50 ( 1 )   75 - 79   1998.1

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    This report concerns a 66-year-old man suffering from prevertebral abscesses with a protracted insidious clinical course and subsequent lethal and acute pyogenic meningitis. The patient had a three-month history of mild neck pain, and died as a result of septic shock due to staphylococcus aureus (methicillin-susceptible) infection two days after admission to the hospital. At autopsy, abscesses encapsulated by fibrous connective tissue were found on the ventral surfaces of the cervical and thoracic regions of the spine. The prevertebral abscess on the upper cervical region was organized with dense fibrous tissue and contained a small number of inflammatory cells. On the other hand, the prevertebral abscess on the thoracic region was purulent and contained numerous inflammatory cells, macrophages and gram-positive cocci. Pyogenic spondylitis and discitis accompanying the prevertebral abscesses were multiple and widespread. These features suggested that the abscesses developed initially on the cervical region, extended caudally through the prevertebral space, directly involving the corpus vertebrae and discs, and ultimately caused sepsis. It is important to note that prevertebral abscesses can exhibit a protracted clinical course with only mild symptom such as minor neck pain and then manifest abruptly as acute meningitis and sepsis.

    Scopus

    PubMed

    researchmap

  • Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy - Influence of CAG repeat size on MRI findings Reviewed

    R Koide, O Onodera, T Ikeuchi, R Kondo, H Tanaka, S Tokiguchi, A Tomoda, T Miike, F Isa, H Beppu, N Shimizu, Y Watanabe, Y Horikawa, T Shimohata, K Hirota, A Ishikawa, S Tsuji

    NEUROLOGY   49 ( 6 )   1605 - 1612   1997.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units greater than or equal to 66; group 2, number of CAG repeat units less than or equal to 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group I) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

    Web of Science

    PubMed

    researchmap

  • Transglutaminase-catalyzed inactivation of glyceraldehyde 3-phosphate dehydrogenase and alpha-ketoglutarate dehydrogenase complex by polyglutamine domains of pathological length Reviewed

    AJL Cooper, KFR Sheu, Burke, JR, O Onodera, WJ Stritmatter, AD Roses, JP Blass

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   94 ( 23 )   12604 - 12609   1997.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

    Several adult-onset neurodegenerative diseases are caused by genes with expanded CAG triplet repeats within their coding regions and extended polyglutamine (a) domains within the expressed proteins. Generally, in clinically affected individuals n greater than or equal to 40. Glyceraldehyde 3-phosphate dehydrogenase binds tightly to four Q(n) disease proteins, but the significance of this interaction is unknown. We now report that purified glyceraldehyde 3-phosphate dehydrogenase is inactivated by tissue transglutaminase in the presence of glutathione S-transferase constructs containing a a domain of pathological length (n = 62 or 81). The dehydrogenase is less strongly inhibited by tissue transglutaminase in the presence of constructs containing shorter Q(n) domains (n = 0 or 10). Purified cr-ketoglutarate dehydrogenase complex also is inactivated by tissue transglutaminase plus glutathione S-transferase constructs containing pathological-length a domains (n = 62 or 81). The results suggest that tissue transglutaminase-catalyzed covalent linkages involving the larger poly-Q domains may disrupt cerebral energy metabolism in CAG/Q(n) expansion diseases.

    DOI: 10.1073/pnas.94.23.12604

    Web of Science

    PubMed

    researchmap

  • Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells Reviewed

    O Onodera, Burke, JR, SE Miller, S Hester, S Tsuji, AD Roses, WJ Strittmatter

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   238 ( 2 )   599 - 605   1997.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    Six inherited neurologic diseases, including Huntington's disease, result from the expansion of a CAG domain of the disease genes to produce a domain of more than 40 glutamines in the expressed protein. The mechanism by which expansion of this polyglutamine domain causes disease is unknown. Recent studies demonstrated oligomerization of polyglutamine-domain proteins in mammalian neurons. To study oligomerization of polyglutamine proteins and to identify heterologous protein interactions, varying length polyglutamine-green fluorescent protein fusion proteins were expressed in cultured COS-7 cells. The 19- and 35-glutamine fusion proteins (non-pathologic length) distributed diffusely throughout the cytoplasm. In contrast, 56- and 80-glutamine fusion proteins (pathologic length) formed fibrillar arrays resembling those previously observed in neurons in Huntington's disease and in a transgenic mouse model. These aggregates were intranuclear and intracytoplasmic. Intracytoplasmic aggregates were surrounded by collapsed intermediate filaments, The intermediate filament protein vimentin co-immunoisolated with expanded polyglutamine fusion proteins. This cellular model will expedite investigations into oligomerization of polyglutamine proteins and their interactions with other proteins. (C) 1997 Academic Press.

    DOI: 10.1006/bbrc.1997.7337

    Web of Science

    PubMed

    researchmap

  • Polyglutamine domains are substrates of tissue transglutaminase: Does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases? Reviewed

    AJL Cooper, KFR Sheu, Burke, JR, O Onodera, WJ Strittmatter, AD Roses, JP Blass

    JOURNAL OF NEUROCHEMISTRY   69 ( 1 )   431 - 434   1997.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT-RAVEN PUBL  

    Huntington's disease and six other neurodegenerative diseases are associated with abnormal gene products containing expanded polyglutamine (poly-Q; Q(n)) domains (n &gt; 40). in the present work, we show that glutathione S-transferase (GST) fusion proteins containing a small, physiological-length poly-Q domain (GSTQ(10)) or a large, pathological-length poly-Q domain (GSTQ(62)) are excellent substrates of guinea pig liver (tissue) transglutaminase and that both GSTQ(10) and GSTQ(62) are activators of tissue transglutaminase-catalyzed hydroxaminolysis of N-alpha-carbobenzoxyglutaminylglycine. The present findings have implications for understanding the pathophysiological mechanisms of expanded CAG/poly-Q domain diseases.

    DOI: 10.1046/j.1471-4159.1997.69010431.x

    Web of Science

    PubMed

    researchmap

  • Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy (DRPLA) cDNA: Strong conservation of a polymorphic CAG repeat in the murine gene Reviewed

    M Oyake, O Onodera, T Shiroishi, H Takano, Y Takahashi, R Kominami, K Moriwaki, T Ikeuchi, S Igarashi, H Tanaka, S Tsuji

    GENOMICS   40 ( 1 )   205 - 207   1997.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    DOI: 10.1006/geno.1996.4522

    Web of Science

    PubMed

    researchmap

  • Changes in anti-HuD antibody titers in the long-term course in paraneoplastic sensory neuropathy Reviewed

    Y Yagi, T Inuzuka, K Takada, R Nakano, Hozumi, I, H Yoshimoto, O Onodera, K Tanaka, S Sato, M Takahashi

    EUROPEAN NEUROLOGY   37 ( 2 )   122 - 123   1997

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:KARGER  

    DOI: 10.1159/000117422

    Web of Science

    PubMed

    researchmap

  • Toxicity of expanded polyglutamine-domain proteins in Escherichia coli Reviewed

    O Onodera, AD Roses, S Tsuji, JM Vance, WJ Strittmatter, Burke, JR

    FEBS LETTERS   399 ( 1-2 )   135 - 139   1996.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that long polyglutamine domains (59-81 residues) as GST-fusion proteins inhibit growth while smaller glutamine (10-35 residues) or polyalanine (61 residues) domains have no effect. Analogously in humans, polyglutamine repeats less than 35-40 glutamines produce a normal phenotype, while expansion greater than 40 glutamines is always associated with disease. Expression of polyglutamine proteins in E. coli may help identify the molecular mechanism of pathogenesis of CAG trinucleotide repeat diseases and be a useful screen to identify potential therapeutic compounds.

    DOI: 10.1016/S0014-5793(96)01301-4

    Web of Science

    PubMed

    researchmap

  • Lack of association of very low density lipoprotein receptor gene polymorphism with Caucasian Alzheimer's disease Reviewed

    K Okuizumi, O Onodera, K Seki, H Tanaka, Y Namba, K Ikeda, AM Saunders, MA PericakVance, AD Roses, S Tsuji

    ANNALS OF NEUROLOGY   40 ( 2 )   251 - 254   1996.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LITTLE BROWN CO  

    To determine whether the association of the very low density lipoprotein receptor (VLDL-R) gene with Alzheimer's disease (AD), which has recently been identified in Japanese AD patients, is commonly observed in AD patients of other ethnic backgrounds, we have investigated the allele frequency of the polymorphic CGG repeat in the 5'-UTR of the VLDL-R gene using a data set of 84 caucasian AD patients with 104 caucasian controls. Although the allele frequency of the 8-repeat allele was slightly lower, and that of 9-repeat allele was slightly higher, in the caucasian AD patients than in caucasian controls, the differences were not statistically significant. Multiple logistic regression analysis using apolipoprotein E4 (APOE4) allele, 5-, 8-, or 9-repeat allele of the VLDL-R gene, sex, and age at onset as the predictors revealed that only the APOE4 allele was significantly associated with AD in the data set of the caucasian AD patients and controls.

    DOI: 10.1002/ana.410400220

    Web of Science

    PubMed

    researchmap

  • Association study between schizophrenia and dopamine D3 receptor gene polymorphism Reviewed

    T Tanaka, S Igarashi, O Onodera, H Tanaka, M Takahashi, M Maeda, K Kameda, S Tsuji, S Ihda

    AMERICAN JOURNAL OF MEDICAL GENETICS   67 ( 4 )   366 - 368   1996.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Crocq et al, [1992: J Med Genet 29:858-860] reported the existence of an association between schizophrenia and homozygosity of a Ball polymorphism in the first exon of the dopamine D3 receptor (DRD3) gene, In response to this report, further studies were conducted; however, these studies yielded conflicting results, In the present study, we examined 100 unrelated Japanese schizophrenics and 100 normal controls to determine any association between this polymorphism and schizophrenia, Results suggest that neither allele nor genotype frequencies of the DRD3 gene in the schizophrenics as a whole are significantly different from those of the controls, Further, we found no association between any allele or genotype and any clinical subtype based on family history of schizophrenia and age-at-onset, A significantly high frequency of homozygosity of a dopamine D3 receptor gene allele was not observed in the schizophrenics as a whole, or in clinical subtypes, Our results suggest that an association between the dopamine D3 receptor gene and schizophrenia is unlikely to exist. (C) 1996 Wiley-Liss, Inc.

    DOI: 10.1002/(SICI)1096-8628(19960726)67:4<366::AID-AJMG9>3.0.CO;2-K

    Web of Science

    PubMed

    researchmap

  • Non-Mendelian transmission in Dentatorubral-Pallidoluysian atrophy and Machado-Joseph disease: The mutant allele is preferentially transmitted in male meiosis Reviewed

    T Ikeuchi, S Igarashi, Y Takiyama, O Onodera, M Oyake, H Takano, R Koide, H Tanaka, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   58 ( 4 )   730 - 733   1996.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:UNIV CHICAGO PRESS  

    Autosomal dominant dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) are neurodegenerative disorders caused by CAG trinucleotide repeat expansions. An inverse correlation of age at onset with the length of the expanded CAG trinucleotide repeats has been demonstrated, and the intergenerational instability of the length of the CAG trinucleotide repeats, which is more prominent in paternal than in maternal transmissions, has been shown to underlie the basic mechanisms of anticipation in DRPLA and MJD. Our previous observations on DRPLA and MJD pedigrees, as well as a review of the literature, have suggested that the numbers of affected offspring exceed those of unaffected offspring, which is difficult to explain by the Mendelian principle of random segregation of alleles. In the present study, we analyzed the segregation patterns in 211 transmissions in 24 DRPLA pedigrees and 80 transmissions in 7 MJD pedigrees, with the diagnoses confirmed by molecular testing. Significant distortions in favor of transmission of the mutant alleles were found in male meiosis, where the mutant alleles were transmitted to 62% of all offspring in DRPLA (chi(2) = 7.69; P &lt; .01) and 73% in MJD (chi(2) = 6.82; P &lt; .01). The results were consistent with meiotic drive in DRPLA and MJD. Since more prominent meiotic instability of the length of the CAG trinucleotide repeats is observed in male meiosis than in female meiosis and meiotic drive is observed only in male meiosis, these results raise the possibility that a common molecular mechanism underlies the meiotic drive and the meiotic instability in male meiosis.

    Web of Science

    PubMed

    researchmap

  • Lack of association between dopamine D2 receptor gene Cys311 variant and schizophrenia Reviewed

    T Tanaka, S Igarashi, O Onodera, H Tanaka, N Fukushima, M Takahashi, K Kameda, S Tsuji, S Ihda

    AMERICAN JOURNAL OF MEDICAL GENETICS   67 ( 2 )   208 - 211   1996.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Itokawa et al, [1993] reported identifying one missense nucleotide mutation from C to G resulting in a substitution of serine with cysteine at codon 311 in the third intracellular loop of the dopamine D2 receptor in schizophrenics, Arinami et al, [1994] reported finding a positive association between the Cys311 variant and schizophrenia. In response to the report by Arinami et al, [1994] we examined 106 unrelated Japanese schizophrenics and 106 normal controls to determine if there is any association of the Cys311 variant with schizophrenia. However, we found no statistically significant differences in allelic frequencies of Cys311 between schizophrenia and normal controls. The present results as well as those of all previous studies except for that of Arinami et al. [1994] indicated that an association between the dopamine D2 receptor gene and schizophrenia is unlikely to exist. (C) 1996 Wiley-Liss, Inc.

    DOI: 10.1002/(SICI)1096-8628(19960409)67:2<208::AID-AJMG12>3.0.CO;2-N

    Web of Science

    PubMed

    researchmap

  • Molecular cloning of murine homologue cdna for dentatorubral-pallidoluysian atrophy (DRPLA) gene

    Oyake, M., Onodera, O., Shiroishi, T., Takano, H., Igarashi, S., Tanaka, H., Moriwaki, K., Tsuji, S.

    Japanese Journal of Human Genetics   41 ( 1 )   91 - 91   1996

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    researchmap

  • Somatic mosaicism of CAG repeat expansion could be associated with brain shrinkage in DRPLA

    Takano, H., Onodera, O., Takahashi, H., Yamada, M., Igarashi, S., Oyakei, M., Ikeuchii, T., Koide, R., Tanaka, H., Iwabuchi, K., Tsuji, S.

    Japanese Journal of Human Genetics   41 ( 1 )   33 - 33   1996

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    researchmap

  • Lack of association between dopamine D4 receptor gene and schizophrenia Reviewed

    T Tanaka, S Igarashi, O Onodera, H Tanaka, K Kameda, K Takahashi, S Tsuji, S Ihda

    AMERICAN JOURNAL OF MEDICAL GENETICS   60 ( 6 )   580 - 582   1995.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    An intriguing property of the dopamine D4 receptor gene is a hypervariable segment in the coding region characterized by a varying number of direct imperfect 48 bp repeats (2-8 or 10 repeats) in the third exon of he gene [Lichter et al., 1993: Hum Mol Genet 2:767-773]. The authors analyzed 70 unrelated schizophrenics and 70 normal controls to determine the allele and genotype frequencies created by length polymorphism of dopamine D4 receptor gene. All patients and controls were unrelated and from the Japanese population. Patients were divided into three groups with regard to age at onset, familial loading, and severity of symptoms assessed strictly with Manchester scale. There were no statistically significant differences if the distributions of alleles and genotypes were analyzed for schizophrenia as a whole or analyzed in consideration of those clinical subtypes, Lichter and colleagues [1993] have reported that at least 25 haplotypes exist for this polymorphic region of the. dopamine receptor D4 gene, In this study only the alleles created by length polymorphism were analyzed, and further investigation to determine the haplotypes of patients and controls on using a much larger sample size will be required. (C) 1995 Wiley-Liss, Inc.

    DOI: 10.1002/ajmg.1320600620

    Web of Science

    PubMed

    researchmap

  • DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY - CLINICAL-FEATURES ARE CLOSELY-RELATED TO UNSTABLE EXPANSIONS OF TRINUCLEOTIDE (CAG) REPEAT Reviewed

    T IKEUCHI, R KOIDE, H TANAKA, O ONODERA, S IGARASHI, H TAKAHASHI, R KONDO, A ISHIKAWA, A TOMODA, T MIIKE, K SATO, Y IHARA, T HAYABARA, F ISA, H TANABE, S TOKIGUCHI, M HAYASHI, N SHIMIZU, F IKUTA, H NAITO, S TSUJI

    ANNALS OF NEUROLOGY   37 ( 6 )   769 - 775   1995.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LITTLE BROWN CO  

    Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat affects the clinical manifestations of dentatorubral-pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = -0.696, p &lt; 0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62-79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non-progressive myoclonus epilepsy phenotype showed smaller expansions (54-67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral-pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral-pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

    DOI: 10.1002/ana.410370610

    Web of Science

    PubMed

    researchmap

  • TRIAL TO ESTABLISH AN ANIMAL-MODEL OF PARANEOPLASTIC CEREBELLAR DEGENERATION WITH ANTI-YO ANTIBODY .1. MOUSE STRAINS BEARING DIFFERENT MHC MOLECULES PRODUCE ANTIBODIES ON IMMUNIZATION WITH RECOMBINANT YO PROTEIN, BUT DO NOT CAUSE PURKINJE-CELL LOSS Reviewed

    M TANAKA, K TANAKA, O ONODERA, S TSUJI

    CLINICAL NEUROLOGY AND NEUROSURGERY   97 ( 1 )   95 - 100   1995.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:VAN GORCUM CO BV  

    Passive transfer of anti-Yo antibody from patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecological or breast carcinoma has not been successful in inducing an animal model. We used active immunization with recombinant Yo protein of four strains of mice bearing different MHC molecules: BALB/c (H-2d), C3H (H-2k), C57BL/6 (H-2b), SJL/J (H-2s). All the strains produced high anti-Yo antibody titer but none developed cerebellar ataxia or showed Purkinje cell loss. Spleen cells from the immunized mice also reacted with recombinant protein. Because C57BL/6(nu/nu) mice produce no anti-Yo antibody, mature helper T cells are required for its production. Results suggest that antibody production in peripheral blood alone is not sufficient for the development of PCD and that MHC class II molecules function in the activation of T cells to help B cells produce antibodies.

    Web of Science

    PubMed

    researchmap

  • TRIAL TO ESTABLISH AN ANIMAL-MODEL OF PARANEOPLASTIC CEREBELLAR DEGENERATION WITH ANTI-YO ANTIBODY .2. PASSIVE TRANSFER OF MURINE MONONUCLEAR-CELLS ACTIVATED WITH RECOMBINANT YO PROTEIN TO PARANEOPLASTIC CEREBELLAR DEGENERATION LYMPHOCYTES IN SEVERE COMBINED IMMUNODEFICIENCY MICE Reviewed

    K TANAKA, M TANAKA, S IGARASHI, O ONODERA, T MIYATAKE, S TSUJI

    CLINICAL NEUROLOGY AND NEUROSURGERY   97 ( 1 )   101 - 105   1995.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:VAN GORCUM CO BV  

    Passive transfer of serum IgG or mononuclear cells from peripheral blood of a patient with paraneoplastic cerebellar degeneration (PCD) to rodents was carried out in order to examine the role of anti-Purkinje cell antibody (anti-Yo antibody) present in serum and cerebrospinal fluid of PCD patients. After a single injection of IgG into mouse brain, it was taken up by Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells into rat ventricles did not cause Purkinje cell loss. We also studied passive transfer of the PCD patient's lymphocytes to mice with severe combined immunodeficiency (SCID). We constructed a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody for immunizing mice, and that resulted in production of significant amounts of anti-Yo antibody. Spleen cells from these Yo protein immunized mice were injected intravenously or intracerebrally into naive mice that subsequently showed no neurological symptoms or loss of Purkinje cells. We conclude that the anti-Yo antibody, either in combination with or without complement or activated mononuclear cells, cannot be the sole cause of Purkinje cell loss.

    Web of Science

    PubMed

    researchmap

  • DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) - CLOSE CORRELATION OF CAG REPEAT EXPANSIONS WITH THE WIDE SPECTRUM OF CLINICAL PRESENTATIONS AND PROMINENT ANTICIPATION Reviewed

    T IKEUCHI, O ONODERA, M OYAKE, R KOIDE, H TANAKA, S TSUJI

    SEMINARS IN CELL BIOLOGY   6 ( 1 )   37 - 44   1995.2

     More details

    Language:English   Publisher:ACADEMIC PRESS (LONDON) LTD  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy and dementia as well as various ages of onset. We have identified a specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 as the pathogenic mutation for DRPLA. We investigated how the degree of the expansion of the CAG repeat affects the clinical manifestations of DRPLA. The sires of the expanded alleles were well correlated with the ages of onset (r = -0.6955, P&lt;0.001). Patients with progressive myoclonus epilepsy (PME) phenotype had larger expansions (62-79 repeats) and earlier ages of onset (onset before age 20). Furthermore, most of the patients with PME phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with non-PME phenotype showed later ages of onset (onset after age 20) and smaller expansions (54-67 repeats). When ages of onset of each clinical symptom are compared with sizes of the CAG repeat, there is again a remarkably high correlation of the sizes of CAG repeat with each of the clinical symptoms. Thus the wide variation in clinical manifestations of DRPLA can now be clearly explained based on-the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

    Web of Science

    PubMed

    researchmap

  • LONG-TERM COURSE OF CHANGE IN ANTI-YO ANTIBODY CONTENT IN PARANEOPLASTIC CEREBELLAR DEGENERATION Reviewed

    K TANAKA, M TANAKA, S IGARASHI, O ONODERA, T NAKAJIMA, M YAMAZAKI, T MIYATAKE, S TSUJI

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   58 ( 2 )   256 - 257   1995.2

     More details

    Language:English   Publisher:BRITISH MED JOURNAL PUBL GROUP  

    Web of Science

    PubMed

    researchmap

  • Auditory comprehension in transcortical motor aphasia due to a medial lesions of the left frontal lobe Reviewed

    M. Otsuki, Y. Soma, O. Onodera, S. Tsuji, A. Satoh, N. Yamada

    Brain and Nerve   47 ( 11 )   1081 - 1085   1995

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    We assessed the anatomical findings and auditory comprehension of six patients with transcortical motor aphasia due to medial lesions of the left frontal lobe. All patients were right handed and were initially mute for several hours after the onset, and they exhibited mild paresis of the right lower extremity. Their spontaneous speech was sparse and not fluent, and sometimes accompanied by echolalia, but their articulation was normal and repetition was excellent. They had difficulty in recalling words. A diagnosis of transcortical motor aphasia was made on the basis of their clinical symptoms. All patients were found to have an infarct in the left medial frontal region by MRI and/or CT. We administered the Western Aphasia Battery and 50 line drawing pointing task in order to evaluate auditory comprehension. Based on the results we concluded that there is no impairment of auditory comprehension of single words when lesions are limited to the superior frontal gyrus, but that lesions extending to the middle frontal gyrus interfere with auditory comprehension of single words. Our observations indicate that the middle frontal gyrus plays an important role in auditory comprehension of single words. All of the patients displayed impaired auditory comprehension of sentences even when their lesions were strictly limited to the medial frontal lobe. This suggests that the medial frontal lobe plays some role in the auditory comprehension of sentences.

    Scopus

    PubMed

    researchmap

  • Trial to establish an animal model of paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibody 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to naive SJL or PCD lympphocytes to severe combined immunodefic Reviewed

    Tanaka K, Tanaka M, Igarashi S, Onodera O, Miyatake T, Tsuji S

    Clin Neurol Neurosurg   97   101 - 105   1995

     More details

    Language:English  

    researchmap

  • Paraneoplastic cerebellar degeneration - Characterization of anti-yo antibody and underlying cancer Reviewed

    K. Tanaka, M. Tanaka, O. Onodera, S. Tsuji

    Clinical Neurology   35 ( 7 )   770 - 774   1995

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A group of patients with paraneoplastic cerebellar degeneration (PCD) have shown to produce auto-antibody to both neurons and tumor cells (anti-Yo antibody). More than 60% of these patients have shown neurological symptoms and anti-Yo antibody production before the underlying cancers were found, which suggests that the test for anti-Yo antibody is important for the early detection and treatment of cancer. Originally, anti-Yo antibody has been characterized as 1)labelling the cytoplasm of cerebellar Purkinje cells immunohistochemically, 2)binding to the 62 and 34kDa bands on immunoblots of Purkinje cell extracts, 3) being present in female patients with gynecological or breast cancers. Recently, the common binding-epitope of anti-Yo antibody has been reported as leucine-zipper protein. In order to detect the anti-Yo antibody precisely, we examined the immunohistochemical and western blot characters of the recombinant leucine-zipper protein- reactive (anti-Yo) antibody. The results were, 1)sera containing leucine- zipper protein-reactive antibody labels both cerebellar Purkinje cells but some sera might contain other antibodies together with anti-Yo that confuse the immunostaining character of anti-Yo antibody, 2)the antibody binds to 58 kDa band and sometimes co-binds to 34kDa on immunoblots of cerebellar tissue extracts. The underlying cancers are mainly adenocarcinoma in the ovary, fallopian tube, uterus, or breast but occasionally large cell lung and bile duct cancers have been found. Interestingly, a male patient had an antibody similar in character to be anti-Yo antibody immunohistochemically and on immunoblots, that did not recognize leucine-zipper protein and the underlying carcinoma was small cell lung cancer. These results suggest that 1) the diagnosis of anti-Yo antibody should be based on the antibody's reactivity with leucine-zipper protein, 2) some sera with the anti-Yo antibody label other tissues besides the Purkinje cell cytoplasm because of the co-existance of other antibodies seen immunohistochemically and on immunoblots, 3) the search for underlying cancers should not be limited to gynecological or breast carcinomas.

    Scopus

    PubMed

    researchmap

  • Lack of association between dopamine D4 receptor gene and schizophrenia Reviewed

    T. Tanaka, S. Igarashi, O. Onodera, H. Tanaka, K. Kameda, K. Takahashi, S. Tsuji, S. Ihda

    American Journal of Medical Genetics - Neuropsychiatric Genetics   60 ( 6 )   580 - 582   1995

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    An intriguing property of the dopamine D4 receptor gene is a hypervariable segment in the coding region characterized by a varying number of direct imperfect 48 bp repeats (2-8 or 10 repeats) in the third exon of the gene [Lichter et al., 1993: Hum Mol Genet 2:767-773]. The authors analyzed 70 unrelated schizophrenics and 70 normal controls to determine the allele and genotype frequencies created by length polymorphism of dopamine D4 receptor gene. All patients and controls were unrelated and from the Japanese population. Patients were divided into three groups with regard to age at onset, familial loading, and severity of symptoms assessed strictly with Manchester scale. There were no statistically significant differences if the distributions of alleles and genotypes were analyzed for schizophrenia as a whole or analyzed in consideration of those clinical subtypes. Lichter and colleagues [1993] have reported that at least 25 haplotypes exist for this polymorphic region of the dopamine receptor D4 gene. In this study only the alleles created by length polymorphism were analyzed, and further investigation to determine the haplotypes of patients and controls on using a much larger sample size will be required.

    DOI: 10.1002/ajmg.1320600620

    Scopus

    PubMed

    researchmap

  • PARTIAL DELETIONS OF PUTATIVE ADRENOLEUKODYSTROPHY (ALD) GENE IN JAPANESE ALD PATIENTS Reviewed

    R KOIKE, O ONODERA, H TABE, K KANEKO, T MIYATAKE, S IWASAKI, M NAKANO, N SHIZUMA, K IKEGUCHI, M NISHIZAWA, J MOSSER, CO SARDE, S TSUJI

    HUMAN MUTATION   6 ( 3 )   263 - 267   1995

     More details

    Language:English   Publisher:WILEY-LISS  

    DOI: 10.1002/humu.1380060314

    Web of Science

    PubMed

    researchmap

  • DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) - MOLECULAR-BASIS FOR WIDE CLINICAL-FEATURES OF DRPLA Reviewed

    T IKEUCHI, R KOIDE, O ONODERA, H TANAKA, M OYAKE, H TAKANO, S TSUJI

    CLINICAL NEUROSCIENCE   3 ( 1 )   23 - 27   1995

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA. (C) 1995 Wiley-Liss, Inc.

    Web of Science

    PubMed

    researchmap

  • PASSIVE TRANSFER AND ACTIVE IMMUNIZATION WITH THE RECOMBINANT LEUCINE-ZIPPER (YO) PROTEIN AS AN ATTEMPT TO ESTABLISH AN ANIMAL-MODEL OF PARANEOPLASTIC CEREBELLAR DEGENERATION Reviewed

    K TANAKA, M TANAKA, O ONODERA, S IGARASHI, T MIYATAKE, S TSUJI

    JOURNAL OF THE NEUROLOGICAL SCIENCES   127 ( 2 )   153 - 158   1994.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Passive transfer of paraneoplastic cerebellar degeneration (PCD) IgG to rodents as well as active immunization with recombinant Yo fusion protein were tried in order to examine the roles of anti-Purkinje cell antibody (anti-Yo antibody) present in the sera and cerebrospinal fluid of patients with PCD in Purkinje cell loss, the hall mark of PCD pathology. On a single injection of PCD IgG to mouse brain, IgG was taken into Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells to rats ventricles did not cause Purkinje cell loss. We made a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody. Mice immunized with this Yo protein produced high titer antibody against it for more than 3 months, during which time neither neurological symptoms nor Purkinje cell loss occurred. The anti-Yo antibody, with or without complement or activated mononuclear cells, therefore could not be the sole cause of Purkinje cell loss.

    Web of Science

    PubMed

    researchmap

  • TRINUCLEOTIDE REPEAT LENGTH AND RATE OF PROGRESSION OF HUNTINGTONS-DISEASE Reviewed

    SN ILLARIOSHKIN, S IGARASHI, O ONODERA, ED MARKOVA, NN NIKOLSKAYA, H TANAKA, TZ CHABRASHWILI, NG INSAROVA, K ENDO, IA IVANOVASMOLENSKAYA, S TSUJI

    ANNALS OF NEUROLOGY   36 ( 4 )   630 - 635   1994.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LITTLE BROWN CO  

    The Huntington's disease gene contains an expanded unstable (CAG)(n) repeat, and the repeat lengths have been shown to correlate with the age of onset. Using detailed clinical scales, we evaluated the rate of progression of Huntington's disease and its relationship to the number of triplet repeats. We found significant positive correlation between the rate of progression of clinical symptoms (both neurological and psychiatric) and CAG repeat length. These data suggest an important role of expanded trinucleotide repeat length in affecting the pathological process during the entire course of Huntington's disease.

    DOI: 10.1002/ana.410360412

    Web of Science

    PubMed

    researchmap

  • APOE-EPSILON-4 AND EARLY-ONSET ALZHEIMERS Reviewed

    K OKUIZUMI, O ONODERA, H TANAKA, H KOBAYASHI, S TSUJI, H TAKAHASHI, K OYANAGI, K SEKI, M TANAKA, S NARUSE, T MIYATAKE, H MIZUSAWA, KANAZAWA, I

    NATURE GENETICS   7 ( 1 )   10 - 11   1994.5

     More details

    Language:English   Publisher:NATURE PUBLISHING CO  

    DOI: 10.1038/ng0594-10b

    Web of Science

    PubMed

    researchmap

  • The detection of anti-Purkinje cell antibody (anti-Yo antibody) by ELISA using recombinant Yo fusion protein Reviewed

    K. Tanaka, M. Tanaka, O. Onodera, S. Igarashi, S. Tsuji

    Brain and Nerve   46 ( 1 )   47 - 51   1994

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Paraneoplastic cerebellar degeneration (PCD) is a remote effect of cancer mediated by possibly immunological mechanisms. The sera and cerebrospinal fluid of PCD patients containing high titer autoantibody against cerebellar Purkinje cells had been reported. This antibody binds to 62-kD and 34-kD bands of cerebellar Purkinje cell homogenates (anti-Yo antibody). However, it is not always true that the autoantibody of this character on immunoblot and immunohistochemistry recognizes the same molecule. Recently, the DNA sequence encoding the Yo antigen, whose common epitope is a sequence containing leucine-zipper motif, was reported. We made the recombinant protein deduced from the cDNA clone encoding the leucine-zipper motif of the Yo antigen. Using this recombinant protein as the antigen for ELISA, the anti Yo antibodies in the sera and CSF were examined and 3 new patients with PCD possesing anti-Yo antibody were found. The sera of one patient, serially taken during several kinds of treatment were examined with this ELISA system, which revealed that the anti-Yo antibody titer was increased after plasmapheresis and reduced after tumor resection and anti-cancer chemotherapy. The early resection of malignant tumors may prevent the continuous production of high titer anti-Yo antibody and stop the progression of cerebellar tissue damage.

    Scopus

    PubMed

    researchmap

  • Correlation between degrees of the CTG repeat expansion and clinical features of myotonic dystrophy Reviewed

    I. Eguchi, R. Koike, O. Onodera, K. Tanaka, H. Kondo, S. Tsuji

    Clinical Neurology   34 ( 2 )   118 - 123   1994

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    The mutation in myotonic dystrophy gene has recently been identified as an unstable expanison of trinucleotide CTG repeat located at the 3'-untranslated region of myotoninprotein kinase gene. In this paper we report the correlation between the degree of CTG amplification and clinical features in 35 individuals with myotonic dystrophy. The analysis of CTG repeat expansion was performed with Southern blot hybridization. Genomic DNA from peripheral blood leukocytes was digested with a restriction endonuclease, Pst I, instead of commonly used EcoRI. Since small expansion (about 190 bp) could be detected with PstI digestion and furthermore, the DNA fragment did not contain insertion/deletion polymorphism, we were able to accurately determine the exact sizes of CTG repeat expansion. We have observed a tendency of earlier ages of onset with larger allele sizes. The good correlation between the size of the expansion and the severity in muscle weakness was clearly demonstrated especially if the analysis was focused on the patients at same age group at 40~45 years. The severity of motor disability was classified into three stages. The mean size of expansion was 0.33 ± 0.17 (M ± SD) kbp in stage I, 2.58 ± 1.42 kbp in stage II, and 4.75 ± 0.93 kbp in stage III. The tendency was also observed when patients were categorized according to the intellectual grade. The anticipation was observed in all the parent-child pairs. When the increases of the repeat expansions were compared between father-child and mother-child transmissions, broader variation of the increases was observed in father-child transmissions. Our study indicates that Southern blot hybridization analysis of leukocyte genomic DNA was effective for the evaluation of muscle weakness and mental deficiency based on the sizes of the expanded allele.

    Scopus

    PubMed

    researchmap

  • MRI findings of posterior spinal artery syndrome - Report of a case Reviewed

    K. Okuizumi, M. Wakasugi, O. Onodera, H. Okumura, S. Tsuji

    Clinical Neurology   34 ( 11 )   1116 - 1120   1994

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A 58-year-old woman presented with sudden onset of numbness and weakness of the lower limbs. She showed paraparesis associated with hyperreflexia and pathological reflexes in lower limbs. She showed decreased sensation of vibration and proprioception in lower limbs, as well as tingling sensation below Th11 level. Pinprick and thermal sensations were spared. Magnetic resonance imaging (MRI) of the spinal cord revealed a symmetric high signal intensity area at the posterior medial part of the spinal cord spanning Th9 to Th11 on T2-weighted and proton density images. On the basis of clinical findings as well as MRI findings, we made a diagnosis of posterior spinal artery syndrome. The MRI findings are considered to be highly useful for the diagnosis of PSAS.

    Scopus

    PubMed

    researchmap

  • USE OF A RADIATION-REDUCED HYBRID PANEL FOR THE LOCALIZATION OF 7 MARKERS IN THE XQ28 REGION OF THE HUMAN GENOME Reviewed

    A SMAHI, B PETERLIN, O ONODERA, S TSUJI, MC FULCHIGNONILATAUD

    ANNALES DE GENETIQUE   37 ( 1 )   11 - 13   1994

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:EXPANSION SCI FRANCAISE  

    Two genes (QM and biglycan), three cDNAs expressed in the brain (TH4, TH27, p877) and two microsatellites (AFM224zg11 and AFM287ze5) are assigned in the six sub regions delimited by an IRHs panel of the human Xq28 region.

    Web of Science

    PubMed

    researchmap

  • CHROMOSOMAL LOCALIZATION OF THE EPSILON-1, EPSILON-3, AND ZETA-1 SUBUNIT GENES OF THE HUMAN NMDA RECEPTOR-CHANNEL Reviewed

    H TAKANO, O ONODERA, H TANAKA, H MORI, K SAKIMURA, T HORI, H KOBAYASHI, M MISHINA, S TSUJI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   197 ( 2 )   922 - 926   1993.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    Web of Science

    PubMed

    researchmap

  • ABSENCE OF LINKAGE DISEQUILIBRIUM AT AMYLOID PRECURSOR PROTEIN GENE LOCUS IN JAPANESE FAMILIAL ALZHEIMERS-DISEASE WITH 717VAL-]ILE MUTATION Reviewed

    H TANAKA, S NARUSE, K SEKI, O ONODERA, H KOBAYASHI, T MIYATAKE, A SHIBATA, Y SAKAKI, K KAMINO, T MIKI, N NUKINA, M IMAGAWA, NAKANO, I, T SHIMIZU, T KOJIMA, J HARDY, S TSUJI

    NEUROSCIENCE LETTERS   162 ( 1-2 )   63 - 66   1993.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCI IRELAND LTD  

    To date, eleven independent FAD pedigrees with the 717Val--&gt;Ile mutation have been identified. Interestingly, five pedigrees were of Japanese origin and four were of British origin. The apparent ethnic prediction of this mutation raises the possibility that there is a founder effect in these two island nations. We did not observe any significant linkage disequilibrium in any locus of APP and GT12 loci in the five Japanese FAD pedigrees with the 717Val--&gt;Ile mutation. A founder effect would probably not be present in Japanese FAD pedgrees with the 717Val--&gt;Ile mutation.

    Web of Science

    PubMed

    researchmap

  • Positional cloning--current status and future directions Reviewed

    Onodera, O., Tsuji, S.

    Nippon rinsho. Japanese journal of clinical medicine   51 ( 9 )   2225 - 2233   1993.9

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • Molecular genetic approach for positional cloning of X-chromosome-linked diseases Reviewed

    Onodera, O., Tanabe, H., Tuji, S., Kaneko, K., Kobayashi, H.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   38 ( 3 )   354 - 360   1993.2

     More details

    Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • HTRA1 Disorder Reviewed

    Osamu Onodera, Hiroaki Nozaki, Toshio Fukutake

    1993

     More details

    Language:English   Publisher:University of Washington, Seattle  

    CLINICAL CHARACTERISTICS: HTRA1 disorder is a phenotypic spectrum in which some individuals have few to no symptoms and others manifest with the more severe CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) phenotype. Those who have a heterozygous HTRA1 pathogenic variant may have mild neurologic findings (sometimes identified only on neuroimaging) or mild-to-moderate neurologic signs and symptoms of CARASIL. In this chapter, the term "classic CARASIL" refers to the more severe phenotype associated with biallelic pathogenic variants, and "HTRA1 cerebral small vessel disease" (HTRA1-CSVD) refers to the milder phenotype associated with a heterozygous HTRA1 pathogenic variant. Classic CARASIL is characterized by early-onset changes in the deep white matter of the brain observed on MRI, and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 40 years. Forty-four percent of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly following the onset of neurologic symptoms. Scalp alopecia and acute mid- to lower-back pain (lumbago) before age 30 years are characteristic. The most frequent initial symptom in individuals with HTRA1-CSVD is slowly progressive gait disturbance after age 40 years, which may be followed by the development of mood changes and cognitive dysfunction. A majority of affected individuals have a stroke-like episode after age 40 years. Spondylosis and alopecia are seen in a minority of individuals with HTRA1-CSVD. DIAGNOSIS/TESTING: The diagnosis of HTRA1 disorder is established in a proband by identification of either a heterozygous or biallelic pathogenic variant(s) in HTRA1 on molecular genetic testing. MANAGEMENT: Treatment of manifestations: Consideration of anti-platelet therapy and anti-hypertensive therapy for those with cerebral microbleeds; physical therapy, walking aids, and home adaptations for those with gait disturbance; consideration of medication (baclofen or tizanidine) for spasticity; wig or hairpiece for those with alopecia; standard treatment for spinal spondylosis and mood disorder; supportive care including emotional support and counseling for affected individuals and their families. Surveillance: Follow-up intervals are based on the severity and type of symptoms and the needs of the individuals and their caregivers. Agents/circumstances to avoid: Smoking and a high-salt diet, which may hasten the progression of arteriosclerosis. GENETIC COUNSELING: HTRA1 disorder caused by biallelic pathogenic variants (i.e., the classic CARASIL phenotype) is inherited in an autosomal recessive manner. HTRA1 disorder caused by heterozygous pathogenic variants is inherited in an autosomal dominant manner. Autosomal recessive inheritance. At conception, each sib of an affected individual has a 25% chance of inheriting both HTRA1 pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being heterozygous, and a 25% chance of inheriting neither pathogenic variant and not being at risk for HTRA1 disorder. Autosomal dominant inheritance. Each sib of an affected individual has a 50% risk of inheriting the pathogenic variant from their affected parent. Once the HTRA1 pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for HTRA1 disorder are possible.

    PubMed

    researchmap

  • CARASIL Reviewed

    Onodera O, Nozaki H, Fukutake T, Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A

    1993

     More details

  • Spinocerebellar Ataxia Type 17 Reviewed

    Yasuko Toyoshima, Osamu Onodera, Mitsunori Yamada, Shoji Tsuji, Hitoshi Takahashi

    1993

     More details

    Language:English   Publisher:University of Washington, Seattle  

    CLINICAL CHARACTERISTICS: Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course. DIAGNOSIS/TESTING: The diagnosis of SCA17 is established in a proband by identification of an abnormal CAG/CAA repeat expansion in TBP. Affected individuals usually have more than 41 repeats. The CAA and CAG codons both encode glutamine residues resulting in a pathogenic polyglutamine expansion. MANAGEMENT: Treatment of manifestations: Psychotropic medications for psychiatric problems, antiepileptic drugs for seizures (AEDs); botulinum toxin injections for dystonia; adaptation of the environment to accommodate dementia. Prevention of secondary complications: Side effects of psychotropic medications and AEDs may require total or intermittent discontinuation of the treatment or reduction in dose. Surveillance: Annual or semiannual evaluation by a neurologist or more frequently if symptoms are progressing rapidly. Agents/circumstances to avoid: Sedative/hypnotic agents, such as ethanol or certain medications, may exacerbate incoordination. GENETIC COUNSELING: SCA17 is inherited in an autosomal dominant manner. Offspring of affected individuals are at a 50% risk of inheriting the expanded TBP allele. The age of onset, severity, specific symptoms, and progression of the disease are variable and cannot be precisely predicted by family history or size of expansion. Prenatal testing for pregnancies at increased risk is possible if the diagnosis has been established in an affected family member by molecular genetic testing.

    PubMed

    researchmap

  • MRI findings of olivopontocerebellar atrophy and Machado-Joseph disease - Diagnostic value of transverse pontine fibers Reviewed

    J. Idezuka, O. Onodera, T. Yuasa, S. Tsuji, J. Ito

    Clinical Neurology   33 ( 3 )   289 - 293   1993

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • STRONG CORRELATION BETWEEN THE NUMBER OF CAG REPEATS IN ANDROGEN RECEPTOR GENES AND THE CLINICAL ONSET OF FEATURES OF SPINAL AND BULBAR MUSCULAR-ATROPHY Reviewed

    S IGARASHI, Y TANNO, O ONODERA, M YAMAZAKI, S SATO, A ISHIKAWA, N MIYATANI, M NAGASHIMA, Y ISHIKAWA, K SAHASHI, T IBI, T MIYATAKE, S TSUJI

    NEUROLOGY   42 ( 12 )   2300 - 2302   1992.12

     More details

    Language:English   Publisher:LIPPINCOTT-RAVEN PUBL  

    X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

    Web of Science

    PubMed

    researchmap

  • GENOMIC ORGANIZATION OF A CDNA (QM) DEMONSTRATING AN ALTERED MESSENGER-RNA LEVEL IN NONTUMORIGENIC WILMS MICROCELL HYBRID-CELLS AND ITS LOCALIZATION TO XQ28 Reviewed

    K KANEKO, H KOBAYASHI, O ONODERA, T MIYATAKE, S TSUJI

    HUMAN MOLECULAR GENETICS   1 ( 7 )   529 - 533   1992.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    Using a cosmid clone derived from human Xq28 as a probe which shows cross-species homology, we isolated cDNA clones and the nucleotide sequence analysis of the cDNA revealed that the cDNA is identical to QM cDNA. The QM cDNA has recently been reported as a cDNA with down-regulation in tumorigenic Wilms&apos; tumor microcell hybrid. Comparison of the nucleotide sequences of the cDNA with those of the genomic DNA allowed us to determine the genomic organization of the QM gene. The QM gene consists of at least 7 exons and is located at Xq28. Southern blot analysis of a somatic cell hybrid panel indicates that the QM genes are scattered at least to chromosome 2, 3, 6, 14, 16, and possibly to other chromosomes. Northern blot analysis demonstrated the QM gene is expressed in ali the examined adult human tissues as well as cell lines including HeLa cells, fibroblasts, and somatic cell hybrids with increased expression in liver, spleen, testis, and adrenal gland. The results suggest that the QM gene belongs to a new multi-gene family with yet undetermined function.

    Web of Science

    PubMed

    researchmap

  • RAPID DIAGNOSIS OF TUBERCULOUS MENINGITIS BY POLYMERASE CHAIN-REACTION (PCR) Reviewed

    K KANEKO, O ONODERA, T MIYATAKE, S TSUJI

    NEUROLOGY   40 ( 10 )   1617 - 1618   1990.10

     More details

    Language:English   Publisher:LITTLE BROWN CO  

    Web of Science

    PubMed

    researchmap

  • ATRIAL STANDSTILL AFTER TREADMILL EXERCISE TEST AND UNIQUE RESPONSE TO ISOPROTERENOL INFUSION IN RECURRENT POSTEXERCISE SYNCOPE Reviewed

    Y TAMURA, O ONODERA, K KODERA, Y IGARASHI, T MIIDA, Y AIZAWA, T IZUMI, A SHIBATA, S TAKANO

    AMERICAN JOURNAL OF CARDIOLOGY   65 ( 7 )   533 - 535   1990.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:EXCERPTA MEDICA INC  

    Web of Science

    PubMed

    researchmap

  • A case of rigid spine syndrome with rimmed vacuole Reviewed

    O. Onodera, M. Yamazaki, T. Atsumi, T. Miyatake, T. Izumi

    Clinical Neurology   30 ( 5 )   516 - 519   1990

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Scopus

    PubMed

    researchmap

  • [Research into actual conditions and preventive care in periodontal disease. Relationship between questionnaire results and periodontal disease in youth]. Reviewed

    Nakashima K, Kurihara C, Kawanaga T, Kurihashi Y, Ohsawa K, Onodera O, Shimoyama M, Watanabe Y, Ikeda K

    Nihon Shishubyo Gakkai kaishi   31 ( 4 )   1220 - 1241   1989.12

     More details

    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    The purpose of this study was to determine the prevalence of periodontal disease and the relationship between the results of questionnaire concerning periodontal disease and the actual periodontal condition in youth. The examination was carried out in three parts. In the first part, a questionnaire was conducted on 3,886 junior and senior high school students (12 to 18 years of age) living in Kawagoe, Japan. The questionnaire was composed by of items concerning habits of oral hygiene, periodontal symptoms, understanding of periodontal disease and history of diagnosis by dentist of periodontal disease. Secondary, mass intraoral examination was carried out on all objects. The examination covered gingival inflammation, periodontal probing depth, calculus, dental plaque, dental caris and malalignment. Lastly, we examined the relationship between the results of periodontal examination and questionnaire with the original periodontal classification. The following results were obtained: 1. As an example of items in questionnaire, 83.1% brushed their teeth more than two times daily. The understanding of oral hygiene concerning dental caries was improved, but concerning periodontal disease was still poor. 2. The symptom most frequently reported was gingival bleeding during tooth brushing (18.4%). 3. The percentage of persons with periodontal disease (moderate gingival inflammation and periodontal pocket 4mm or deeper) was of the highest frequency at 13 years old. The proportion of males increased with the advanced state of periodontal disease. 4. A significant correlation was found (X^2-test: α<0.001) between advanced state of periodontal disease and a decrease in tooth brushing time per day. 5. A significant correlation was found between the advance of periodontal disease and gingival bleeding on tooth brushing (X^2-test: α<0.001). Similarly, a correlation was found between the advance of periodontal disease and gingival swelling (X^2-test: α<0.001). 6. A significant correlation was found (X^2-test: α<0.001) between the advance of periodontal disease and aggravation of condition of dental plaque, calculus, dental caries and malalignment.

    DOI: 10.2329/perio.31.1220

    PubMed

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1991208106

  • [A method of protection on out-flow of hydroxyapatite]. Reviewed

    Watanabe Y, Kurihara N, Nakashima K, Onodera O, Ousawa K, Mashima T, Kurihashi Y, Miyata T, Ikeda K

    Nihon Shishubyo Gakkai kaishi   30 ( 4 )   1108 - 1115   1988.12

     More details

    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    Attelocollagen obtained by pepsin treatment from calf skin is very poor antigen. Attelocollagen is the most promising implantable biomaterial because of its lower antigenic propery and excellent tissue compatibility. The puropose of this study is to examine that attelocollagen suppress an out-flow of hydroxyspstite. The subject were 16 patients with moderate to advanced periodontal disease who visited Meika university hospital. The clinical examination were performed immediateiy after the surgery, 1, 2, and 4 weeks after postsurgery. The remains of hydroxyapatite were measured by the rentogenograph and an image analzer system. As a result, The hydroxyapatite in attelocollagen treated group was remained much more than of control group in 4 weeks (p<0.01). In clinical finding, wound healing of attelocollagen treated group was accomplished in 4 weeks and it did not prevent the wound healing of periodontal tissue.

    PubMed

    CiNii Article

    CiNii Books

    researchmap

  • [The study of dentifrice containing Phellodendron amurense extract on periodontal disease (II). The clinical effects of dentifrice containing Phellodendron amurense extract and anti-inflammatory agents]. Reviewed

    Sato I, Watanabe Y, Shimojima T, Onodera O, Ohsawa K, Nakajima K, Kurihashi Y, Mashima T, Kusunoki K, Ikeda K

    Nihon Shishubyo Gakkai kaishi   30 ( 3 )   887 - 900   1988.9

     More details

    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    The purpose of this study was to evaluate the effect of dentifrice containing Phellodendron amurense extract (P.amurense ext.), tranexamic acid, tocopherol acetate and β-glycylrhetinic acid (K dentifrice) on the improvement of periodontal disease comparing with active placebo (A dentifrice) excepted Phellodendron amurense extract from K dentifrice. The subjects were 151 students of Meikai University, School of dentistry who had no serious oral disease. They were performed tooth-brushing twice a day for four weeks. The PMA index, redness, swelling, bleeding and dental plaque accumulation were examined as indices for clinical evaluation of periodontal disease state. This study was conducted with double blind method. The results obtained were as follows: 1. The number of subjects used for statistical analysis was 151 students (K dentifrice group: 76, A dentifrice group: 75). 2. K dentifrice was significantly superior to A dentifrice on the improvement of PMA index (p<0.05) and redness (p<0.05). On the other hand, there was no significant difference on the improvement of swelling, bleeding and dental plaque accumulation between K dentifrice and A dentifrice. 3. The mean reduction rates of K dentifrice and A dentifrice were 37.1% and 30.4% in PMA index, 39.6% and 28.6% in redness respectively. 4. No particular side effects were observed on this clinical study.

    DOI: 10.2329/perio.30.887

    PubMed

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1990140203

  • [Preventive and epidemic research in periodontal disease. 1. Study of preventive and epidemic research in periodontal disease in psychopathic patients]. Reviewed

    Ikeda K, Kusunoki K, Osawa K, Kurihashi Y, Onodera O, Kin H, Iwakawa Y, Nishimoto M

    Nihon Shishubyo Gakkai kaishi   28 ( 2 )   654 - 661   1986.6

     More details

    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    The pourpose of this study was to examined the prevalence of periodontal disease and considered a counterplan of prevention to periodontal disease in psychopathic pahents. 219 psychopatic patients (a schizophreniac in 70〜80%) who had been in the hospital at Yamanashi Ryoyojo in Yamanashi prefecture were investigated the rednes and swelling in gingiva. 42 in 219 psychopathic patients who had been selected by a psychiatrist as a qualified patients for the detailed examinations of periodontal disease were investigated about periodontal pocket depth, inflammation of gingiva, adherent materials on teeth and remaining teeth. And we made survey of the consciousness to dental treatment about 23 items on 44 patients in 219 ones.12 in 44 psychopatic patients who had been selected by a psychiatrist were educated the technique of oral hygiene for two years. The results obtained were as follows : 1. In psychopathic patients, the degree of periodontal disease were higher than mentally normal adults. 2. In psychopathic patients, no effect of motivation to plaque control which be same methods to mentally normal adults were observed namely, psychopatic patients did not have to approach from consciously point of motivation but need the approach from aggressive point of motivation. 3 . It suggest that the motivation to plage control will be useful to treatment of psychopathy.

    DOI: 10.2329/perio.28.654

    PubMed

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1987088506

  • [Systemic considerations in the improvement of periodontal disease]. Reviewed

    Kusunoki K, Shimojima T, Onodera O, Ohsawa K, Miyake T

    Josai Shika Daigaku kiyo. The Bulletin of the Josai Dental University   13 ( 3 )   592 - 602   1984

     More details

  • [Study of orthodontic problems in patients with periodontal disease. 2. The malposition of teeth in periodontal disease]. Reviewed

    Kusunoki K, Shimojima T, Onodera O, Yamamoto O, Iwakawa Y, Ikeda K

    Josai Shika Daigaku kiyo. The Bulletin of the Josai Dental University   13 ( 1 )   83 - 92   1984

     More details

  • [Clinical evaluation of regional myocardial blood flow in patients with hypertrophic cardiomyopathy]. Reviewed

    Sekiguchi H, Fukuhara Y, Koh M, Narita H, Yamanaka T, Fujino Y, Mikuniya A, Onodera O

    Journal of cardiography   13 ( 4 )   1059   1983.12

     More details

▶ display all

Books

  • 厚生労働科学研究費補助金難治性疾患克服研究事業遺伝性脳小血管病の病態機序の解明と治療法の開発班研究報告書

    小野寺, 理

    [小野寺理]  2010.3 

     More details

    Total pages:37p   Language:Japanese

    CiNii Books

    researchmap

  • 転写障害に注目した神経変性過程の解明

    小野寺, 理

    [小野寺理]  2005.3 

     More details

    Total pages:112p  

    CiNii Books

    researchmap

  • アプラタキシン欠損症の臨床遺伝学的検討および病態機序の解明

    辻, 省次, 後藤, 順, 小野寺, 理, 小宅, 睦郎

    辻省次  2004.3 

     More details

    Total pages:22p   Language:English

    CiNii Books

    researchmap

MISC

  • TDP-43 differentially propagates to induce degeneration in the motor circuit

    坪口晋太朗, 中村由香, 石原智彦, 加藤泰介, 佐藤時春, 小山哲秀, 森秀樹, 小池佑佳, 小野寺理, 小野寺理, 上野将紀

    Dementia Japan   37 ( 4 )   2023

  • TDP-43変異型により異なる病態進展特性の解析

    森秀樹, 坪口晋太朗, 佐藤時春, 中村由香, 加藤泰介, 須貝章弘, 小野寺理, 上野将紀

    Dementia Japan   37 ( 4 )   2023

  • 血漿ニューロフィラメント軽鎖と脳脊髄液バイオマーカーの臨床的有用性の検討

    春日健作, 月江珠緒, 五十嵐一也, 五十嵐一也, 石黒敬信, 徳武孝允, 小野寺理, 池内健

    日本神経学会学術大会プログラム・抄録集   64th   2023

  • Long insular artery梗塞の臨床的検討と冠状断画像の有用性

    羽入龍太郎, 坪口晋太朗, 二宮格, 石黒敬信, 今野卓哉, 金澤雅人, 小野寺理

    日本神経学会学術大会プログラム・抄録集   64th   2023

  • CSF1R関連白質脳症:部分欠失を含む新規CSF1R変異の同定と臨床・画像的特徴

    石黒敬信, 今野卓哉, 原範和, 朱斌, 岡田聡, 柴田護, 雑賀玲子, 北野貴也, 祢津智久, 浜由香, 川添僚也, 岩田育子, 佐藤恒太, 春日健作, 宮下哲典, 小野寺理, 池内健

    日本神経学会学術大会プログラム・抄録集   64th   2023

  • 初期にCastleman病が疑われ特徴的な神経伝導検査所見を呈した61歳男性例

    畠山祐樹, 坪口晋太朗, 石黒敬信, 佐治越爾, 細島康宏, 片桐隆幸, 金澤雅人, 小野寺理

    臨床神経学(Web)   63 ( 4 )   2023

  • 脳血管造影検査後の発熱・意識障害で診断された神経核内封入体病(NIID)の一例

    小出伸, 坪口晋太朗, 二宮格, 齋藤太希, 石黒敬信, 佐治越爾, 鈴木倫明, 金澤雅人, 小野寺理

    臨床神経学(Web)   63 ( 3 )   2023

  • 脳脊髄液中CEA測定を行った髄膜癌腫症9例の検討

    渡邉緑, 石黒敬信, 庄子聡, 金澤雅人, 小野寺理

    日本神経学会学術大会プログラム・抄録集   64th   2023

  • 脳生検症例における診断と予後についての後方視的検討

    木崎利哉, 石黒敬信, 棗田学, 大石誠, 柿田明美, 藤井幸彦, 小野寺理, 金澤雅人

    日本神経学会学術大会プログラム・抄録集   64th   2023

  • ポリグルタミン病 治療に向けた次の10年に向けて

    小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   16回   62 - 62   2022.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 【神経核内封入体病・白質脳症】HDLS(hereditary diffuse leukoencephalopathy with spheroids)

    今野 卓哉, 池内 健, 小野寺 理

    脳神経内科   97 ( 1 )   101 - 109   2022.7

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【神経核内封入体病・白質脳症】HTRA1遺伝子変異に関連する脳小血管病

    北原 匠, 加藤 泰介, 小野寺 理

    脳神経内科   97 ( 1 )   71 - 73   2022.7

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 細胞内環境に応じて変形しゲノム編集分子を高効率に送達可能な変幻自在ポリマー

    東 大志, 田原春 徹, 木原 拓也, 小野寺 理沙子, 本山 敬一

    日本DDS学会学術集会プログラム予稿集   38回   95 - 95   2022.6

     More details

    Language:Japanese   Publisher:日本DDS学会  

    researchmap

  • 一般消費者を対象としたプエラリア・ミリフィカの消費者向け安全性情報におけるピクトグラム活用の有用性に関するランダム化比較調査

    種村 菜奈枝, 柿崎 真沙子, 小野寺 理恵, 千葉 剛

    日本臨床栄養学会雑誌   43 ( 1 )   20 - 31   2022.6

     More details

    Language:Japanese   Publisher:(一社)日本臨床栄養学会  

    【目的】プエラリア・ミリフィカの消費者向け安全性情報におけるピクトグラム活用の有用性を評価することである。【方法】2020年12月に消費者1200名を対象にA群(ピクトグラムあり)またはB群(ピクトグラムなし)に1:1で無作為割付をしたが、9名を除外した1191名(A群:594名、B群:597名)を計画書遵守集団として解析した。6種の食品の消費者向け安全性情報や予防行動情報を対象者に提示後、ウェブ上で該当箇所をクリック回答させ、アクセス時間平均をt検定、正答とピクトグラム有無との関連をカイ二乗検定で検討した。【結果】対象者背景は2群間に有意差はなかった。安全性情報の"注意対象者"でアクセス時間に有意な差が見られ(A群:22.9秒、B群:27.4秒、P=.002)、アクセス後の正答とピクトグラム有無との有意な関連が見られた(正答者割合A群:58.8%、B群:49.1%、P=.001)。性別と年齢で層別解析したところ、60歳未満の女性で同様の結果であった。【結論】消費者向け安全性情報に対してピクトグラムを活用することで効果的なリスクコミュニケーション推進確保の可能性が示唆された。(著者抄録)

    researchmap

  • 全身性疾患に伴う脊椎病変 頸椎除圧術後の上肢型筋萎縮側索硬化症の臨床経過

    五十嵐 哲也, 渡辺 慶, 大橋 正幸, 川島 寛之, 三瓶 一弘, 五十嵐 修一, 黒羽 泰子, 小池 亮子, 石原 智彦, 大津 裕, 小野寺 理

    東北整形災害外科学会雑誌   65 ( 1 )   167 - 168   2022.6

     More details

    Language:Japanese   Publisher:東北整形災害外科学会  

    researchmap

  • 家族性アルツハイマー病に対するshRNAポリプレックスの多段階治療戦略

    井上 雅理, 城野 博史, 齊藤 貴志, 小野寺 理沙子, 東 大志, 本山 敬一

    日本DDS学会学術集会プログラム予稿集   38回   127 - 127   2022.6

     More details

    Language:Japanese   Publisher:日本DDS学会  

    researchmap

  • 組織選択的環状オリゴ糖のニーマン・ピック病C型に対する脂質蓄積改善効果

    本山 敬一, 西田 拓実, 横山 龍馬, 竹尾 透, 中潟 直己, 石塚 洋一, 近藤 悠希, 入江 徹美, 小野寺 理沙子, 東 大志

    日本DDS学会学術集会プログラム予稿集   38回   98 - 98   2022.6

     More details

    Language:Japanese   Publisher:日本DDS学会  

    researchmap

  • 臨床医のための神経病理再入門 CARASIL

    齋藤 理恵, 小野寺 理, 柿田 明美

    Clinical Neuroscience   40 ( 6 )   700 - 702   2022.6

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 海綿静脈洞に炎症が波及したリンパ球性下垂体炎の41歳女性例

    木村 嘉克, 上村 昌寛, 森 秀樹, 今野 卓哉, 金澤 雅人, 小野寺 理, 岡本 浩一郎

    臨床神経学   62 ( 4 )   307 - 307   2022.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 禿頭と腰椎症を呈し、ヘテロ接合性HTRA1変異を伴った脳小血管病の31歳女性例

    安田 真人, 杉山 淳比古, 森 雅裕, 水地 智基, 福武 敏夫, 上村 昌寛, 小野寺 理, 桑原 聡

    臨床神経学   62 ( 4 )   314 - 314   2022.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 膵神経内分泌腫瘍の治療中に多発脳梗塞を生じた41歳男性例

    遠山 玄理, 上村 昌寛, 中村 航世, 寺本 傑, 秋山 夏葵, 今野 卓哉, 金澤 雅人, 小野寺 理

    臨床神経学   62 ( 4 )   319 - 319   2022.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 救急医療現場での緊急輸血における院内配送時間の検討

    上村 正巳, 佐藤 美里, 鈴木 克弥, 松原 千秋, 大木 直江, 川合 綾野, 小野寺 理, 新田 正和, 牛木 隆志

    日本輸血細胞治療学会誌   68 ( 2 )   292 - 292   2022.4

     More details

    Language:Japanese   Publisher:(一社)日本輸血・細胞治療学会  

    researchmap

  • 超分子素材を用いたがん選択的ホウ素性中性子捕捉療法薬剤の構築

    伊敷 帆夏, 荒瀬 春輝, 松本 孔貴, 小野寺 理沙子, 本山 敬一, 東 大志

    日本薬学会年会要旨集   142年会   27PO7 - 03   2022.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • シクロデキストリン修飾カチオン性デンドリマー/shRNA複合体を用いた多段階阻害型アルツハイマー病治療薬の開発

    井上 雅理, 城野 博史, 齊藤 貴志, 小野寺 理沙子, 東 大志, 本山 敬一

    日本薬学会年会要旨集   142年会   27H - pm16S   2022.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • タンパク質の製剤特性改善を企図した混合型超分子PEG化剤の構築

    歌津 康生, 古後 徹也, 田原春 徹, 小野寺 理沙子, 本山 敬一, 東 大志

    日本薬学会年会要旨集   142年会   27C - pm07S   2022.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • 新規生体素材の開発を企図した水溶性シクロデキストリンポリカテナン誘導体の調製

    東 大志, 森田 健太郎, 小野寺 理沙子, 本山 敬一

    生体医歯工学共同研究拠点成果報告書   令和3年度   56 - 56   2022.3

     More details

    Language:Japanese   Publisher:東京医科歯科大学生体材料工学研究所  

    researchmap

  • 大腸がん細胞選択的デリバリーを企図した新規抗がん剤としてのマンノース修飾-β-メチルシクロデキストリンの構築

    大野 孝高, 歳納 舞子, 小野寺 理沙子, 東 大志, 本山 敬一

    日本薬学会年会要旨集   142年会   27J - am10S   2022.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • 多発性硬化症と誤診されたヘテロ接合性HTRA-1関連脳小血管病の1例

    北原匠, 坪口晋太朗, 上村昌寛, 野崎洋明, 今野卓哉, 金澤雅人, 小野寺理

    臨床神経学(Web)   62 ( 8 )   2022

  • 進行性の認知機能低下を認めたヘテロ接合性HTRA1関連脳小血管病の2症例

    北原匠, 上村昌寛, 坪口晋太朗, 野崎洋明, 金澤雅人, 小野寺理

    Dementia Japan   36 ( 4 )   2022

  • プリオン病及び遅発性ウイルス感染症に関する調査研究班 プリオン病のサーベイランス・感染予防に関する調査・研究の報告,JACOPの推進

    水澤英洋, 塚本忠, 三條伸夫, 矢部一郎, 青木正志, 小野寺理, 田中章景, 道勇学, 浜口毅, 望月秀樹, 山下徹, 村井弘之, 松下拓也, 佐藤克也, 北本哲之, 阿江竜介, 村山繁雄, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 黒岩義之, 高橋良輔, 田村智英子, 山田正仁, 高尾昌樹

    プリオン病及び遅発性ウイルス感染症に関する調査研究班 令和3年度 総括・分担研究報告書(Web)   2022

  • 神経核内封入体病(NIID)におけるNOTCH2NLC GGCリピート数と臨床所見,画像所見の比較

    樋口陽, 樋口陽, YUSRAN Ady Fitrah, 原範和, 種田朝音, 徳武孝允, 三浦健, 岩淵洋平, 五十嵐修一, 林秀樹, 石黒敬信, 三瓶一弘, 武田勇人, 高橋俊昭, 福原信義, 金澤雅人, 宮下哲典, 小野寺理, 池内健

    Dementia Japan   36 ( 4 )   2022

  • 脳脊髄液バイオマーカーがアルツハイマー病型を呈した大脳皮質基底核症候群の特徴

    石黒敬信, 春日健作, 徳武孝允, 五十嵐一也, 月江珠緒, 今野卓哉, 小野寺理, 池内健

    Dementia Japan   36 ( 4 )   2022

  • 多系統萎縮症における脳脊髄液神経変性マーカーと認知機能の検討

    徳武孝允, 春日健作, 月江珠緒, 石黒敬信, 下畑享良, 小野寺理, 池内健

    Dementia Japan   36 ( 4 )   2022

  • 多系統萎縮症での脳脊髄液バイオマーカーと臨床症状との関連

    徳武孝允, 春日健作, 月江珠緒, 石黒敬信, 下畑享良, 小野寺理, 池内健

    日本神経学会学術大会プログラム・抄録集   63rd   2022

  • 遺伝性脳小血管病モデルから見えてきたmatrisomeの破綻と治療法の展望

    加藤泰介, 眞鍋理一郎, 五十嵐博中, 亀谷富由樹, 齊藤聡, 畠野雄也, 安藤昭一朗, 福永雅喜, 佐藤俊哉, 齋藤理恵, 豊島靖子, 河田浩敏, 村山繁雄, 柿田明美, 長谷川成人, 猪原匡史, 西澤正豊, 辻省次, 小野寺理

    Dementia Japan   36 ( 4 )   2022

  • Matrisomeの擾乱から見た脳小血管病の分子病態と治療法への展望

    加藤泰介, 眞鍋理一郎, 五十嵐博中, 亀谷富由樹, 齊藤聡, 畠野雄也, 安藤昭一朗, 福永雅喜, 佐藤俊哉, 齋藤理恵, 豊島靖子, 河田浩敏, 村山繁雄, 柿田明美, 長谷川成人, 猪原匡史, 西澤正豊, 辻省次, 小野寺理

    Dementia Japan   36 ( 4 )   2022

  • 新規遺伝子多型病原性予測法MOVAのEOAD原因遺伝子への適応

    畠野雄也, 小野寺理, 石原智彦

    Dementia Japan   36 ( 4 )   2022

  • 医師主導治験:ポリグルタミン病に対する蛋白質凝集阻害薬の第II相試験

    石原智彦, 金光祥臣, 他田正義, 他田正義, 池中健介, 高橋祐二, 横田隆徳, 石川欽也, 平野牧人, 永井義隆, 小野寺理

    日本神経学会学術大会プログラム・抄録集   63rd   2022

  • 脳神経疾患克服に向けた研究推進の提言2020、総論

    望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 高橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 青木 吉嗣, 石浦 浩之, 和泉 唯信, 小池 春樹, 島田 斉, 高橋 祐二, 徳田 隆彦, 中嶋 秀人, 波田野 琢, 三澤 園子, 渡辺 宏久, 水澤 英洋, 阿部 康二, 宇川 義一, 梶 龍兒, 亀井 聡, 神田 隆, 吉良 潤一, 楠 進, 鈴木 則宏, 祖父江 元, 高橋 良輔, 辻 省次, 中島 健二, 西澤 正豊, 服部 信孝, 福山 秀直, 峰松 一夫, 村山 繁雄, 望月 秀樹, 山田 正仁, 日本神経学会将来構想委員会

    臨床神経学   61 ( 11 )   709 - 721   2021.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    日本神経学会では,脳神経内科領域の研究・教育・診療,特に研究の方向性や学会としてのあるべき姿について審議し,水澤代表理事が中心となり国などに対して提言を行うために作成委員*が選ばれ,2013年に「脳神経疾患克服に向けた研究推進の提言」が作成された.2014年に将来構想委員会が設立され,これらの事業が継続.今回将来構想委員会で,2020年から2021年の最新の提言が作成された.本稿で,総論部分1)脳神経疾患とは,2)脳神経疾患克服研究の現状,3)脳神経疾患克服研究の意義・必要性,4)神経疾患克服に向けた研究推進体制,5)脳・神経・筋疾患克服へのロードマップ,6)提言の要約版を報告する.(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01550&link_issn=&doc_id=20211116440001&doc_link_id=10.5692%2Fclinicalneurol.cn-001639&url=https%3A%2F%2Fdoi.org%2F10.5692%2Fclinicalneurol.cn-001639&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 多系統萎縮症における脳脊髄液中NG2と臨床症状の検討

    徳武 孝允, 春日 健作, 月江 珠緒, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    臨床神経学   61 ( Suppl. )   S304 - S304   2021.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 当科での成人脊髄性筋萎縮症の診断・治療例

    石原 智彦, 今野 卓哉, 徳武 孝允, 井上 佳奈, 原 賢寿, 小野寺 理

    臨床神経学   61 ( Suppl. )   S322 - S322   2021.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 軟口蓋ミオクローヌスに対する下顎アプローチによる超音波検査

    小出 眞悟, 今野 卓哉, 柏木 健太, 柴田 健太郎, 柳村 文寛, 徳武 孝允, 堅田 慎一, 小野寺 理

    臨床神経学   61 ( Suppl. )   S341 - S341   2021.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 小字症を呈した自己免疫性脳幹脳炎の臨床的特徴

    助川 真響, 畠山 公大, 羽入 龍太郎, 滑川 将気, 大津 裕, 橋田 裕美, 金澤 雅人, 小野寺 理

    臨床神経学   61 ( Suppl. )   S431 - S431   2021.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 犬、猫および豚における血清中の非特異的エステラーゼ活性の比較

    笠井 颯平, 小林 寛, 渕上 仁美, 小野寺 理沙子, O'Brien 悠木子, 高島 諭, 西飯 直仁, 柴田 早苗

    日本獣医学会学術集会講演要旨集   164回   [HSO - 71]   2021.9

     More details

    Language:Japanese   Publisher:(公社)日本獣医学会  

    researchmap

  • 向精神薬の整理により行動・心理症状と運動症状が改善したハンチントン病による認知症の1例

    宮下 真子, 渡部 雄一郎, 本郷 祥子, 小池 直人, 佐治 越爾, 深石 翔, 三上 剛明, 小野寺 理, 染矢 俊幸

    新潟医学会雑誌   135 ( 9 )   209 - 209   2021.9

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 向精神薬の整理により行動・心理症状と運動症状が改善したハンチントン病による認知症の1例

    宮下 真子, 渡部 雄一郎, 本郷 祥子, 小池 直人, 佐治 越爾, 深石 翔, 三上 剛明, 小野寺 理, 染矢 俊幸

    新潟医学会雑誌   135 ( 9 )   209 - 209   2021.9

  • 発熱と白血球増多を伴わず、脳出血で発症したStaphylococcus warneriによる感染性心内膜炎の1例

    種田 朝音, 今野 卓哉, 小野 純花, 徳武 孝允, 小野寺 理

    臨床神経学   61 ( 8 )   563 - 566   2021.8

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • レム睡眠行動障害とてんかんの鑑別を要した1例

    森川 亮, 大竹 将貴, 三上 剛明, 須貝 拓朗, 小出 眞悟, 上村 昌寛, 小野寺 理, 染矢 俊幸

    新潟医学会雑誌   135 ( 8 )   178 - 179   2021.8

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • レム睡眠行動障害とてんかんの鑑別を要した1例

    森川 亮, 大竹 将貴, 三上 剛明, 須貝 拓朗, 小出 眞悟, 上村 昌寛, 小野寺 理, 染矢 俊幸

    新潟医学会雑誌   135 ( 8 )   178 - 179   2021.8

  • 頸椎除圧術後の上肢型筋萎縮索硬化症の臨床経過

    五十嵐 哲也, 渡辺 慶, 大橋 正幸, 川島 寛之, 三瓶 一弘, 五十嵐 修一, 黒羽 泰子, 小池 亮子, 石原 智彦, 大津 裕, 小野寺 理

    日本整形外科学会雑誌   95 ( 2 )   S112 - S112   2021.3

     More details

    Language:Japanese   Publisher:(公社)日本整形外科学会  

    researchmap

  • 高齢発症多系統萎縮症の臨床病理学的検討

    荻根沢 真也, 今野 卓哉, 清水 宏, 他田 真理, 柿田 明美, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   14回   112 - 112   2021.2

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 基底核を主体とするメトロニダゾール脳症を呈した36歳女性例

    岩渕 洋平, 石原 智彦, 今野 卓哉, 徳武 孝允, 小野寺 理

    臨床神経学   61 ( 1 )   62 - 62   2021.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 医学と医療の最前線 脳梗塞に対する細胞療法の最前線

    畠山 公大, 二宮 格, 小野寺 理, 下畑 享良, 金澤 雅人

    日本内科学会雑誌   110 ( 1 )   117 - 123   2021.1

     More details

    Language:Japanese   Publisher:(一社)日本内科学会  

    researchmap

  • 加齢と関連したDNA脱メチル化がTDP-43量の自己調節機構を障害する

    小池佑佳, 須貝章弘, 原範和, 伊藤絢子, 横関明男, 石原智彦, 山岸拓磨, 坪口晋太朗, 他田真理, 池内健, 柿田明美, 小野寺理

    Dementia Japan   35 ( 4 )   2021

  • プリオン病及び遅発性ウイルス感染症に関する調査研究班 プリオン病のサーベイランス・感染予防に関する調査・研究の報告,JACOPの推進

    水澤英洋, 塚本忠, 三條伸夫, 矢部一郎, 青木正志, 小野寺理, 田中章景, 道勇学, 望月秀樹, 阿部康二, 村井弘之, 松下拓也, 佐藤克也, 北本哲之, 阿江竜介, 村山繁雄, 黒岩義之, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 田村智英子, 山田正仁, 高尾昌樹

    プリオン病及び遅発性ウイルス感染症に関する調査研究班 令和2年度 総括・分担研究報告書(Web)   2021

  • Clinicopathologic study of two patients with amyotrophic lateral sclerosis harboring TBK1 mutations

    TADA Mari, HATANO Yuya, TAKESHIMA Akari, SAITO Rie, SAJI Etsuji, TOKUTAKE Takayoshi, ISHIHARA Tomohiko, TOYOSHIMA Yasuko, ONODERA Osamu, KAKITA Akiyoshi

    日本神経学会学術大会プログラム・抄録集   62nd   2021

  • The association of early onset severe cerebral small vessel disease and APOE

    HATANO Yuya, ISHIHARA Tomohiko, UEMURA Masahiro, ONODERA Osamu

    日本神経学会学術大会プログラム・抄録集   62nd   2021

  • ヒト剖検脳に対するMAO-B PETプローブ[<sup>18</sup>F]SMBT-1の結合

    原田龍一, 原田龍一, 堵怡青, 横山裕香, 古本祥三, 工藤幸司, 荒井啓行, 畠野雄也, 石原智彦, 小野寺理, 吉田眞理, 北本哲之, 岩崎靖, 谷内一彦, 岡村信行, 岡村信行

    Dementia Japan   35 ( 4 )   2021

  • 神経変性疾患領域の基盤的調査研究 孤発性ALSにおける認知症発症リスクとしてのAPOE2

    小野寺理, 畠野雄也, 石原智彦, 他田真理, 柿田明美

    神経変性疾患領域の基盤的調査研究 令和2年度 総括・分担研究報告書(Web)   2021

  • 運動失調の医療水準,患者QOLの向上に資する研究班 DRPLAとMJD,SCA6の発症年齢とCAGリピート数の分布の比較

    小野寺理, 畠野雄也, 石原智彦, 廣川祥子

    運動失調症の医療水準,患者QOLの向上に資する研究班 令和2年度 総括・分担研究報告書(Web)   2021

  • 運動失調の医療水準,患者QOLの向上に資する研究班 運動失調症患者登録・自然歴調査J-CAT

    高橋祐二, 水澤英洋, 伊達英俊, 佐々木征行, 池田佳生, 石川欽也, 勝野雅央, 桑原聡, 下畑享良, 高嶋博, 瀧山嘉久, 田中章景, 戸田達史, 花島律子, 矢部一郎, 吉田邦広, 小野寺理

    運動失調症の医療水準,患者QOLの向上に資する研究班 令和2年度 総括・分担研究報告書(Web)   2021

  • 筋強直性ジストロフィーに合併する水頭症はシャント術で改善しうる

    本郷 祥子, 今野 卓哉, 徳武 孝允, 小野寺 理

    臨床神経学   60 ( Suppl. )   S454 - S454   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性

    金澤 雅人, 二宮 格, 上村 昌寛, 下畑 享良, 小野寺 理

    臨床神経学   60 ( Suppl. )   S360 - S360   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経疾患・精神疾患の鑑別における血漿炎症性サイトカインの有用性

    樋口 陽, 春日 健作, 徳武 孝允, 宮下 哲典, 茂木 崇治, 福井 直樹, 横山 裕一, 染矢 俊幸, 小野寺 理, 池内 健

    臨床神経学   60 ( Suppl. )   S377 - S377   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症の確定診断までの時間に与える、初診科、発症部位の検討

    大津 裕, 小池 佑佳, 石原 智彦, 小野寺 理

    臨床神経学   60 ( Suppl. )   S380 - S380   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CARASILの原因遺伝子同定まで 新潟大学脳研究所神経内科第四研究室

    小野寺 理

    BIO Clinica   35 ( 12 )   1124 - 1127   2020.11

     More details

    Language:Japanese   Publisher:(株)北隆館  

    幸運は十分な準備をしていないところでは、つかむことが出来ません。新潟大学脳研究所脳神経内科で、この"禿頭と変形性脊椎症を伴う常染色体劣性白質脳症"の遺伝子を、単離し2009年にNEJMに発表できたのは、まさに、十分な準備をしていたからです。この準備にはひと、文化を育てると言う意味があります。この準備は遡ること20年前から始まります。今回はこのCARASIL同定に至った頃のことを示します。(著者抄録)

    researchmap

  • 脳梗塞に対する低酸素低糖刺激末梢血単核球を用いた細胞療法

    畠山 公大, 金澤 雅人, 二宮 格, 尾前 薫, 木村 泰子, 高橋 哲哉, 小野寺 理, 福島 雅典, 下畑 享良

    脳循環代謝   32 ( 1 )   81 - 81   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本脳循環代謝学会  

    researchmap

  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性の検討

    二宮 格, 金澤 雅人, 上村 昌寛, 小野寺 理

    脳循環代謝   32 ( 1 )   113 - 113   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本脳循環代謝学会  

    researchmap

  • 【脊髄小脳変性症・多系統萎縮症について】[第2部]脊髄小脳変性症の治療の現状と展望

    大津 裕, 今野 卓哉, 石原 智彦, 小野寺 理

    難病と在宅ケア   26 ( 8 )   9 - 12   2020.11

  • 多系統萎縮症における脳脊髄液中NG2とα-シヌクレインの検討

    徳武 孝允, 春日 健作, 月江 珠緒, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    臨床神経学   60 ( Suppl. )   S433 - S433   2020.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ANCA関連脊髄肥厚性硬膜炎の臨床免疫病理学的検討

    中島 章博, 佐治 越爾, 清水 宏, 豊島 靖子, 岡本 浩一郎, 若杉 尚宏, 柳村 文寛, 柳川 香織, 柿田 明美, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   134 - 134   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 認知症と精神疾患の鑑別における血液バイオマーカーの有用性の検討

    樋口 陽, 春日 健作, 徳武 孝允, 宮下 哲典, 茂木 崇治, 横山 裕一, 福井 直樹, 染矢 俊幸, 小野寺 理, 池内 健

    Dementia Japan   34 ( 4 )   527 - 527   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Intracortical and corticospinal spreading of TDP-43 in mouse FTLD/ALS models(和訳中)

    坪口 晋太朗, 中村 由香, 石原 智彦, 加藤 泰介, 小山 哲秀, 佐藤 時春, 吉田 富, 上野 将紀, 小野寺 理

    Dementia Japan   34 ( 4 )   524 - 524   2020.10

     More details

    Language:English   Publisher:(一社)日本認知症学会  

    researchmap

  • 多発性硬化症における大脳萎縮の解析

    若杉 尚宏, 佐治 越爾, 中島 章博, 柳村 文寛, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   106 - 106   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 進行性腎細胞癌へのニボルマブ・イピリムマブ併用療法後に生じた自己免疫性脳炎の1例

    小林 彩夏, 小出 眞悟, 佐治 越爾, 山名 一寿, 河内 泉, 富田 善彦, 小野寺 理

    神経免疫学   25 ( 1 )   131 - 131   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 重症筋無力症合併視神経脊髄炎関連疾患の解析

    佐治 越爾, 中島 章博, 若杉 尚宏, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   115 - 115   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 著明な疼痛と異常感覚で発症した筋萎縮性側索硬化症の1例

    池上 いちこ, 畠山 公大, 羽入 龍太郎, 滑川 将気, 大津 裕, 金澤 雅人, 小野寺 理

    臨床神経生理学   48 ( 5 )   587 - 587   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本臨床神経生理学会  

    researchmap

  • ゲノム編集による遺伝子サイレンシングを用いたDRPLA治療戦略

    安藤 昭一朗, 加藤 泰介, 小池 佑佳, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    Dementia Japan   34 ( 4 )   531 - 531   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 遺伝性脳小血管病の鑑別診断と分子病態

    小野寺 理

    Dementia Japan   34 ( 4 )   424 - 424   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 残存する認知機能を活用し就労継続に効果が得られた意味性認知症の1例

    荒木 亜希, 春日 健作, 樋口 陽, 徳武 孝允, 小野寺 理, 池内 健

    Dementia Japan   34 ( 4 )   489 - 489   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多系統萎縮症における脳脊髄液中NG2と認知機能の検討

    徳武 孝允, 春日 健作, 月江 珠緒, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    Dementia Japan   34 ( 4 )   490 - 490   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 本邦の孤発性ALSにおけるAPOE2の認知症への影響の検討

    畠野 雄也, 石原 智彦, 他田 真理, 柿田 明美, 小野寺 理

    Dementia Japan   34 ( 4 )   521 - 521   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • FTLD/ALSモデルマウスにおけるTDP-43の皮質内と皮質脊髄内での増殖(Intracortical and corticospinal spreading of TDP-43 in mouse FTLD/ALS models)

    坪口 晋太朗, 中村 由香, 石原 智彦, 加藤 泰介, 小山 哲秀, 佐藤 時春, 吉田 富, 上野 将紀, 小野寺 理

    Dementia Japan   34 ( 4 )   524 - 524   2020.10

     More details

    Language:English   Publisher:(一社)日本認知症学会  

    researchmap

  • 認知症と精神疾患の鑑別における血液バイオマーカーの有用性の検討

    樋口 陽, 春日 健作, 徳武 孝允, 宮下 哲典, 茂木 崇治, 横山 裕一, 福井 直樹, 染矢 俊幸, 小野寺 理, 池内 健

    Dementia Japan   34 ( 4 )   527 - 527   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • ゲノム編集による遺伝子サイレンシングを用いたDRPLA治療戦略

    安藤 昭一朗, 加藤 泰介, 小池 佑佳, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    Dementia Japan   34 ( 4 )   531 - 531   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【難病研究の進歩】神経・筋 副腎白質ジストロフィー

    小池 佑佳, 小野寺 理

    生体の科学   71 ( 5 )   410 - 411   2020.10

     More details

    Language:Japanese   Publisher:(公財)金原一郎記念医学医療振興財団  

    <文献概要>副腎白質ジストロフィーは,ABCD1遺伝子変異により生じる先天代謝異常症である。生化学的には極長鎖脂肪酸の蓄積を,病理学的には中枢神経系の脱髄を特徴とするが,その疾患メカニズムは完全には解明されておらず,今なお病態研究は進行中である。一方で,治療に関しては,発症早期における造血幹細胞の移植や遺伝子治療の有効性が示されており,今後ますます早期診断,早期介入の必要性が高まることが想定される。

    researchmap

  • 重症筋無力症合併視神経脊髄炎関連疾患の解析

    佐治 越爾, 中島 章博, 若杉 尚宏, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   115 - 115   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 多発性硬化症における大脳萎縮の解析

    若杉 尚宏, 佐治 越爾, 中島 章博, 柳村 文寛, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   106 - 106   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • ANCA関連脊髄肥厚性硬膜炎の臨床免疫病理学的検討

    中島 章博, 佐治 越爾, 清水 宏, 豊島 靖子, 岡本 浩一郎, 若杉 尚宏, 柳村 文寛, 柳川 香織, 柿田 明美, 小野寺 理, 河内 泉

    神経免疫学   25 ( 1 )   134 - 134   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 進行性腎細胞癌へのニボルマブ・イピリムマブ併用療法後に生じた自己免疫性脳炎の1例

    小林 彩夏, 小出 眞悟, 佐治 越爾, 山名 一寿, 河内 泉, 富田 善彦, 小野寺 理

    神経免疫学   25 ( 1 )   131 - 131   2020.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 脳梗塞に対する低酸素低糖刺激末梢血単核球療法

    畠山 公大, 二宮 格, 小野寺 理, 下畑 享良, 金澤 雅人

    BRAIN and NERVE: 神経研究の進歩   72 ( 10 )   1097 - 1103   2020.10

     More details

    Language:Japanese   Publisher:(株)医学書院  

    <文献概要>近年,脳梗塞に対する細胞療法の研究が盛んに行われているが,既存の細胞療法は,投与細胞の採取や調整に複雑な手技を要するため,一般臨床への普及が難しい。われわれは,末梢血単核球に,低酸素低糖刺激という簡便な刺激を加えることにより,脳梗塞に対して治療効果のある細胞を調整できることを証明した。本稿では,われわれの開発した技術と今後の展望について概説する。

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04871&link_issn=&doc_id=20201012210017&doc_link_id=40022380199&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40022380199&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 著明な疼痛と異常感覚で発症した筋萎縮性側索硬化症の1例

    池上 いちこ, 畠山 公大, 羽入 龍太郎, 滑川 将気, 大津 裕, 金澤 雅人, 小野寺 理

    臨床神経生理学   48 ( 5 )   587 - 587   2020.10

     More details

    Language:Japanese   Publisher:(一社)日本臨床神経生理学会  

    researchmap

  • 【良性成人型家族性ミオクローヌスてんかん】良性成人型家族性ミオクローヌスてんかんの神経病理

    齊ノ内 信, Ramil Gabdulkhaev, 小野寺 理, 柿田 明美

    脳神経内科   93 ( 3 )   305 - 309   2020.9

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • クエチアピン単剤化により精神症状と運動症状が改善したハンチントン病による認知症の1例

    宮下 真子, 渡部 雄一郎, 本郷 祥子, 小池 直人, 佐治 越爾, 深石 翔, 三上 剛明, 小野寺 理, 染矢 俊幸

    精神神経学雑誌   ( 2020特別号 )   S313 - S313   2020.9

     More details

    Language:Japanese   Publisher:(公社)日本精神神経学会  

    researchmap

  • 【良性成人型家族性ミオクローヌスてんかん】良性成人型家族性ミオクローヌスてんかんの神経病理

    齊ノ内 信, Ramil Gabdulkhaev, 小野寺 理, 柿田 明美

    脳神経内科   93 ( 3 )   305 - 309   2020.9

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • progressive型の小字症と運動失調を呈した自己免疫性脳幹脳炎の1例

    畠山 公大, 羽入 龍太郎, 滑川 将気, 大津 裕, 橋田 裕美, 金澤 雅人, 小野寺 理

    日本神経心理学会総会プログラム・予稿集   44回   103 - 103   2020.9

     More details

    Language:Japanese   Publisher:日本神経心理学会  

    researchmap

  • 遺伝性脊髄小脳変性症 病態解明から治療に向けて

    小野寺 理

    脳と発達   52 ( Suppl. )   S68 - S68   2020.8

     More details

    Language:Japanese   Publisher:(一社)日本小児神経学会  

    researchmap

  • 【RAN翻訳と相分離で紐解くリピート病 くり返し配列の"長さ"が発症の原因となる謎に挑む】DNA、RNAを標的としたポリグルタミン病の新規治療戦略

    安藤 昭一朗, 加藤 泰介, 小野寺 理

    実験医学   38 ( 13 )   2191 - 2196   2020.8

     More details

    Language:Japanese   Publisher:(株)羊土社  

    ポリグルタミン病(polyQ病)は、原因遺伝子のエキソン内に存在するCAGリピートの異常伸長により、伸長polyQ鎖を含む変異タンパク質が神経細胞内で凝集する疾患群である。これまで、polyQ病への治療は対症療法によるところが大きかった。しかし、近年の精力的な遺伝子治療研究への取り組みにより、polyQ病に対しても、進行抑制や発症予防につながるような治療アプローチが試みられ、すでにヒトでの臨床試験が行われているものもある。ここでは、アンチセンスオリゴヌクレオチドとCRISPR/Cas9システムを中心に、最近のpolyQ病に対する遺伝子治療研究の動向を概説する。(著者抄録)

    researchmap

  • 頸椎除圧術後の筋萎縮側索硬化症の臨床経過

    五十嵐 哲也, 大橋 正幸, 田仕 英希, 渋谷 洋平, 関本 浩之, 石原 智彦, 大津 裕, 小野寺 理, 渡辺 慶

    東日本整形災害外科学会雑誌   32 ( 3 )   344 - 344   2020.8

     More details

    Language:Japanese   Publisher:東日本整形災害外科学会  

    researchmap

  • 一側視野に限局した複雑幻視を呈した硬膜動静脈瘻の1例

    小出 眞悟, 畠山 公大, 上村 昌寛, 菊池 文平, 長谷川 仁, 小野寺 理

    臨床神経学   60 ( 6 )   425 - 428   2020.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    右側視野内に視野欠損を伴わない複雑幻視を呈した76歳の女性。脳波検査ではT5、P3を焦点とする鋭一過性波を認めた。頭部MRIでは左下部側頭葉を中心に左側頭後頭葉白質に信号変化を認めた。脳血管造影法で左後頭動脈から左横静脈洞に血流を認め、硬膜動静脈瘻(dural arteriovenous fistula;DAVF)と診断した。経動脈塞栓術後に複雑幻視は消失した。本症例の幻視はDAVFに伴うてんかん発作や皮質の血流変化による可能性を考えた。一般に複雑幻視は、てんかん性幻視は全視野にわたって出現し、一側性の場合は欠損視野内に出現する盲視野内幻視となる。本例は視野欠損を伴わずに一側性の複雑幻視が生じた点、DAVFが複雑幻視を呈した点で、貴重な症例と考えた。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200615340005&doc_link_id=130007852588&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007852588&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 肺血栓塞栓症を合併し、奇異性塞栓による後脊髄動脈症候群を呈した潰瘍性大腸炎の56歳女性例

    荻根沢 真也, 上村 昌寛, 大津 裕, 徳武 孝允, 金澤 雅人, 小野寺 理

    臨床神経学   60 ( 5 )   367 - 367   2020.5

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 肺血栓塞栓症を合併し、奇異性塞栓による後脊髄動脈症候群を呈した潰瘍性大腸炎の56歳女性例

    荻根沢 真也, 上村 昌寛, 大津 裕, 徳武 孝允, 金澤 雅人, 小野寺 理

    臨床神経学   60 ( 5 )   367 - 367   2020.5

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 凍瘡様皮疹を契機に診断しえたneuropsychiatric systemic lupus erythematosusの1例

    土田 裕子, 新熊 悟, 安齋 理, 出口 登希子, 片桐 隆幸, 浦部 陽香, 畠山 公大, 堅田 慎一, 小野寺 理, 阿部 理一郎

    臨床皮膚科   74 ( 6 )   395 - 400   2020.5

     More details

    Language:Japanese   Publisher:(株)医学書院  

    <文献概要>75歳,女性.当科初診の2ヵ月前から足趾の冷感,暗紫色調の変化を自覚するようになった.皮疹出現の1ヵ月後に意識障害が生じ,当院に緊急入院した.頭部画像検査で異常所見は認めず,意識障害の原因は不明であった.皮疹に関して当科を紹介され受診した.足趾に凍瘡様皮疹,頬部や耳介部に浸潤の触れる角化性紅斑を認めた.左頬部紅斑の病理組織検査で,表皮真皮境界部の液状変性および真皮付属器周囲にリンパ球を主体とした炎症細胞の浸潤を認めた.凍瘡状ループスに加え汎血球減少,低補体血症,抗核抗体陽性がみられたことから,neuropsychiatric systemic lupus erythematosus(NPSLE)を伴った全身性エリテマトーデスと診断した.意識障害はステロイド全身投与により改善した.エリテマトーデスを疑う皮疹をもつ原因不明の意識障害患者を診察した際,NPSLEを鑑別に挙げ全身を診察することが重要である.

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01559&link_issn=&doc_id=20200603050006&doc_link_id=10.11477%2Fmf.1412206068&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412206068&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Elevated serum pentraxin 3 levels might predict the diagnosis of branch atheromatous disease at a very early stage. International journal

    Itaru Ninomiya, Masato Kanazawa, Masahiro Umemura, Osamu Onodera

    European journal of neurology   2020.4

     More details

    Language:English  

    BACKGROUND: Branch atheromatous disease (BAD) is one of the stroke subtypes caused by occlusion at the origin of a deep penetrating artery of the brain and is associated with a microatheroma or a junctional plaque. Patients with BAD often develop progressive worsening of neurologic deficits, although these patients often present minor stroke with clinical characteristics of lacunar syndrome at the onset. Pentraxin 3 (PTX3) is known to be a key molecule involved in the pathogenesis of atherosclerosis. Although a high level of serum PTX3 is observed in patients with acute coronary syndrome, there are no reports on PTX3 levels in patients with BAD. This study aimed to investigate whether serum PTX3 levels can distinguish BAD from other stroke subtypes. METHODS: We investigated 93 patients with ischemic stroke. Serum PTX3 levels on admission were measured using enzyme-linked immunosorbent assay in patients with BAD and those of other stroke subtypes (each n ≥ 20). RESULTS: The median PTX3 levels in patients with BAD (4840 pg/mL) were higher than those with other subtypes of stroke (3397 pg/mL in lacunar stroke, 1298 pg/mL in large artery atherosclerosis, 1470 pg/mL in cardioaortic embolism, and 1006 pg/mL in control) (all p < 0.01). CONCLUSION: Our results suggest that elevated serum pentraxin 3 levels might predict the diagnosis of BAD at a very early stage.

    DOI: 10.1111/ene.14249

    PubMed

    researchmap

  • 【まれな感染症-ウイルス,細菌,寄生虫,輸入感染症-】脳神経領域のまれな感染症 画像診断のポイント

    岡本 浩一郎, 高橋 陽彦, 鈴木 倫明, 小野寺 理, 柿田 明美, 阿部 博史

    臨床放射線   65 ( 4 )   317 - 324   2020.4

     More details

    Language:Japanese   Publisher:金原出版(株)  

    researchmap

  • 【まれな感染症-ウイルス,細菌,寄生虫,輸入感染症-】脳神経領域のまれな感染症 画像診断のポイント

    岡本 浩一郎, 高橋 陽彦, 鈴木 倫明, 小野寺 理, 柿田 明美, 阿部 博史

    臨床放射線   65 ( 4 )   317 - 324   2020.4

  • 新しい専門医制度に関するシンポジウム〜始まって2年、新しい専門医制度を巡る課題〜 専攻医からの提言 専攻医の立場からの新たな内科専門医制度について

    中村 航世, 佐治 越爾, 金澤 雅人, 小野寺 理

    新潟医学会雑誌   134 ( 4 )   124 - 125   2020.4

     More details

    Language:Japanese   Publisher:新潟医学会  

    2018年4月から新たな内科専門医制度が開始となった。修了要件として56疾患以上の領域での160症例以上の症例登録や、29編の病歴要約などが必要である。56疾患以上の領域での症例登録のためには研修医症例をうまく活用することが大切となる。また、症例登録は500字以内の症例の概略と300字以内の自己省察に加え登録項目が複数あり、160症例を登録するには時間がかかる。病歴要約は指導医が承認した症例登録から作成するので、指導医による承認もまた重要である。新制度が開始されてから約1年半が経過した現時点で、専攻医の立場から、どのような点に注意すると円滑に修了要件を満たせるか考察した。(著者抄録)

    researchmap

  • Multiple System Atrophy Patients Might Develop Nocturnal Urinary Concentration Failure Prior to Orthostatic Hypotension Early in the Disease Course

    Yusuke Sakata, Masato Kanazawa, Masahiro Hatakeyama, Takuya Konno, Tetsutaro Ozawa, Osamu Onodera

    NEUROLOGY   94 ( 15 )   2020.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • 出血性病変が検出されずに広範な脳病変に至ったアミロイドβ関連血管炎の1例

    畠野 雄也, 須貝 章弘, 山岸 拓磨, 中島 章博, 柿田 明美, 小野寺 理

    臨床神経学   60 ( 3 )   187 - 192   2020.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    アミロイドβ関連血管炎(amyloid β-related angiitis)では、皮質や皮質下の微小出血や脳表ヘモジデリンの沈着が、脳MRI上の重要な所見である。我々は、治療前にはこれらの所見を呈さなかったアミロイドβ関連血管炎を提示する。症例は75歳女性。右同名半盲と失語で発症し、昏睡に至った。脳MRIでは、びまん性の軟髄膜造影病変と散在性のDWI高信号病変を認めたが、T2*WIでは微小出血は検出されなかった。病理所見からアミロイドβ関連血管炎と診断した。ステロイド治療により画像所見、臨床症状ともに改善した。治療後のsusceptibility-weighted imaging(SWI)では多数の微小出血を認めた。アミロイドβ関連血管炎の非侵襲的診断のために、微小出血以外の画像の特徴を集積すべきである。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200310190003&doc_link_id=130007822832&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007822832&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • サルコペニア・フレイルの視点からの認知症

    小野寺 理

    Therapeutic Research   41 ( 2 )   91 - 94   2020.2

  • サルコペニア・フレイルの視点からの認知症

    小野寺 理

    Therapeutic Research   41 ( 2 )   91 - 94   2020.2

  • 抗GD1aIgM抗体と抗GT1bIgM抗体が陽性で免疫グロブリン療法が奏功した遠位優位型CIDPの76歳男性例

    羽入 龍太郎, 須貝 章弘, 加藤 怜, 秋山 夏葵, 徳武 孝允, 金澤 雅人, 河内 泉, 小野寺 理

    臨床神経学   60 ( 1 )   87 - 87   2020.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Huntington病の診断、治療、療養の手引き

    中島 健二, 祖父江 元, 長谷川 一子, 饗場 郁子, 青木 正志, 阿部 康二, 池内 健, 小野寺 理, 梶 龍兒, 吉良 潤一, 桑原 聡, 小久保 康昌, 斎藤 加代子, 佐々木 秀直, 佐野 輝, 高橋 良輔, 辻 省次, 戸田 達史, 中川 正法, 野元 正弘, 服部 信孝, 村田 美穂, 村山 繁雄, 望月 秀樹, 森田 光哉, 横田 隆徳, 吉田 眞理, 渡辺 保裕, 保住 功, Huntington病の診断、治療、療養の手引きガイドライン作成委員会

    神経治療学   37 ( 1 )   61 - 104   2020.1

  • 抗GD1aIgM抗体と抗GT1bIgM抗体が陽性で免疫グロブリン療法が奏功した遠位優位型CIDPの76歳男性例

    羽入 龍太郎, 須貝 章弘, 加藤 怜, 秋山 夏葵, 徳武 孝允, 金澤 雅人, 河内 泉, 小野寺 理

    臨床神経学   60 ( 1 )   87 - 87   2020.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Spreading of TDP-43 via direct corticospinal connections in mouse models

    TSUBOGUCHI Shintaro, NAKAMURA Yuka, ISHIHARA Tomohiko, KATO Taisuke, KOYAMA Akihide, SATO Tokiharu, YOSHIDA Yutaka, UENO Masaki, ONODERA Osamu

    日本神経学会学術大会プログラム・抄録集   61st   2020

  • 脳梗塞に対する低酸素低糖刺激末梢血単核球を用いた細胞療法

    畠山公大, 金澤雅人, 二宮格, 尾前薫, 木村泰子, 高橋哲哉, 小野寺理, 福島雅典, 下畑享良

    脳循環代謝(Web)   32 ( 1 )   2020

  • A case of neuropsychiatric systemic lupus erythematosus diagnosed by skin eruption of chilblain lupus

    土田裕子, 新熊悟, 安齋理, 出口登希子, 片桐隆幸, 浦部陽香, 畠山公大, 堅田慎一, 小野寺理, 阿部理一郎

    臨床皮膚科   74 ( 6 )   2020

  • 【ジストニア診療のupdate】ジストニア 遺伝子診断からのアプローチ

    加藤 怜, 石原 智彦, 小野寺 理

    脳神経内科   91 ( 6 )   727 - 738   2019.12

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 外科的介入を受けていない症候性もやもや病の1剖検例

    齋藤 祥二, 齋藤 理恵, 中原 亜紗, 長谷川 仁, 田口 貴博, 上村 昌寛, 本多 忠幸, 伊藤 靖, 小野寺 理, 梅津 哉, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌   133 ( 11-12 )   389 - 389   2019.12

  • 外科的介入を受けていない症候性もやもや病の1剖検例

    齋藤 祥二, 齋藤 理恵, 中原 亜紗, 長谷川 仁, 田口 貴博, 上村 昌寛, 本多 忠幸, 伊藤 靖, 小野寺 理, 梅津 哉, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌   133 ( 11-12 )   389 - 389   2019.12

  • Type IV collagen α1の3'UTRの新規変異による脳小血管病

    酒井 直子, 上村 昌寛, 加藤 泰介, 安藤 昭一朗, 野崎 洋明, 亀井 博之, 加藤 元博, 小野寺 理

    臨床神経学   59 ( Suppl. )   S327 - S327   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS患者の生存期間に与える非侵襲的換気補助療法の影響 レジストリを用いた解析

    熱田 直樹, 横井 大知, 平川 晃弘, 林 直毅, 中村 良一, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 狩野 修, 桑原 聡, 青木 正志, 金井 数明, 小野寺 理, 梶 龍兒, 祖父江 元, JaCALS

    臨床神経学   59 ( Suppl. )   S358 - S358   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 家族性アルツハイマー病で同定された新規PSEN1遺伝子変異の病的意義の検討

    三浦 健, 目崎 直実, Zhu Bin, 村上 涼太, Liu Lixin, 樋口 陽, 石黒 敬信, 月江 珠緒, 原 範和, 春日 健作, 宮下 哲典, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S352 - S352   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 集中的な視標追跡課題訓練による小脳型多系統萎縮症患者の上肢協調性の変化

    田畑 智, 他田 正義, 永井 貴大, 高野 真優子, 渡邉 貴博, 遠藤 祥子, 五十嵐 文枝, 木村 慎二, 小野寺 理

    臨床神経学   59 ( Suppl. )   S443 - S443   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 子宮腺筋症に伴う高CA125が原因と考えられた再発性脳梗塞に対する子宮摘出術の効果

    滑川 将気, 田中 陽平, 高野 弘基, 鈴木 倫明, 源甲斐 信行, 阿部 博史, 鈴木 美保, 郷戸 千賀子, 佐藤 孝明, 小野寺 理

    臨床神経学   59 ( Suppl. )   S326 - S326   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Branch Atheromatous Diseaseにおける急性期の血清Lox-1値の検討

    二宮 格, 金澤 雅人, 下畑 享良, 小野寺 理

    臨床神経学   59 ( Suppl. )   S323 - S323   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • LMNB1関連常染色体優性遺伝性白質脳症の本邦例と既報例の比較

    目崎 直実, 三浦 健, 野崎 洋明, 今野 卓哉, 春日 健作, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S327 - S327   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALSの早期診断は可能か

    大津 裕, 小野寺 理

    Pharma Medica   37 ( 11 )   63 - 65   2019.11

     More details

    Language:Japanese   Publisher:(株)メディカルレビュー社  

    筋萎縮性側索硬化症(ALS)は、病態解明が進み、治験薬の開発が進められている。その成功には、早期診断、早期介入が必要である。ALSを早期診断するためには、神経科学の知識と臨床の知識をつなぎ、本症に早く気付く必要がある。本症の筋力低下の分布には特徴があり、上腕が比較的スペアされ、split handがあれば強く疑う。電気生理学的には、経頭蓋磁気刺激法が上位運動ニューロン障害を捉える点で、神経反復刺激試験での僧帽筋の漸減現象は早期の運動神経障害を検出する点で期待される。血清、髄液中のリン酸化したニューロフィラメントは神経障害のマーカーとなる可能性がある。これらによる早期診断手法の開発が望まれる。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01750&link_issn=&doc_id=20191114250013&doc_link_id=issn%3D0289-5803%26volume%3D37%26issue%3D11%26spage%3D63&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-5803%26volume%3D37%26issue%3D11%26spage%3D63&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • 多系統萎縮症における脳脊髄液バイオマーカーの検討

    徳武 孝允, 春日 健作, 月江 珠緒, 石黒 敬信, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S276 - S276   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脳脊髄液バイオマーカーによるAlzheimer's clinical syndromeの検討

    春日 健作, 月江 珠緒, 原 範和, 樋口 陽, 石黒 敬信, 徳武 孝允, 宮下 哲典, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S217 - S217   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症の自律神経障害評価における二分画蓄尿検査の有用性

    坂田 佑輔, 金澤 雅人, 畠山 公大, 今野 卓哉, 小澤 鉄太郎, 小野寺 理

    臨床神経学   59 ( Suppl. )   S306 - S306   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • LMNB1関連常染色体優性遺伝性白質脳症の本邦例と既報例の比較

    目崎 直実, 三浦 健, 野崎 洋明, 今野 卓哉, 春日 健作, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S327 - S327   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脳脊髄液バイオマーカーによるAlzheimer's clinical syndromeの検討

    春日 健作, 月江 珠緒, 原 範和, 樋口 陽, 石黒 敬信, 徳武 孝允, 宮下 哲典, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S217 - S217   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 集中的な視標追跡課題訓練による小脳型多系統萎縮症患者の上肢協調性の変化

    田畑 智, 他田 正義, 永井 貴大, 高野 真優子, 渡邉 貴博, 遠藤 祥子, 五十嵐 文枝, 木村 慎二, 小野寺 理

    臨床神経学   59 ( Suppl. )   S443 - S443   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症の自律神経障害評価における二分画蓄尿検査の有用性

    坂田 佑輔, 金澤 雅人, 畠山 公大, 今野 卓哉, 小澤 鉄太郎, 小野寺 理

    臨床神経学   59 ( Suppl. )   S306 - S306   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症における脳脊髄液バイオマーカーの検討

    徳武 孝允, 春日 健作, 月江 珠緒, 石黒 敬信, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S276 - S276   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Type IV collagen α1の3'UTRの新規変異による脳小血管病

    酒井 直子, 上村 昌寛, 加藤 泰介, 安藤 昭一朗, 野崎 洋明, 亀井 博之, 加藤 元博, 小野寺 理

    臨床神経学   59 ( Suppl. )   S327 - S327   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Branch Atheromatous Diseaseにおける急性期の血清Lox-1値の検討

    二宮 格, 金澤 雅人, 下畑 享良, 小野寺 理

    臨床神経学   59 ( Suppl. )   S323 - S323   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 家族性アルツハイマー病で同定された新規PSEN1遺伝子変異の病的意義の検討

    三浦 健, 目崎 直実, Zhu Bin, 村上 涼太, Liu Lixin, 樋口 陽, 石黒 敬信, 月江 珠緒, 原 範和, 春日 健作, 宮下 哲典, 小野寺 理, 池内 健

    臨床神経学   59 ( Suppl. )   S352 - S352   2019.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 液-液相分離(LLPS)と非膜性オルガネラが関わる神経変性病態 核内非膜性オルガネラと運動神経変性疾患

    小野寺 理

    Dementia Japan   33 ( 4 )   480 - 480   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 全脳室および後頭蓋窩拡大を呈した水頭症に対し第3脳室底開窓術を行った42歳男性例

    勇 亜衣子, 中村 航世, 太田 智慶, 柳村 文寛, 畠山 公大, 佐治 越爾, 佐野 正和, 河内 泉, 岡本 浩一郎, 小野寺 理

    神経治療学   36 ( 6 )   S231 - S231   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 歯状核赤核・淡蒼球ルイ体萎縮症モデルマウスに対するゲノム編集効果

    小池 佑佳, 加藤 泰介, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    神経治療学   36 ( 6 )   S218 - S218   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 認知症を伴う成人白質脳症の診断

    小野寺 理

    Dementia Japan   33 ( 4 )   468 - 468   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【非翻訳領域の繰り返し配列伸長変異による神経疾患の臨床および病態機序】脆弱X症候群および脆弱X関連振戦/運動失調症候群の臨床

    畠野 雄也, 石原 智彦, 小野寺 理

    脳神経内科   91 ( 4 )   443 - 450   2019.10

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 大脳容積、大脳白質病変に関与する患者因子、網膜変化の検討

    笠原 壮, 横関 明男, 芳野 高子, 福地 健郎, 小野寺 理

    Dementia Japan   33 ( 4 )   559 - 559   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 培養細胞を用いたAβ過剰産生がタウの細胞外分泌へ及ぼす影響の検討

    石黒 敬信, 春日 健作, 樋口 陽, 目崎 直実, 三浦 健, 徳武 孝允, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   545 - 545   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多系統萎縮症における脳脊髄液バイオマーカーと認知機能の検討

    徳武 孝允, 春日 健作, 月江 珠緒, 石黒 敬信, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   531 - 531   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • C9-ALS/FTDモデルショウジョウバエにおけるリピート関連非ATG翻訳の制御

    上山 盛夫, 石黒 太郎, Gendron Tania F, 今野 卓哉, 小山 哲秀, 和田 圭司, 石川 欣也, 小野寺 理, Petrucelli Leonard, 永井 義隆

    Dementia Japan   33 ( 4 )   551 - 551   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 血漿炎症系サイトカインと脳脊髄液バイオマーカーとの関連

    樋口 陽, 春日 健作, Bin Zhu, Lixin Liu, 石黒 敬信, 徳武 孝允, 宮下 哲典, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   548 - 548   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 認知症を伴う成人白質脳症の診断

    小野寺 理

    Dementia Japan   33 ( 4 )   468 - 468   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多系統萎縮症における脳脊髄液バイオマーカーと認知機能の検討

    徳武 孝允, 春日 健作, 月江 珠緒, 石黒 敬信, 樋口 陽, 下畑 享良, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   531 - 531   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 液-液相分離(LLPS)と非膜性オルガネラが関わる神経変性病態 核内非膜性オルガネラと運動神経変性疾患

    小野寺 理

    Dementia Japan   33 ( 4 )   480 - 480   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 血漿炎症系サイトカインと脳脊髄液バイオマーカーとの関連

    樋口 陽, 春日 健作, Bin Zhu, Lixin Liu, 石黒 敬信, 徳武 孝允, 宮下 哲典, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   548 - 548   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 培養細胞を用いたAβ過剰産生がタウの細胞外分泌へ及ぼす影響の検討

    石黒 敬信, 春日 健作, 樋口 陽, 目崎 直実, 三浦 健, 徳武 孝允, 小野寺 理, 池内 健

    Dementia Japan   33 ( 4 )   545 - 545   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 大脳容積、大脳白質病変に関与する患者因子、網膜変化の検討

    笠原 壮, 横関 明男, 芳野 高子, 福地 健郎, 小野寺 理

    Dementia Japan   33 ( 4 )   559 - 559   2019.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多発性硬化症および視神経脊髄炎患者の臨床的特徴 過去28年間における変遷

    佐治 越爾, 中島 章博, 若杉 尚宏, 柳村 文寛, 柳川 香織, 穂苅 万李子, 小野寺 理, 河内 泉

    神経免疫学   24 ( 1 )   144 - 144   2019.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 手内筋にまで炎症が波及し免疫グロブリン大量静注療法が奏功した難治性筋炎の51歳女性例

    中村 航世, 須貝 章弘, 春日 健作, 徳武 孝允, 小野寺 理

    臨床神経学   59 ( 9 )   615 - 615   2019.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • MS/NMO1 多発性硬化症における認知機能障害と頭部MRIを用いたVBM解析

    若杉 尚宏, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   24 ( 1 )   106 - 106   2019.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 急性脳炎・脳炎 抗GABAB受容体抗体脳炎の臨床的・免疫学的解析

    勇 亜衣子, 坂田 佑輔, 柳村 文寛, 今野 卓哉, 佐治 越爾, 小野寺 理, 河内 泉

    神経免疫学   24 ( 1 )   110 - 110   2019.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 本邦における高齢発症視神経脊髄炎の臨床免疫学的特徴 連続73症例の解析から

    中島 章博, 佐治 越爾, 若杉 尚宏, 柳村 文寛, 柳川 香織, 穂苅 万李子, 小野寺 理, 河内 泉

    神経免疫学   24 ( 1 )   144 - 144   2019.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 視神経脊髄炎の病変局所における炎症極性の解析

    柳村 文寛, 佐治 越爾, 若杉 尚宏, 穂苅 万李子, 柳川 香織, 豊島 靖子, 高橋 均, 柿田 明美, 小野寺 理, 河内 泉

    神経免疫学   24 ( 1 )   131 - 131   2019.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • Therapeutic strategy based on genome editing for dentatorubral-pallidoluysian atrophy(和訳中)

    Koike Yuka, 加藤 泰介, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    てんかん研究   37 ( 2 )   549 - 549   2019.9

     More details

    Language:English   Publisher:(一社)日本てんかん学会  

    researchmap

  • 持続性部分てんかんで発症しfalse lateralizationを認めた抗GAD抗体陽性脳炎成人例

    坂田 佑輔, 佐治 越爾, 永井 貴大, 渡邉 緑, 柴田 健太郎, 他田 正義, 河内 泉, 小野寺 理

    てんかん研究   37 ( 2 )   679 - 679   2019.9

     More details

    Language:Japanese   Publisher:(一社)日本てんかん学会  

    researchmap

  • 持続性部分てんかんで発症しfalse lateralizationを認めた抗GAD抗体陽性脳炎成人例

    坂田 佑輔, 佐治 越爾, 永井 貴大, 渡邉 緑, 柴田 健太郎, 他田 正義, 河内 泉, 小野寺 理

    てんかん研究   37 ( 2 )   679 - 679   2019.9

     More details

    Language:Japanese   Publisher:(一社)日本てんかん学会  

    researchmap

  • 【多系統萎縮症-新たな展開】オリーブ橋小脳萎縮症

    中村 航世, 金澤 雅人, 小野寺 理

    Clinical Neuroscience   37 ( 9 )   1057 - 1058   2019.9

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • ATR-X症候群の男児における口腔管理の1例

    中村 由紀, 野上 有紀子, 森岡 沙耶香, 小野寺 早紀, 中島 努, 黒澤 美絵, 岩瀬 陽子, 大島 邦子, 齊藤 一誠, 早崎 治明

    障害者歯科   40 ( 3 )   303 - 303   2019.9

     More details

    Language:Japanese   Publisher:(一社)日本障害者歯科学会  

    researchmap

  • 【Glymphatic system】脳の排泄系と、その関連疾患

    山岸 拓磨, 小野寺 理

    医学のあゆみ   270 ( 13 )   1183 - 1187   2019.9

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    近年、脳実質からの脳脊髄液を介した老廃物排泄に関与する経路が複数提唱された。これまで、中枢神経系においてはリンパ管が存在しないとされ、脳実質からの老廃物のクリアランスは脳室内で産生された脳脊髄液が脳室や脳槽を通過することで生じるsink効果によると考えられてきた。しかし近年、この排泄系で新しい発見が相次いでいる。Alzheimer病をはじめとする蛋白蓄積性の神経変性疾患では、脳内での蛋白の産生とクリアランスの不均衡が異常蛋白蓄積の要因とされ、これまでクリアランス系では分解機構に主眼が置かれていたが、近年、その排泄系に注目が集まっている。それらはglymphatic system、intramural peri-arterial drainage pathway(IPAD)、髄膜リンパ管(meningeal lymphatic vessel)である。これらの発見は、蛋白蓄積性の神経変性疾患の排泄系を介した病態理解や、新たな治療ターゲットとして期待されている。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00060&link_issn=&doc_id=20190927030001&doc_link_id=%2Faa7ayuma%2F2019%2F027013%2F002%2F1183-1187%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2019%2F027013%2F002%2F1183-1187%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • ゲノム編集による歯状核赤核淡蒼球ルイ体萎縮症の治療戦略(Therapeutic strategy based on genome editing for dentatorubral-pallidoluysian atrophy)

    Koike Yuka, 加藤 泰介, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    てんかん研究   37 ( 2 )   549 - 549   2019.9

     More details

    Language:English   Publisher:(一社)日本てんかん学会  

    researchmap

  • 【脳の自浄システムとしてのアストロサイトとglymphaticシステム】神経脳小血管単位による排泄機構と疾病との関係

    安藤 昭一朗, 上村 昌寛, 小野寺 理

    Dementia Japan   33 ( 3 )   257 - 262   2019.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【小脳学習説Marr-Albus-Ito理論の50年】機能障害と治療 一本鎖DNA損傷と小脳変性症

    横関 明男, 他田 正義, 小野寺 理

    Clinical Neuroscience   37 ( 8 )   989 - 992   2019.8

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 視野欠損を伴わず右視野に限局する複雑幻視を呈した硬膜動静脈瘻の1例

    畠山公大, 小出眞悟, 上村昌寛, 菊池文平, 長谷川仁, 藤井幸彦, 小野寺理

    日本神経心理学会総会プログラム・予稿集   43回   86 - 86   2019.7

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 多系統萎縮症の自律神経障害評価における二分画蓄尿検査の有用性

    坂田 佑輔, 金澤 雅人, 畠山 公大, 今野 卓哉, 小澤 鉄太郎, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   126 - 126   2019.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 環軸椎後方固定術11年後に脳梗塞を繰り返した46歳男性例

    柴田 健太郎, 坂田 佑輔, 佐治 越爾, 石原 智彦, 小野寺 理, 平野 徹

    臨床神経学   59 ( 7 )   465 - 465   2019.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 幻覚と衝動制御障害からオセロ症候群へ発展した進行期パーキンソン病の2例

    秋山 夏葵, 今野 卓哉, 畠山 公大, 徳武 孝允, 春日 健作, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   117 - 117   2019.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 個別の指定難病 A)神経・筋系

    波多野琢, 服部信孝, 水澤英洋, 吉川弘明, 新野正明, 寳金清博, 伊東雅基, 佐々木秀直, 工藤興亮, 渡辺保裕, 中島健二, 古和久典, 小池春樹, 祖父江元, 下畑享良, 松村剛, 松村剛, 橋詰淳, 大原寛明, 高橋良輔, 齋藤加代子, 山野嘉久, 和田健二, 浜口毅, 山田正仁, 中川正法, 岡明, 鈴木直輝, 青木正志, 高橋俊明, 小牧宏文, 桑原聡, 青天目信, 森田光哉, 細矢光亮, 菅野秀宣, 伊藤進, 保住功, 錦織千佳子, 渡邊修, 楠進, 長谷川一子, 水口雅, 上村昌寛, 小野寺理, 三牧正和, 川合謙介, 藤井敬之, 吉良潤一, 臼井直敬, 中村雅之, 佐野輝, 久保田智哉, 高橋正紀, 今野卓哉, 小野寺理, 三浦義治, 野中雄一郎, 加藤光広, 加藤光広, 今井克美, 大橋博文, 阿部裕一, 久保田雅也, 小坂仁, 吉田誠克, 高橋幸利, 福岡正隆, 武内俊樹, 高橋孝雄, 小崎健次郎, 小笠原真志, 西野一三, 池田浩子, 杉江和馬, 齋藤貴志, 池田仁, 小林勝弘, 大野欽司, 林由起子, 浜野晋一郎, 日暮憲道, 廣瀬伸一, 平澤恵理, 坪井義夫, 伊藤雅之, 高田真利子, 戸田達史, 池田昭夫, 山本俊至, 村上良子

    日本医師会雑誌   148 ( 特別1 )   S115 - S116   2019.6

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 【指定難病ペディア2019】個別の指定難病 神経・筋系 皮質下梗塞と白質脳症を伴う常染色体優性脳動脈症(CADASIL)[指定難病124]

    上村 昌寛, 小野寺 理

    日本医師会雑誌   148 ( 特別1 )   S111 - S111   2019.6

     More details

    Language:Japanese   Publisher:(公社)日本医師会  

    researchmap

  • 【脳血管と認知症】基礎 ペリサイトによる脳の堅牢性の維持と破綻による疾患との関連

    加藤 泰介, 小野寺 理

    最新医学   74 ( 6 )   739 - 743   2019.6

     More details

    Language:Japanese   Publisher:(株)最新医学社  

    ペリサイトは脳微小血管に存在する壁細胞の一種であり、近年、その多様かつ重要な機能が明らかとされたことにより、多くの研究者が注目することとなった。その機能は脳血管系の形態形成から脳微小循環制御、炎症メディエーターとしての機能など多岐にわたる。また、その障害による疾患への関与からも注目を集めている。本稿では、これまでに明らかとされたペリサイトに関する多様な知見を総論する。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00516&link_issn=&doc_id=20190614050003&doc_link_id=%2Fap7saisa%2F2019%2F007406%2F004%2F0739-0743%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap7saisa%2F2019%2F007406%2F004%2F0739-0743%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 【嚥下障害と誤嚥性肺炎】主な神経疾患の嚥下障害の臨床 多系統萎縮症

    安藤 昭一朗, 金澤 雅人, 小野寺 理

    Clinical Neuroscience   37 ( 5 )   555 - 557   2019.5

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 眼筋症状のみで経過し、発症から8年後に初めて球麻痺症状を呈した抗MuSK抗体陽性重症筋無力症の76歳女性

    北原 匠, 上村 昌寛, 熊谷 航一郎, 柳村 文寛, 中村 航世, 茂木 崇秀, 河内 泉, 小野寺 理

    臨床神経学   59 ( 5 )   305 - 305   2019.5

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 高度の記憶障害と歩行障害を呈し、治療により劇的に改善した抗GABAB受容体抗体脳炎の60歳男性例

    坂田 佑輔, 今野 卓哉, 五十嵐 一也, 浦部 陽香, 徳武 孝允, 野嵜 幸一郎, 河内 泉, 小野寺 理

    臨床神経学   59 ( 4 )   220 - 220   2019.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 整形外科領域に紛れる筋萎縮性側索硬化症を見逃さないために

    小野寺 理

    臨床整形外科   54 ( 4 )   381 - 386   2019.4

     More details

    Language:Japanese   Publisher:(株)医学書院  

    <文献概要>はじめに 筋萎縮性側索硬化症(amyotrophic lateral sclerosis:ALS)は成人発症の致死的な進行性の神経変性疾患である.永年,その解決の糸口が見つからなかった本症であるが,近年,病態解明が進み,数多くの病態修飾薬の開発がなされている.しかし,その効果は乏しい.一般に,進行性の疾病の場合,治療効果を上げるためには,早期介入が必要なことは言うまでもない.ALSでも,その進行メカニズムが判明し,早期介入の必要性を示唆する病態が明らかとなってきている.しかし,本症ではいまだに,診断に直結する生化学的マーカーは得られておらず,それゆえ,診断において理学所見の意義は大きい.ALSは四肢から始まるものと,球麻痺から始まるものとに大別されるが,本症の半数以上は,四肢の筋力低下で気付かれる.よって,最初に整形外科を受診することが多い.日本では,実に四肢発症者の48%,球麻痺型でも13%が整形外科を初診している.結果として34%が整形外科を受診する.本症の予後を考えると,できるだけ早く正しい診断することは重要である.このことから,本症の診断面で整形外科医の果たす役割は大きい.本稿では整形外科診療に紛れる本疾患について最新の知見と,それに基づく診療のヒントについて紹介したい.しかし,後述するように,多くの患者さんでは,髄節レベルと臨床症状の乖離を認める.このような乖離は頸椎症による二次運動神経細胞の圧迫性の病態では認められることが少ない.しかし,近年の一次運動野の知見により,一次運動神経領域からALSの病態が始まると考えれば,この髄節との不一致も説明できる可能性がある.

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01554&link_issn=&doc_id=20190416080011&doc_link_id=10.11477%2Fmf.1408201334&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408201334&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 本年の動向 成人発症遺伝性白質脳症の医療基盤

    今野 卓哉, 野崎 洋明, 池内 健, 小野寺 理

    Annual Review神経   2019   82 - 88   2019.3

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 医学と医療の最前線 Glymphatic systemと脳小血管機能不全

    上村 昌寛, 小野寺 理

    日本内科学会雑誌   108 ( 3 )   582 - 586   2019.3

  • 【脳血管障害の最近の進歩】単一遺伝子異常による脳小血管病

    酒井 直子, 上村 昌寛, 小野寺 理

    Medical Science Digest   45 ( 3 )   165 - 168   2019.3

     More details

    Language:Japanese   Publisher:(株)ニュー・サイエンス社  

    脳小血管病とは穿通枝動脈、毛細血管などの病変により生じる神経疾患の総称である。脳小血管病では神経活動に応じた血流供給に支障をきたし、認知症などの原因となると推定される。脳小血管病の分子病態はまだ不明な点が多い。近年、複数の遺伝性脳小血管病が報告され、これらの疾患の解析を通じて、分子病態が解明され、新たな治療法の開発に繋がることが期待されている。本稿では遺伝性脳小血管病の代表的疾患であるCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephatopathy(CADASIL)とCerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephatopathy(CARASIL)について概説する。(著者抄録)

    researchmap

  • 各種疾患 変性疾患 小脳障害の定量評価法 SCD治療開発を見据えた評価法開発の取組み

    他田 正義, 小野寺 理

    Annual Review神経   2019   216 - 224   2019.3

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • Time- and extent-dependent effect of neuronal activation on APP processing

    ISHIGURO Takanobu, KASUGA Kensaku, SAITO Kento, MEZAKI Naomi, MIURA Takeshi, TOKUTAKE Takayoshi, ONODERA Osamu, IKEUCHI Takeshi

    日本神経学会学術大会プログラム・抄録集   60th   2019

  • 高度の記憶障害と歩行障害を呈し,治療により劇的に改善した抗GABA<sub>B</sub>受容体抗体脳炎の60歳男性例

    坂田佑輔, 今野卓哉, 五十嵐一也, 浦部陽香, 徳武孝允, 野嵜幸一郎, 河内泉, 小野寺理

    臨床神経学(Web)   59 ( 4 )   2019

  • プリオン病及び遅発性ウイルス感染症に関する調査研究 プリオン病のサーベイランス・感染予防に関する調査・研究の報告,JACOPの推進

    水澤英洋, 塚本忠, 三條伸夫, 佐々木秀直, 青木正志, 小野寺理, 田中章景, 道勇学, 望月秀樹, 阿部康二, 村井弘之, 松下拓也, 佐藤克也, 北本哲之, 中村好一, 村山繁雄, 黒岩義之, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 田村智英子, 山田正仁, 桑田一夫

    プリオン病及び遅発性ウイルス感染症に関する調査研究 平成30年度 総括・分担研究報告書(Web)   2019

  • COX10変異とPMP22欠失を伴った白質脳症の一家系 分子遺伝学的解析

    石黒 敬信, 黒羽 泰子, 原 範和, 目崎 直実, 三浦 健, 春日 健作, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 他田 真理, 河内 泉, 柿田 明美, 小野寺 理, 小池 亮子, 池内 健

    臨床神経学   58 ( Suppl. )   S327 - S327   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PSP Rating Scaleによる進行性核上性麻痺の経時的変化に関する検討

    瀧川 洋史, 池内 健, 饗場 郁子, 森田 光哉, 小野寺 理, 下畑 享良, 徳田 隆彦, 村山 繁雄, 長谷川 一子, 古和 久典, 花島 律子, 中島 健二, JALPACコンソーシアム

    臨床神経学   58 ( Suppl. )   S261 - S261   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • COX10変異とPMP22欠失を伴った白質脳症の一家系 臨床病理学的解析

    黒羽 泰子, 石黒 敬信, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 他田 真理, 河内 泉, 柿田 明美, 小野寺 理, 池内 健, 小池 亮子

    臨床神経学   58 ( Suppl. )   S327 - S327   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【研修医が知っておきたい神経疾患の診断と治療】運動失調症の診断と治療

    小野寺 理

    月刊レジデント   11 ( 10 )   74 - 81   2018.12

     More details

    Language:Japanese   Publisher:(株)医学出版  

    <Point1>小脳の解剖と機能を説明できる。<Point2>運動失調症で現れる臨床症状を説明できる。<Point3>運動失調症をきたす疾患を部位、発症形式ごとに挙げられる。<Point4>運動失調症をきたす脳血管障害を見逃さないようにする。(著者抄録)

    researchmap

  • 新ガイドライン 本邦における常染色体劣性遺伝、X染色体連鎖性の失調症

    横関 明男, 他田 正義, 小野寺 理

    臨床神経学   58 ( Suppl. )   S71 - S71   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS診断におけるAwaji基準の有用性に関する、当科剖検例での後方視的検討

    茂木 崇秀, 石原 智彦, 竹島 明, 他田 真理, 他田 正義, 柿田 明美, 小野寺 理

    臨床神経学   58 ( Suppl. )   S265 - S265   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS関連遺伝子からの病態解明について overview

    小野寺 理

    臨床神経学   58 ( Suppl. )   S79 - S79   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脊髄動静脈瘻症例における水頭症と脳脊髄液Froin徴候

    滑川 将気, 中島 章博, 石原 智彦, 中村 公彦, 他田 正義, 小野寺 理

    臨床神経学   58 ( Suppl. )   S338 - S338   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 視標追跡課題を用いた脊髄小脳変性症患者の自然歴評価と治療効果判定

    永井 貴大, 他田 正義, 徳永 純, 西澤 正豊, 小野寺 理

    臨床神経学   58 ( Suppl. )   S350 - S350   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 成人発症脳小血管病を呈する一卵性双生児に認めたCOL4A1スプライスサイト多型の検討

    酒井 直子, 野崎 洋明, 小野寺 理

    臨床神経学   58 ( Suppl. )   S339 - S339   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 常染色体劣性脊髄小脳失調症の家系におけるC12orf4の新規変異と臨床的特徴

    長谷川 有香, 石原 智彦, 笠原 壮, 黒羽 泰子, 高橋 哲哉, 松原 奈絵, 小野寺 理, 小池 亮子

    臨床神経学   58 ( Suppl. )   S265 - S265   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • COX10変異とPMP22欠失を伴った白質脳症の一家系 分子遺伝学的解析

    石黒 敬信, 黒羽 泰子, 原 範和, 目崎 直実, 三浦 健, 春日 健作, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 他田 真理, 河内 泉, 柿田 明美, 小野寺 理, 小池 亮子, 池内 健

    臨床神経学   58 ( Suppl. )   S327 - S327   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • COX10変異とPMP22欠失を伴った白質脳症の一家系 臨床病理学的解析

    黒羽 泰子, 石黒 敬信, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 他田 真理, 河内 泉, 柿田 明美, 小野寺 理, 池内 健, 小池 亮子

    臨床神経学   58 ( Suppl. )   S327 - S327   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • MSA-Pと鑑別を要したPARK8の75歳女性例

    林 秀樹, 石原 智彦, 斎藤 奈つみ, 安藤 昭一朗, 小野寺 理

    臨床神経学   58 ( 12 )   779 - 779   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 進行性核上性麻痺における臨床型別臨床経過の検討 多施設共同前向きコホート研究

    饗場 郁子, 池内 健, 瀧川 洋史, 徳田 隆彦, 下畑 享良, 森田 光哉, 村山 繁雄, 小野寺 理, 長谷川 一子, 古和 久典, 花島 律子, 中島 健二, JALPACコンソーシアム

    臨床神経学   58 ( Suppl. )   S211 - S211   2018.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • アナグレリドの内服中止後、多発する時相の異なる脳梗塞を認めた本態性血小板血症を有する44歳女性例

    浦部 陽香, 畠山 公大, 堅田 慎一, 小野寺 理, 山岸 拓磨, 徳武 孝允

    神経治療学   35 ( 6 )   S237 - S237   2018.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • iPadを用いた小脳性運動失調の定量評価法の開発 脊髄小脳変性症患者の自然歴評価と治療効果判定

    永井 貴大, 他田 正義, 小野寺 理

    神経治療学   35 ( 6 )   S253 - S253   2018.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 集中的な視標追跡課題訓練による小脳性運動失調患者の上肢協調性の変化

    田畑 智, 他田 正義, 能村 友紀, 永井 貴大, 高野 真優子, 遠藤 祥子, 渡邉 貴博, 五十嵐 文枝, 木村 慎二, 小野寺 理

    The Japanese Journal of Rehabilitation Medicine   55 ( 秋季特別号 )   S460 - S460   2018.10

     More details

    Language:Japanese   Publisher:(公社)日本リハビリテーション医学会  

    researchmap

  • 脳脊髄液バイオマーカーAT(N)systemをもちいた認知症関連疾患の再考

    春日健作, 月江珠緒, 石黒敬信, 石黒敬信, 三浦健, 目崎直実, 徳武孝允, 宮下哲典, 小野寺理, 池内健

    Dementia Japan   32 ( 3 )   417 - 417   2018.9

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 佐渡市における和太鼓を用いた認知症予防事業 認知機能トレーニングとの比較

    三浦 健, 目崎 直実, 濱田 香津恵, 森本 芳典, 石黒 敬信, 春日 健作, 小野寺 理, 池内 健

    Dementia Japan   32 ( 3 )   487 - 487   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 神経細胞興奮がβ-amyloid precursor protein(APP)processingへ及ぼす影響

    石黒 敬信, 春日 健作, 斎藤 健智, 目崎 直実, 三浦 健, 小野寺 理, 池内 健

    Dementia Japan   32 ( 3 )   423 - 423   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 成人白質変化と認知症 遺伝性成人白質脳症の知見から

    小野寺 理

    Dementia Japan   32 ( 3 )   346 - 346   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • AARS2変異による成人発症大脳白質脳症の分子臨床遺伝学的解析

    目崎 直実, 原 範和, 月江 珠緒, 馬場 徹, 緒方 利安, 三浦 健, 樋口 陽, 石黒 敬信, 野崎 洋明, 春日 健作, 森 悦朗, 坪井 義夫, 小野寺 理, 池内 健

    Dementia Japan   32 ( 3 )   455 - 455   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 病理学的に同定した進行性の白質病変を認めた脳アミロイドβ関連血管炎の2症例

    北原 匠, 上村 昌博, 柳村 文博, 畠野 雄也, 須貝 章弘, 河内 泉, 柿田 明美, 小野寺 理

    Dementia Japan   32 ( 3 )   482 - 482   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多系統萎縮症における認知症関連・脳脊髄液バイオマーカーの検討

    徳武 孝允, 春日 健作, 月江 珠緒, 石黒 敬信, 三浦 健, 目崎 直実, 下畑 享良, 小野寺 理, 池内 健

    Dementia Japan   32 ( 3 )   465 - 465   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 視神経脊髄炎関連疾患におけるジェンダー効果の解析

    佐治 越爾, 中島 章博, 若杉 尚宏, 柳村 文寛, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   23 ( 1 )   129 - 129   2018.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 急性脳炎・脳症 Cortical midline structuresを主病変とする抗GAD抗体関連自己免疫性脳炎の1例

    坂田 佑輔, 佐治 越爾, 永井 貴大, 渡邉 緑, 柴田 健太郎, 他田 正義, 河内 泉, 小野寺 理

    神経免疫学   23 ( 1 )   97 - 97   2018.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 多発性硬化症の縦断的認知機能動態とQOLの解析

    若杉 尚宏, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 柳川 香織, 小野寺 理, 河内 泉

    神経免疫学   23 ( 1 )   130 - 130   2018.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 脳の自浄システムとしてのアストロサイトとglymphaticシステム 神経脳小血管単位による排泄機構と疾病との関連

    小野寺 理

    Dementia Japan   32 ( 3 )   364 - 364   2018.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 自己免疫性脳炎 Neuromyelitis opticaにおけるTRPM4分子発現動態の解析

    穂苅 万李子, 佐治 越爾, 柳村 文寛, 若杉 尚宏, 柳川 香織, 豊島 靖子, 柿田 明美, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   23 ( 1 )   87 - 87   2018.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • MS/NMO 視神経脊髄炎におけるmelanoma cell adhesion moleculeの病理学的検討

    柳村 文寛, 佐治 越爾, 若杉 尚宏, 穂苅 万李子, 柳川 香織, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 河内 泉

    神経免疫学   23 ( 1 )   93 - 93   2018.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • T2*強調画像で微小出血を認めず、軟髄膜病変が急速に拡大したアミロイドβ関連血管炎の75歳女性例

    畠野 雄也, 須貝 章弘, 山岸 拓磨, 中島 章博, 他田 正義, 河内 泉, 小野寺 理

    臨床神経学   58 ( 8 )   529 - 529   2018.8

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症における認知機能低下の予測因子の検討

    下畑 享良, 畠山 公大, 佐藤 朋江, 高橋 哲哉, 金澤 雅人, 小野寺 理, 西澤 正豊

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   89 - 89   2018.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 臨床経過および画像所見よりMSA-Pとの鑑別を要したPARK8の一例

    石原 智彦, 林 秀樹, 齋藤 奈つみ, 安藤 昭一朗, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   100 - 100   2018.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 脳小血管病

    小野寺 理

    神経治療学   35 ( 4 )   423 - 426   2018.7

  • 臨床経過および画像所見よりMSA-Pとの鑑別を要したPARK8の一例

    石原 智彦, 林 秀樹, 齋藤 奈つみ, 安藤 昭一朗, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   100 - 100   2018.7

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 意味記憶障害、エピソード記憶障害を呈した皮質基底核症候群の一例

    畠山 公大, 林 秀樹, 徳武 孝允, 小野寺 理

    日本神経心理学会総会プログラム・予稿集   42回   87 - 87   2018.6

     More details

    Language:Japanese   Publisher:日本神経心理学会  

    researchmap

  • 意味記憶障害、エピソード記憶障害を呈した皮質基底核症候群の一例

    畠山 公大, 林 秀樹, 徳武 孝允, 小野寺 理

    日本神経心理学会総会プログラム・予稿集   42回   87 - 87   2018.6

     More details

    Language:Japanese   Publisher:日本神経心理学会  

    researchmap

  • IDH変異型グリオーマの診断と術中治療―コラボレーションを通して実現を目指す―

    棗田学, 阿部英明, 岡田正康, 五十嵐博中, 中田力, 小山哲秀, 小野寺理, 柿田明美, 大石誠, 藤井幸彦

    日本蛋白質科学会年会プログラム・要旨集   18th   25   2018.5

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 【パーキンソン病(第2版)-基礎・臨床研究のアップデート-】 検査・診断 関連疾患 進行性核上性麻痺 臨床病型の多様性およびパーキンソン病との鑑別診断

    金澤 雅人, 小野寺 理, 饗場 郁子

    日本臨床   76 ( 増刊4 パーキンソン病 )   330 - 337   2018.5

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 【脳タンパク質老化と認知症制御】 脳タンパク質とその標的RNAの均衡と破綻

    小池 佑佳, 須貝 章弘, 小野寺 理

    細胞   50 ( 6 )   303 - 306   2018.5

     More details

    Language:Japanese   Publisher:(株)ニュー・サイエンス社  

    神経変性疾患を特徴づける脳内に異常に蓄積するタンパク質には、RNA結合タンパク質が多く含まれる。RNA結合タンパク質は、タンパク質をコードするmRNAのみならず、mRNA前駆体のイントロン領域や非翻訳領域、さらにはノンコーディングRNAに対しても結合し、広範な細胞内機能を担っている。特定の脳タンパク質が異常に蓄積する神経変性疾患の病態を理解し、これを制御するためには、RNA結合タンパク質とこれと関連するRNA代謝の両面からのアプローチが必要となる。近年、RNA結合タンパク質とその標的RNAの量の不均衡が細胞毒性と関連することを示唆する報告が集まりつつある。RNA結合タンパク質と関連するRNAからなるロバストな細胞内制御機構の背後に潜む脆弱因子を特定し、制御することが、これらの脳疾患の克服につながるものと期待したい。(著者抄録)

    researchmap

  • 【パーキンソン病(第2版)-基礎・臨床研究のアップデート-】検査・診断 関連疾患 進行性核上性麻痺 臨床病型の多様性およびパーキンソン病との鑑別診断

    金澤 雅人, 小野寺 理, 饗場 郁子

    日本臨床   76 ( 増刊4 パーキンソン病 )   330 - 337   2018.5

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 【脳タンパク質老化と認知症制御】脳タンパク質とその標的RNAの均衡と破綻

    小池 佑佳, 須貝 章弘, 小野寺 理

    細胞   50 ( 6 )   303 - 306   2018.5

     More details

    Language:Japanese   Publisher:(株)ニュー・サイエンス社  

    神経変性疾患を特徴づける脳内に異常に蓄積するタンパク質には、RNA結合タンパク質が多く含まれる。RNA結合タンパク質は、タンパク質をコードするmRNAのみならず、mRNA前駆体のイントロン領域や非翻訳領域、さらにはノンコーディングRNAに対しても結合し、広範な細胞内機能を担っている。特定の脳タンパク質が異常に蓄積する神経変性疾患の病態を理解し、これを制御するためには、RNA結合タンパク質とこれと関連するRNA代謝の両面からのアプローチが必要となる。近年、RNA結合タンパク質とその標的RNAの量の不均衡が細胞毒性と関連することを示唆する報告が集まりつつある。RNA結合タンパク質と関連するRNAからなるロバストな細胞内制御機構の背後に潜む脆弱因子を特定し、制御することが、これらの脳疾患の克服につながるものと期待したい。(著者抄録)

    researchmap

  • 三叉神経節から脊髄路核までMRIで造影効果を伴う病変を認め、バラシクロビルが奏功した38歳男性例

    加藤 怜, 須貝 章弘, 山岸 拓磨, 他田 正義, 河内 泉, 小野寺 理

    臨床神経学   58 ( 4 )   253 - 253   2018.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 三叉神経節から脊髄路核までMRIで造影効果を伴う病変を認め、バラシクロビルが奏功した38歳男性例

    加藤 怜, 須貝 章弘, 山岸 拓磨, 他田 正義, 河内 泉, 小野寺 理

    臨床神経学   58 ( 4 )   253 - 253   2018.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Identification and Functional Assay of Novel CSF1R Mutations in Patients with Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia

    Takeshi Miura, Naomi Mezaki, Takanobu Ishiguro, Takayoshi Tokutake, Kensaku Kasuga, Takuya Konno, Hiroaki Nozaki, Osamu Onodera, Takeshi Ikeuchi

    NEUROLOGY   90   2018.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • これって神経内科の病気? 整形外科外来に紛れ込む神経疾患の最近の話題

    小野寺 理

    日本整形外科学会雑誌   92 ( 3 )   S619 - S619   2018.3

     More details

    Language:Japanese   Publisher:(公社)日本整形外科学会  

    researchmap

  • 成人発症神経核内封入体病の封入体形成における、TGF-βシグナル関連タンパクの関与の検討

    佐藤 朋江, 小野寺 理

    新潟医学会雑誌   132 ( 3 )   83 - 92   2018.3

     More details

    Language:Japanese   Publisher:新潟医学会  

    神経核内封入体病(Neuronal intranuclear inclusion disease;NIID)はエオジン好性、かつ、p62陽性の核内封入体(Nuclear inclusion;NI)が、中枢神経系の神経細胞やグリア細胞のみならず、末梢神経や一般臓器の細胞にも広く出現する神経変性疾患である。成人発症NIIDの大多数は白質脳症(Leukoencephalopathy;LE)を伴う認知症を呈する。近年、診断に皮膚生検が有用であることが報告された。本疾患の病態機序は不明であるものの、組織学的に、NIの多くはアストロサイトに出現し、病巣においてアストロサイトの形態異常やグリオーシス不全が認められることから、アストロサイトの機能障害が疑われている。アストロサイトの活性化や増殖を促進する主要な増殖因子としてTGF-βが知られている。TGF-βシグナル経路は、Smad2/3のリン酸化と核内移行を介して伝達され、Smurf2により抑制的に調節されている。我々はこの経路の障害がアストロサイトの機能異常を招き、本疾患の病態に関与していると推測した。本研究では、LEを伴い中枢神経症候を呈した成人発症NIIDの剖検例5例と生検例1例(With LE群)、および、それらを有さず剖検にて偶発的にNIが認められた3例(Without LE群)の大脳組織と、LEを伴い中枢神経症候を呈し皮膚生検にて成人発症NIIDと診断された7例の皮膚組織を対象として、NIの形態学的特徴とTGF-βシグナル関連蛋白の発現を検討した。その結果、NIは概ね90%がグリア細胞に出現し、その出現頻度はLEの有無に関連しなかった。また、With LE群のNIは、Without LE群では見られない大きなサイズまで幅広く分布していた。さらに、リン酸化Smad2/3の正常な核内の発現は、LEの有無に関わらず、NIを有する細胞で低下や消失していた。また、一部のNIはSmurf2陽性を示し、その陽性率は皮質細胞および脳室上衣細胞のいずれにおいてもWith LE群において有意に高く、皮膚生検例でも同様であった。以上から、NI形成は直接的に細胞障害には結びつかず、病態の進行に伴いその構造や組成が変化すると考えられた。また、TGF-βシグナル経路の障害が組織障害を来すより以前の段階から生じ、一方で、Smurf2の過剰発現がアストロサイトの機能障害やLEの発症に関与している可能性が示唆された。また、皮膚生検組織におけるp62とSmurf2に対する抗体を用いた蛍光免疫二重染色によるNIの共陽性率の測定は本疾患の診断の参考となり得る。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20181002100002&doc_link_id=%2Fdg3nigta%2F2018%2F013203%2F002%2F0083-0092%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2F013203%2F002%2F0083-0092%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • これって神経内科の病気? 整形外科外来に紛れ込む神経疾患の最近の話題

    小野寺 理

    日本整形外科学会雑誌   92 ( 3 )   S619 - S619   2018.3

     More details

    Language:Japanese   Publisher:(公社)日本整形外科学会  

    researchmap

  • 脳小血管病患者でヘテロ接合性に認められたhigh-temperature requirement A serine peptidase 1(HTRA1)変異の病的意義の検討

    上村 昌寛, 小野寺 理

    新潟医学会雑誌   132 ( 3 )   105 - 114   2018.3

     More details

    Language:Japanese   Publisher:新潟医学会  

    High-temperature requirement A serine peptidase 1(HTRA1)変異のホモもしくは複合ヘテロ接合体は遺伝性脳小血管病をおこす。一方、近年、脳小血管病患者においてHTRA1変異のヘテロ接合体が複数例報告された。HTRA1はセリンプロテアーゼであり、3量体となる事でその活性を調節している。筆者らは、HTRA1変異ヘテロ接合体で認められたHTRA1変異の病態機序として、変異型HTRA1が優性阻害効果(dominant negative effects:DN)を示すことを提唱してきた。本研究では、既報の変異型HTRA1のDNの有無を解析し、本仮設を検証した。まず、既報の15種(S121R、A123S、R133G、R166C、R166L、A173P、A173T、S284G、S284R、P285Q、F286V、G295R、A321T、L364P、D450H)の変異型HTRA1の精製蛋白を作成し、カゼインを基質としてプロテアーゼ活性を測定した。その結果、11種(S121R、R166C、R166L、A173P、A173T、S284R、P285Q、F286V、G295R、A321T、L364P)で、野生型HTRA1と比較して有意な低下を認めた。次に、野生型HTRA1と変異型HTRA1を混合しプロテアーゼ活性を測定したところ、5種(R166L、A173P、A173T、S284R、G295R)でDNを認めた。さらに、ゲル濾過クロマトグラフィーにて3量体形成能を解析したところ、DNを認める5種の変異のうち、4種(R166L、A173P、A173T、G295R)の3量体の形成不全を認めた。最後にDNを認めたヘテロ接合体変異例17例とDNを認めないヘテロ接合体変異例9例の臨床像を比較したところ、DNを認める群で症候性脳小血管病の頻度が有意に高かった(76.5% vs 33.3%、p<0.046)。以上の結果から、DNを認める変異型HTRA1は、ヘテロ接合体で症候性脳小血管病の発症に寄与するという仮説が支持された。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20181002100004&doc_link_id=%2Fdg3nigta%2F2018%2F013203%2F004%2F0105-0114%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2F013203%2F004%2F0105-0114%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 長期間精神症状が先行した、PSEN1遺伝子変異を有する早期発症型家族性アルツハイマー病の1剖検例

    竹島 明, 他田 真理, 鈴木 正博, 春日 健作, 池内 健, 小野寺 理, 高橋 均, 柿田 明美, 伊古田 勇人

    信州医学雑誌   66 ( 1 )   110 - 111   2018.2

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • 長期間精神症状が先行した、PSEN1遺伝子変異を有する早期発症型家族性アルツハイマー病の1剖検例

    竹島 明, 他田 真理, 鈴木 正博, 春日 健作, 池内 健, 小野寺 理, 高橋 均, 柿田 明美, 伊古田 勇人

    信州医学雑誌   66 ( 1 )   110 - 111   2018.2

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • 常染色体劣性遺伝性が疑われる若年発症 緩徐進行性小脳失調症の1剖検例

    齋藤 理恵, 他田 真理, 若林 允甫, 小野寺 理, 高橋 均, 池内 健, 柿田 明美, 横尾 英明

    信州医学雑誌   66 ( 1 )   111 - 112   2018.2

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • 常染色体劣性遺伝性が疑われる若年発症 緩徐進行性小脳失調症の1剖検例

    齋藤 理恵, 他田 真理, 若林 允甫, 小野寺 理, 高橋 均, 池内 健, 柿田 明美, 横尾 英明

    信州医学雑誌   66 ( 1 )   111 - 112   2018.2

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • 各種疾患 脳血管障害 脳梗塞に対する低酸素・低糖刺激ミクログリアを用いた新規細胞療法

    金澤 雅人, 高橋 哲哉, 小野寺 理, 下畑 享良

    Annual Review神経   2018   166 - 173   2018.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 通常シーケンスの頭部MRIで側頭極病変を欠いたCADASILの53歳男性例

    椎橋 元, 滝沢 翼, 関 守信, 中原 仁, 伊東 大介, 高橋 愼一, 野崎 洋明, 小野寺 理, 鈴木 則宏

    臨床神経学   58 ( 1 )   54 - 54   2018.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 血液透析療法下で、脳出血発症後に脳浮腫が急速進行した58歳女性例

    大津 裕, 金山 武史, 二宮 格, 石原 智彦, 保坂 聖子, 忰田 亮平, 成田 一衛, 小野寺 理

    臨床神経学   58 ( 1 )   55 - 55   2018.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 通常シーケンスの頭部MRIで側頭極病変を欠いたCADASILの53歳男性例

    椎橋 元, 滝沢 翼, 関 守信, 中原 仁, 伊東 大介, 高橋 愼一, 野崎 洋明, 小野寺 理, 鈴木 則宏

    臨床神経学   58 ( 1 )   54 - 54   2018.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 血液透析療法下で、脳出血発症後に脳浮腫が急速進行した58歳女性例

    大津 裕, 金山 武史, 二宮 格, 石原 智彦, 保坂 聖子, 忰田 亮平, 成田 一衛, 小野寺 理

    臨床神経学   58 ( 1 )   55 - 55   2018.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 各種疾患 脳血管障害 脳梗塞に対する低酸素・低糖刺激ミクログリアを用いた新規細胞療法

    金澤 雅人, 高橋 哲哉, 小野寺 理, 下畑 享良

    Annual Review神経   2018   166 - 173   2018.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • T2<sup>*</sup>強調画像で微小出血を認めず,軟髄膜病変が急速に拡大したアミロイドβ関連血管炎の75歳女性例

    畠野雄也, 須貝章弘, 山岸宅磨, 中島章博, 他田正義, 河内泉, 小野寺理

    臨床神経学(Web)   58 ( 8 )   2018

  • 大脳皮質基底核変性症剖検例における臨床像の解明および臨床診断基準の妥当性検証~多施設共同研究~Japanese validation study of consensus criteria for the diagnosis of corticobasal degeneration~multicenter study~(J-VAC study)

    饗場郁子, 下畑享良, 小野寺理, 池内健, 豊島靖子, 柿田明美, 高橋均, 吉田眞理, 村山繁雄, 中野雄太, 徳丸阿耶, 横田隆徳, 大久保卓哉, 内原俊記, 秋山治彦, 長谷川成人, 矢部一郎, 青木正志, 長谷川隆文, 長谷川一子, 新井哲明, 大島健一, 新里和弘, 横田修, 小森隆司, 若林孝一, 齋藤祐子, 櫻井圭太, 足立正, 瀧川洋史, 中島健二

    神経変性疾患領域における基盤的調査研究 平成29年度 総括・分担研究報告書(Web)   2018

  • プリオン病のサーベイランスと感染予防に関する調査研究:JACOP自然歴調査との統合によるサーベイランスの発展

    水澤英洋, 塚本忠, 三條伸夫, 佐々木秀直, 青木正志, 小野寺理, 田中章景, 道勇学, 望月秀樹, 阿部康二, 村井弘之, 松下拓也, 佐藤克也, 北本哲之, 中村好一, 村山繁雄, 黒岩義之, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 田村智英子, 山田正仁, 桑田一夫

    プリオン病及び遅発性ウイルス感染症に関する調査研究 平成29年度 総括・分担研究報告書(Web)   2018

  • 血管性認知症の再定義(Serine protease HTRA1 deficiency induces arteriopathy in cerebral small vessels)

    加藤 泰介, 関根 有美, 藤田 菜摘, 野崎 洋明, 廣川 祥子, 佐藤 俊哉, 辻 省次, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [1PW21 - 5]   2017.12

     More details

    Language:English   Publisher:生命科学系学会合同年次大会運営事務局  

    researchmap

  • 【CADASILとCARASIL】 CARASILの臨床遺伝学的特徴と分子病態

    酒井 直子, 野崎 洋明, 上村 昌寛, 小野寺 理

    神経内科   87 ( 6 )   638 - 642   2017.12

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 家族性脳小血管病患者で報告された変異型HTRA1蛋白質の機能解析

    上村 昌寛, 野崎 洋明, 加藤 泰介, 小山 哲秀, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [1P - 1241]   2017.12

     More details

    Language:English   Publisher:生命科学系学会合同年次大会運営事務局  

    researchmap

  • 血管性認知症の再定義 脳の小血管におけるセリンプロテアーゼHTRA1欠損は動脈症を誘発する(Serine protease HTRA1 deficiency induces arteriopathy in cerebral small vessels)

    加藤 泰介, 関根 有美, 藤田 菜摘, 野崎 洋明, 廣川 祥子, 佐藤 俊哉, 辻 省次, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [1PW21 - 5]   2017.12

     More details

    Language:English   Publisher:生命科学系学会合同年次大会運営事務局  

    researchmap

  • ALS原因遺伝子TDP-43の点変異によるアレル特異的遺伝子発現の変化

    須貝 章弘, 廣川 祥子, 小山 哲秀, 今野 卓哉, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [3P - 1118]   2017.12

     More details

    Language:Japanese   Publisher:生命科学系学会合同年次大会運営事務局  

    J-GLOBAL

    researchmap

  • 家族性脳小血管病患者で報告された変異型HTRA1蛋白質の機能解析

    上村 昌寛, 野崎 洋明, 加藤 泰介, 小山 哲秀, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [1P - 1241]   2017.12

     More details

    Language:English   Publisher:生命科学系学会合同年次大会運営事務局  

    researchmap

  • 脳梗塞後遺症の機能回復を目指した低酸素低糖刺激保護的ミクログリア細胞療法

    金澤 雅人, 三浦 南, 鳥谷部 真史, 小山 美咲, 畠山 公大, 石川 正典, 中島 孝, 小野寺 理, 高橋 哲哉, 西澤 正豊, 下畑 享良

    脳循環代謝   29 ( 1 )   157 - 157   2017.11

     More details

    Language:Japanese   Publisher:日本脳循環代謝学会  

    researchmap

  • 免疫抑制薬の減量が有効であった中枢神経原発移植後リンパ増殖性疾患の1例

    小出 眞悟, 徳武 孝允, 茂木 崇秀, 笠原 壮, 中川 由紀, 齊藤 和英, 他田 正義, 下畑 享良, 小野寺 理

    神経治療学   34 ( 6 )   S222 - S222   2017.11

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 脳小血管病

    小野寺 理

    神経治療学   34 ( 6 )   S154 - S154   2017.11

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    DOI: 10.15082/jsnt.34.6_S154

    researchmap

  • 酵素補充療法を導入した遅発型ポンペ病兄妹例における治療経験 呼吸機能障害に対する効果の検討

    黒羽 泰子, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 佐藤 晶, 小野寺 理, 小池 亮子

    神経治療学   34 ( 6 )   S204 - S204   2017.11

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 有痛性筋痙攣に対して免疫グロブリン静注療法が有効であった筋萎縮性側索硬化症の1例

    茂木 崇秀, 石原 智彦, 他田 正義, 河内 泉, 下畑 享良, 小野寺 理

    神経治療学   34 ( 6 )   S199 - S199   2017.11

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 酵素補充療法を導入した遅発型ポンペ病兄妹例における治療経験 呼吸機能障害に対する効果の検討

    黒羽 泰子, 長谷川 有香, 谷 卓, 高橋 哲哉, 松原 奈絵, 佐藤 晶, 小野寺 理, 小池 亮子

    神経治療学   34 ( 6 )   S204 - S204   2017.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 脳小血管病

    小野寺 理

    神経治療学   34 ( 6 )   S154 - S154   2017.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 有痛性筋痙攣に対して免疫グロブリン静注療法が有効であった筋萎縮性側索硬化症の1例

    茂木 崇秀, 石原 智彦, 他田 正義, 河内 泉, 下畑 享良, 小野寺 理

    神経治療学   34 ( 6 )   S199 - S199   2017.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 免疫抑制薬の減量が有効であった中枢神経原発移植後リンパ増殖性疾患の1例

    小出 眞悟, 徳武 孝允, 茂木 崇秀, 笠原 壮, 中川 由紀, 齊藤 和英, 他田 正義, 下畑 享良, 小野寺 理

    神経治療学   34 ( 6 )   S222 - S222   2017.11

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • Double inversion recovery MRI in the evaluation of the anterior visual pathway in patients with multiple sclerosis and neuromyelitis optica spectrum disorders

    E. Saji, M. Hokari, A. Yokoseki, T. Wakasugi, F. Yanagimura, K. Yanagawa, M. Nishizawa, O. Onodera, I. Kawachi

    MULTIPLE SCLEROSIS JOURNAL   23   102 - 102   2017.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SAGE PUBLICATIONS LTD  

    Web of Science

    researchmap

  • Dynamics of tissue regulatory T cells in neuromyelitis optica spectrum disorders lesions

    F. Yanagimura, E. Saji, T. Wakasugi, M. Hokari, Y. Toyoshima, A. Kakita, H. Takahashi, M. Nishizawa, O. Onodera, I. Kawachi

    MULTIPLE SCLEROSIS JOURNAL   23   492 - 492   2017.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SAGE PUBLICATIONS LTD  

    Web of Science

    researchmap

  • 意味性認知症の画像所見とバイオマーカーの検討

    徳武 孝允, 春日 健作, 三浦 健, 目崎 直実, 平井 香織, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   590 - 590   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 肥厚性硬膜炎・自己免疫疾患・膠原病 診断基準・重症度分類作成に向けた肥厚性硬膜炎の臨床的・免疫学的解析

    佐治 越爾, 横関 明子, 若杉 尚宏, 柳村 文寛, 穂苅 万李子, 柳川 香織, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   89 - 89   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 臨床ケース 再発性胸腺腫術後に腹壁の難治性疼痛を呈した重症筋無力症の44歳男性例

    山岸 拓磨, 佐治 越爾, 荻根沢 真也, 安藤 昭一郎, 茂木 崇秀, 他田 正義, 河内 泉, 小野寺 理

    神経免疫学   22 ( 1 )   106 - 106   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 急性脳炎・脳症 自己免疫性脳炎の臨床的・免疫学的・放射線学的特徴の解析

    若杉 尚宏, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 柳川 香織, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   102 - 102   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 繰り返しの髄液検査で診断し得た経過3年のクリプトコッカス性髄膜脳炎の1例

    大津 裕, 須貝 章弘, 茂木 崇秀, 若杉 尚宏, 眞島 卓弥, 他田 正義, 下畑 享良, 小野寺 理

    臨床神経学   57 ( 10 )   632 - 632   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 感覚性運動失調型ニューロパチーと鑑別を要した脊椎疾患の2例

    畠野 雄也, 金澤 雅人, 林 秀樹, 青山 あずさ, 須貝 章弘, 徳武 孝允, 下畑 享良, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   11回   102 - 102   2017.10

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    J-GLOBAL

    researchmap

  • CARASIL症候性キャリアの一例

    野崎 洋明, 伊藤 絢子, 阿部 崇, 豊島 靖子, 佐藤 晶, 橋立 英樹, 五十嵐 修一, 高橋 均, 小野寺 理, 柿田 明美

    Dementia Japan   31 ( 4 )   543 - 543   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 血管性認知障害の分子病態と治療 脳小血管病の分子病態 CARASILからのアプローチ

    小野寺 理

    Dementia Japan   31 ( 4 )   498 - 498   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • RVCL関連変異の細胞内局在についての検討

    笠原 杏子, 加藤 泰介, 野崎 洋明, 小山 哲秀, 小野寺 理

    Dementia Japan   31 ( 4 )   572 - 572   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 神経細胞興奮がβ-amyloid precursor protein(APP) processingへ及ぼす影響

    石黒 敬信, 春日 健作, 斎藤 健智, 目崎 直実, 三浦 健, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   560 - 560   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 認知症疾患におけるアルツハイマー病関連脳脊髄液バイオマーカーの解析

    春日 健作, 徳武 孝允, 三浦 健, 目崎 直実, 石黒 敬信, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   610 - 610   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • HDLS患者におけるCSF1R新規ミスセンス変異の同定及び変異CSF1R機能解析

    三浦 健, 目崎 直実, 石黒 敬信, 徳武 孝允, 春日 健作, 今野 卓哉, 野崎 洋明, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   595 - 595   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    J-GLOBAL

    researchmap

  • 意味性認知症の画像所見とバイオマーカーの検討

    徳武 孝允, 春日 健作, 三浦 健, 目崎 直実, 平井 香織, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   590 - 590   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 多系統萎縮症における認知機能低下の予測因子の検討

    畠山 公大, 佐藤 朋江, 高橋 哲哉, 金澤 雅人, 小野寺 理, 西澤 正豊, 下畑 享良

    Dementia Japan   31 ( 4 )   597 - 597   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Lamin B1関連常染色体優性遺伝性白質脳症 コピー数多型と臨床的特徴

    目崎 直実, 三浦 健, 大垣 光太郎, 江里口 誠, 水野 裕理, 小松 研一, 山崎 博輝, 末次 南月, 河尻 澄宏, 山崎 亮, 野崎 洋明, 春日 健作, 大熊 泰之, 吉良 潤一, 原 英夫, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   596 - 596   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • MS・NMO2 視神経脊髄炎における脳室上衣の免疫学的・病理学的検討

    柳村 文寛, 佐治 越爾, 穂苅 万李子, 若杉 尚宏, 豊島 靖子, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   113 - 113   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 臨床ケース 再発性胸腺腫術後に腹壁の難治性疼痛を呈した重症筋無力症の44歳男性例

    山岸 拓磨, 佐治 越爾, 荻根沢 真也, 安藤 昭一郎, 茂木 崇秀, 他田 正義, 河内 泉, 小野寺 理

    神経免疫学   22 ( 1 )   106 - 106   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 急性脳炎・脳症 自己免疫性脳炎の臨床的・免疫学的・放射線学的特徴の解析

    若杉 尚宏, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 柳川 香織, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   102 - 102   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 肥厚性硬膜炎・自己免疫疾患・膠原病 診断基準・重症度分類作成に向けた肥厚性硬膜炎の臨床的・免疫学的解析

    佐治 越爾, 横関 明子, 若杉 尚宏, 柳村 文寛, 穂苅 万李子, 柳川 香織, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   89 - 89   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • HDLS患者におけるCSF1R新規ミスセンス変異の同定及び変異CSF1R機能解析

    三浦 健, 目崎 直実, 石黒 敬信, 徳武 孝允, 春日 健作, 今野 卓哉, 野崎 洋明, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   595 - 595   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    J-GLOBAL

    researchmap

  • 多系統萎縮症における認知機能低下の予測因子の検討

    畠山 公大, 佐藤 朋江, 高橋 哲哉, 金澤 雅人, 小野寺 理, 西澤 正豊, 下畑 享良

    Dementia Japan   31 ( 4 )   597 - 597   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • MS・NMO2 視神経脊髄炎における脳室上衣の免疫学的・病理学的検討

    柳村 文寛, 佐治 越爾, 穂苅 万李子, 若杉 尚宏, 豊島 靖子, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理, 河内 泉

    神経免疫学   22 ( 1 )   113 - 113   2017.10

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • Lamin B1関連常染色体優性遺伝性白質脳症 コピー数多型と臨床的特徴

    目崎 直実, 三浦 健, 大垣 光太郎, 江里口 誠, 水野 裕理, 小松 研一, 山崎 博輝, 末次 南月, 河尻 澄宏, 山崎 亮, 野崎 洋明, 春日 健作, 大熊 泰之, 吉良 潤一, 原 英夫, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   596 - 596   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 認知症疾患におけるアルツハイマー病関連脳脊髄液バイオマーカーの解析

    春日 健作, 徳武 孝允, 三浦 健, 目崎 直実, 石黒 敬信, 小野寺 理, 池内 健

    Dementia Japan   31 ( 4 )   610 - 610   2017.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【脊髄小脳変性症(SCD)-最新診療マニュアル】 治療と介護の現状 パーキンソニズム

    他田 正義, 小野寺 理

    Clinical Neuroscience   35 ( 9 )   1097 - 1100   2017.9

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 脳梗塞後の機能回復を目指したミクログリアによる細胞療法

    金澤 雅人, 高橋 哲哉, 小野寺 理, 下畑 享良

    脳循環代謝   28 ( 2 )   315 - 320   2017.8

     More details

    Language:Japanese   Publisher:日本脳循環代謝学会  

    脳梗塞後遺症の機能を回復させる治療法の確立が望まれている.ミクログリアを保護的ミクログリア(M2)に変化させる低酸素低糖刺激(OGD)の条件を決定し,M2-likeミクログリアを亜急性期に投与することで,脳虚血後の機能予後を改善させることが可能かを検証した.初代ミクログリアの培養上清を試料として,血管内皮増殖因子(VEGF),トランスフォーミング増殖因子(TGF-β),およびマトリックス・メタロプロテナーゼ(MMP)-9活性を測定したところ,18時間のOGD後,M2極性となっていることがわかった.さらに,ラット一過性局所脳虚血モデルに対し,虚血7日後,M2-likeミクログリアを投与したところ,虚血中心の辺縁部におけるVEGF,TGF-β,MMP-9の発現は増加し,さらに同部位の血管新生,ペナンブラにおける軸索伸展は,非投与群と比べて促進され,虚血4週間後の機能を回復させた.OGDによりM2化したミクログリアを用いた細胞療法は,従来にない治療戦略になるものと考えられる.(著者抄録)

    DOI: 10.16977/cbfm.28.2_315

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02631&link_issn=&doc_id=20170911390011&doc_link_id=10.16977%2Fcbfm.28.2_315&url=https%3A%2F%2Fdoi.org%2F10.16977%2Fcbfm.28.2_315&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 【遺伝性脊髄小脳失調症の病態と治療展望】 本邦における遺伝性脊髄小脳変性症の全体像

    他田 正義, 横関 明男, 小野寺 理

    BRAIN and NERVE: 神経研究の進歩   69 ( 8 )   879 - 890   2017.8

     More details

    Language:Japanese   Publisher:(株)医学書院  

    遺伝性脊髄小脳変性症(SCD)は緩徐進行性の運動失調を主症状とする遺伝性神経変性疾患の総称である。優性遺伝性,劣性遺伝性,X染色体連鎖性に大別される。錐体路徴候,錐体外路徴候,末梢神経障害など小脳症候以外の多彩な神経症候を伴うものが多い。本邦では,マシャド・ジョセフ病,脊髄小脳失調症6型(SCA6),SCA31の頻度が高い。診断は遺伝子検査により確定される。遺伝性SCDに対する有効な病態抑止療法はいまだ確立されていない。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04871&link_issn=&doc_id=20170821060003&doc_link_id=40021311545&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40021311545&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Predictors of cognitive impairment in multiple system atrophy

    M. Hatakeyama, T. Sato, T. Takahashi, M. Kanazawa, O. Onodera, M. Nishizawa

    MOVEMENT DISORDERS   32   2017.6

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY  

    Web of Science

    researchmap

  • Progression of milestones by clinical types in progressive supranuclear palsy: a longitudinal observational study of a cohort of patients with PSP/CBD (the JALPAC project)

    I. Aiba, T. Ikeuchi, H. Takigawa, T. Shimohata, T. Tokuda, M. Morita, O. Onodera, S. Murayama, K. Hasegawa, K. Nakashima

    MOVEMENT DISORDERS   32   2017.6

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY  

    Web of Science

    researchmap

  • 遺伝性脳血管障害 CARASIL:HTRA1活性の低下と脳小血管病

    小野寺 理

    日本動脈硬化学会総会プログラム・抄録集   49回   145 - 145   2017.6

     More details

    Language:Japanese   Publisher:(一社)日本動脈硬化学会  

    researchmap

  • 単下肢失調を呈した多発性硬化症の30歳女性例

    井上 佳奈, 大原 浩司, 茂木 崇秀, 佐治 越爾, 他田 正義, 河内 泉, 下畑 享良, 小野寺 理

    臨床神経学   57 ( 6 )   335 - 335   2017.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CADASIL姉弟剖検例の臨床病理所見

    齋藤 理恵, 豊島 靖子, 鈴木 正博, 田中 政春, 野崎 洋明, 小野寺 理, 高橋 均, 柿田 明美

    新潟医学会雑誌   131 ( 5 )   313 - 314   2017.5

  • 【多系統萎縮症の新しい道】 [第3部]過去10年の多系統萎縮症の薬の開発について

    小野寺 理

    難病と在宅ケア   23 ( 2 )   14 - 17   2017.5

  • Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats

    M. Kanazawa, M. Miura, M. Toriyabe, M. Koyama, M. Hatakeyama, M. Ishikawa, T. Nakajima, O. Onodera, T. Takahashi, M. Nishizawa, T. Shimohata

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM   37   262 - 263   2017.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SAGE PUBLICATIONS INC  

    Web of Science

    researchmap

  • 【遺伝が関与する認知症-主な認知症と遺伝子との関連について】 脳血管性認知症

    小野寺 理

    認知症の最新医療   7 ( 2 )   69 - 73   2017.4

     More details

    Language:Japanese   Publisher:(有)フジメディカル出版  

    脳小血管の機能がわかるにつれ、脳小血管を首座とする疾患を脳小血管病と呼ぶようになってきている。脳小血管は、排泄機構や動的な血流再配分機能を持つことが指摘されており、脳小血管病は脳血管性認知症の背景疾患ともいえる。遺伝性の脳小血管病の検討から基底膜にかかわる疾患は出血性病変を伴い、一方、平滑筋細胞が関与する疾患では認知症や歩行障害が主体となることが示唆される。孤発性の脳血管性認知症でも、平滑筋細胞層の消失が指摘されており、このことは、動的な血流再配分機能の重要性を示唆している。今後は、脳小血管の動的な機能と認知症の関連に注目し、診断方法と介入方法の検討が期待される。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J05808&link_issn=&doc_id=20170502050004&doc_link_id=%2Fal1demud%2F2017%2F000702%2F005%2F0069-0073%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fal1demud%2F2017%2F000702%2F005%2F0069-0073%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • TDP-43 G357S変異を伴った家族性筋萎縮性側索硬化症の70歳男性例

    茂木 崇秀, 石原 智彦, 横関 明男, 他田 正義, 下畑 享良, 小野寺 理

    臨床神経学   57 ( 4 )   192 - 192   2017.4

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【PSPとCBD-その共通点と相違点】 進行性核上性麻痺(PSP) 小脳型進行性核上性麻痺(PSP-C)

    金澤 雅人, 下畑 享良, 小野寺 理

    Clinical Neuroscience   35 ( 3 )   299 - 301   2017.3

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 遺伝子診断における問題を考える

    小野寺 理

    日本遺伝看護学会誌   15 ( 2 )   52 - 56   2017.3

     More details

    Language:Japanese   Publisher:日本遺伝看護学会  

    researchmap

  • CARASILでのヘテロ接合体におけるHTRA1変異の異なる発症機序(Distinct mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL)

    野崎 洋明, 加藤 泰介, 水田 依久子, 水野 敏樹, 西澤 正豊, 小野寺 理

    日本内科学会雑誌   106 ( Suppl. )   184 - 184   2017.2

     More details

    Language:English   Publisher:(一社)日本内科学会  

    researchmap

  • [PRES: Posterior Reversible Encephalopathy Syndrome].

    Kouichirou Okamoto, Kunio Motohashi, Hidemoto Fujiwara, Tomohiko Ishihara, Itaru Ninomiya, Osamu Onodera, Yukihiko Fujii

    Brain and nerve = Shinkei kenkyu no shinpo   69 ( 2 )   129 - 141   2017.2

     More details

    Language:Japanese   Publisher:(株)医学書院  

    Posterior reversible encephalopathy syndrome (PRES) is suggested in patients with acute neurological symptoms in the appropriate clinical context, including acute hypertension, blood pressure fluctuations, renal failure, blood transfusion, immunosuppression, autoimmune disorders, and eclampsia. PRES is a clinical syndrome, and refers to a disorder with reversible subcortical vasogenic brain edema caused by endothelial dysfunction, predominantly involving the bilateral parieto-occipital regions. Although the clinical course and prognosis are favorable in most cases, intracranial hemorrhage and/or restricted diffusion similar to acute infarction could be seen in some lesions on brain magnetic resonance imaging (MRI). The spinal cord may be involved in some patients with posterior fossa lesions. Understanding the pathophysiology of PRES is helpful in making the correct early diagnosis and selecting appropriate therapies to improve its clinical course and outcome. Differentiation of PRES from strokes is critical in the setting of a neurological emergency.

    DOI: 10.11477/mf.1416200653

    PubMed

    researchmap

  • [PRES: Posterior Reversible Encephalopathy Syndrome].

    Kouichirou Okamoto, Kunio Motohashi, Hidemoto Fujiwara, Tomohiko Ishihara, Itaru Ninomiya, Osamu Onodera, Yukihiko Fujii

    Brain and nerve = Shinkei kenkyu no shinpo   69 ( 2 )   129 - 141   2017.2

     More details

    Language:Japanese   Publisher:(株)医学書院  

    Posterior reversible encephalopathy syndrome (PRES) is suggested in patients with acute neurological symptoms in the appropriate clinical context, including acute hypertension, blood pressure fluctuations, renal failure, blood transfusion, immunosuppression, autoimmune disorders, and eclampsia. PRES is a clinical syndrome, and refers to a disorder with reversible subcortical vasogenic brain edema caused by endothelial dysfunction, predominantly involving the bilateral parieto-occipital regions. Although the clinical course and prognosis are favorable in most cases, intracranial hemorrhage and/or restricted diffusion similar to acute infarction could be seen in some lesions on brain magnetic resonance imaging (MRI). The spinal cord may be involved in some patients with posterior fossa lesions. Understanding the pathophysiology of PRES is helpful in making the correct early diagnosis and selecting appropriate therapies to improve its clinical course and outcome. Differentiation of PRES from strokes is critical in the setting of a neurological emergency.

    DOI: 10.11477/mf.1416200653

    PubMed

    researchmap

  • Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

    Masahiro Uemura, Hiroaki Nozaki, Osamu Onodera

    Brain and Nerve   69 ( 1 )   25 - 33   2017.1

     More details

    Language:Japanese   Publisher:Igaku-Shoin Ltd  

    Cerebral small vessel disease (CSVD) is frequently observed among the elderly and is known to cause dementia and gait disturbance associated with white matter lesions, lacunar infarcts, and cerebral hemorrhage. Molecular mechanistic studies promise to provide new insights into the pathogenesis of hereditary CSVD. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is one of the hereditary CSVDs caused by a mutation in the hightemperature requirement serine peptidase A1 (HTRA1) gene. The loss of HTRA1 protease activity increases signaling via transforming growth factor (TGF)β, thereby resulting in CARASIL. Although the CARASIL has been characterized by juvenile onset alopecia and spondylosis deformans, these features are not always observed in individuals with an HTRA1 mutation. Moreover, some HTRA1 mutations cause CSVD in heterozygous states. Therefore, the clinical features of CSVD resulting from an HTRA1 mutation extend to patients with CSVD alone or to those with dominantly inherited CSVD.

    Scopus

    PubMed

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04871&link_issn=&doc_id=20170203260006&doc_link_id=10.11477%2Fmf.1416200631&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1416200631&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 【脳血管病変と脳疾患】 遺伝性脳小血管病 matrisomeから見た分子病態

    野崎 洋明, 小野寺 理

    神経治療学   34 ( 1 )   9 - 12   2017.1

  • エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立に関する研究 肥厚性硬膜炎の診断基準・重症度分類に関する研究

    河内泉, 西澤正豊, 佐治越爾, 横関明子, 柳村文寛, 若杉尚宏, 荒川武蔵, 柳川香織, 穂苅万李子, 小野寺理, 豊島靖子, 柿田明美, 高橋均

    エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立 平成28年度 総括・分担研究報告書(Web)   50‐51 (WEB ONLY)   2017

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • プリオン病のサーベイランスと感染予防に関する調査研究 サーベイランスデータに基づくわが国のプリオン病の疫学像(1999‐2016年データ)

    水澤英洋, 中村好一, 山田正仁, 齊藤延人, 北本哲之, 金谷泰宏, 村山繁雄, 佐藤克也, 原田雅史, 太組一朗, 佐々木秀直, 青木正志, 小野寺理, 田中章景, 犬塚貴, 望月秀樹, 阿部康二, 村井弘之, 古賀雄一, 黒岩義之, 桑田一夫, 三條伸夫, 塚本忠

    プリオン病のサーベイランスと感染予防に関する調査研究 平成28年度 総括・分担研究報告書(Web)   25‐40 (WEB ONLY)   2017

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • プリオン病及び遅発性ウイルス感染症に関する調査研究 プリオン病のサーベイランス,感染予防,および臨床研究コンソーシアムJACOPの推進

    水澤英洋, 塚本忠, 三條伸夫, 森若文雄, 佐々木秀直, 青木正志, 西澤正豊, 小野寺理, 田中章景, 犬塚貴, 武田雅俊, 望月秀樹, 阿部康二, 村井弘之, 佐藤克也, 北本哲之, 中村好一, 村山繁雄, 黒岩義之, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 田村智英子, 山田正仁

    プリオン病及び遅発性ウイルス感染症に関する調査研究 平成26-28年度 総合研究報告書(Web)   72‐77 (WEB ONLY)   2017

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • プリオン病及び遅発性ウイルス感染症に関する調査研究 プリオン病のサーベイランスと感染予防に関する調査研究:JACOP自然歴調査との統合によるサーベイランスの発展

    水澤英洋, 塚本忠, 三條伸夫, 佐々木秀直, 青木正志, 小野寺理, 田中章景, 犬塚貴, 望月秀樹, 阿部康二, 村井弘之, 佐藤克也, 北本哲之, 中村好一, 村山繁雄, 黒岩義之, 原田雅史, 齊藤延人, 太組一朗, 金谷泰宏, 田村智英子, 山田正仁, 桑田一夫

    プリオン病及び遅発性ウイルス感染症に関する調査研究 平成28年度 総括・分担研究報告書(Web)   15‐17 (WEB ONLY)   2017

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立に関する研究 多発性硬化症と視神経脊髄炎の臨床経過と炎症・神経変性機構に関する研究

    河内泉, 穂苅万李子, 佐治越爾, 柳村文寛, 若杉尚宏, 横関明子, 荒川武蔵, 柳川香織, 小野寺理, 豊島靖子, 柿田明美, 高橋均, 西澤正豊

    エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立 平成28年度 総括・分担研究報告書(Web)   39‐40 (WEB ONLY)   2017

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 神経変性疾患領域における基盤的調査研究 大脳皮質基底核変性症剖検例における臨床像の解明および臨床診断基準の妥当性検証~多施設共同研究~

    饗場郁子, 下畑享良, 小野寺理, 池内健, 豊島靖子, 柿田明美, 高橋均, 吉田眞理, 村山繁雄, 中野雄太, 徳丸阿耶, 横田隆徳, 大久保卓哉, 内原俊記, 秋山治彦, 長谷川成人, 矢部一郎, 青木正志, 長谷川隆文, 長谷川一子, 新井哲明, 大島健一, 新里和弘, 横田修, 小森隆司, 若林孝一, 齋藤祐子, 櫻井圭太, 足立正, 瀧川洋史, 中島健二

    神経変性疾患領域における基盤的調査研究 平成28年度 総括・分担研究報告書(Web)   2017

  • リツキシマブが有効であったMAG抗体関連神経障害の67歳男性例

    小出 眞悟, 西田 茉那, 斎藤 奈つみ, 笠原 壮, 二宮 格, 堅田 慎一, 小野寺 理

    臨床神経学   56 ( 12 )   876 - 876   2016.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Toxicity of dipeptide repeat proteins in C9 ALS/FTD model fly

    Morio Ueyama, Taro Ishiguro, Tania F. Gendron, Nobuhiro Fujikake, Takuya Konno, Akihide Koyama, Osamu Onodera, Kinya Ishikawa, Keiji Wada, Leonard Petrucelli, Yoshitaka Nagai

    GENES & GENETIC SYSTEMS   91 ( 6 )   365 - 365   2016.12

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:GENETICS SOC JAPAN  

    Web of Science

    researchmap

  • 脳虚血に対する成長因子プログラニュリンの神経保護メカニズムの検討

    鳥谷部 真史, 小野寺 理

    新潟医学会雑誌   130 ( 12 )   679 - 690   2016.12

     More details

    Language:Japanese   Publisher:新潟医学会  

    【序文】プログラニュリン(PGRN)は神経栄養活性を有する成長因子である。PGRN遺伝子変異は、核蛋白TAR DNA結合蛋白-43(TDP-43)が神経細胞内に蓄積する前頭側頭型変性症を引き起こすことが知られている。脳虚血に関しても、ラット血栓塞栓モデルにて、血栓溶解薬組織プラスミノーゲンアクティベーター(t-PA)と組み替えPGRN蛋白の併用投与は、脳梗塞体積の減少、出血量の減少をもたらし、PGRNが神経細胞を含む多面的な脳保護作用を有することが明らかになった。しかしPGRNによる神経細胞保護作用の機序と、TDP-43への影響については十分には明らかにされていない。今回、PGRNがTDP-43の限定分解および細胞質内異常局在を抑制することで、虚血性神経細胞障害に対し保護作用を示すという仮説を立て、検証を行った。【材料と方法】PGRNノックアウトマウスと、野生型マウスの一過性脳虚血モデルにおいて、虚血24時間後のTDP-43の細胞内局在を免疫染色にて比較した。次にラット血栓塞栓モデルにて、虚血4時間後に、血栓溶解薬(t-PA)と組み換えマウスPGRNないし対照蛋白(IgG)の静注を行い、虚血24時間後に免疫ブロットにて活性型カスパーゼ-3、全長型および切断されたTDP-43の発現の比較を行った。さらに種の異なる、組み換えヒトPGRN投与による脳梗塞抑制効果について、ラット血栓塞栓モデルを用いて検討を行った。【結果】PGRNノックアウトマウスでは、野生型と比較して、虚血後のTDP-43の細胞質異常局在を認める神経細胞の頻度が多かった(P&lt;0.001)。また血栓塞栓モデルでは、PGRN投与群は対照群と比して、全長型TDP-43の虚血後の減少は抑制され(P&lt;0.05)、さらに活性型カスパーゼ-3発現が抑制された(P&lt;0.05)。ラット血栓塞栓モデルにおいて、ヒト組み換えPGRN投与は、対照群と比較して、脳梗塞体積を縮小した(P&lt;0.05)。【考察】脳虚血に対するPGRNの神経細胞保護作用の機序としては、カスパーゼ-3活性化を抑制し、全長型TDP-43の限定分解およびTDP-43の異常細胞質内局在を抑制し、TDP-43の機能を保つことが関与する可能性が示唆された。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00990&link_issn=&doc_id=20170410150005&doc_link_id=%2Fdg3nigta%2F2016%2F013012%2F005%2F0679-0690%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2016%2F013012%2F005%2F0679-0690%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 脊髄小脳変性症に対するバレニクリン酒石酸塩の治療効果の検討

    他田 正義, 徳永 純, 徳武 孝允, 石原 智彦, 野崎 洋明, 関根 有美, 堅田 慎一, 横関 明男, 小野寺 理, 西澤 正豊

    臨床神経学   56 ( Suppl. )   S488 - S488   2016.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミンタンパク質オリゴマ化阻害剤のQAI1は疾患修飾性の治療効果をもたらす(QAI1, a polyglutamine protein oligomerization inhibitor, exerts diseasemodifying therapeutic effect)

    皆川 栄子, Popiel H. Akiko, 他田 正義, 高橋 俊昭, 山根 宏志, 齊藤 勇二, 鈴木 マリ, 岡本 佑馬, 渡瀬 啓, 足立 弘明, 勝野 雅央, 祖父江 元, 戸田 達史, 和田 圭司, 小野寺 理, 永井 義隆

    臨床神経学   56 ( Suppl. )   S306 - S306   2016.12

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • SMN遺伝子欠失は日本における下位運動ニューロン疾患の発症リスクと関連する(SMN gene deletion is associated with developing risk of lower motor neuron disease in Japan)

    豊田 佐織, 石原 智彦, 小山 哲秀, 西澤 正豊, 小野寺 理

    臨床神経学   56 ( Suppl. )   S230 - S230   2016.12

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • 成人発症白質脳症におけるLaminB1関連常染色体優性白質脳症 遺伝子変異と臨床的特徴

    目崎 直実, 三浦 健, 野崎 洋明, 大垣 光太郎, 河尻 澄宏, 大熊 泰之, 小野 南月, 原 英夫, 春日 健作, 小野寺 理, 西澤 正豊, 池内 健

    臨床神経学   56 ( Suppl. )   S444 - S444   2016.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脳小血管病の分子病態機序 CARASILからのアプローチ

    小野寺 理

    臨床神経学   56 ( Suppl. )   S50 - S50   2016.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • リツキシマブが有効であったMAG抗体関連神経障害の67歳男性例

    小出 眞悟, 西田 茉那, 斎藤 奈つみ, 笠原 壮, 二宮 格, 堅田 慎一, 小野寺 理

    臨床神経学   56 ( 12 )   876 - 876   2016.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 意味性認知症の臨床症状・画像的特徴・脳脊髄液バイオマーカーの検討

    徳武 孝允, 春日 健作, 三浦 健, 目崎 直実, 平井 香織, 西澤 正豊, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   583 - 583   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Barthel IndexならびにPSPRS-Jによる進行性核上性麻痺症例のADL評価に関する検討

    瀧川 洋史, 池内 健, 森田 光哉, 饗場 郁子, 小野寺 理, 下畑 享良, 徳田 隆彦, 村山 繁雄, 中島 健二, JALPAC研究グループ

    神経治療学   33 ( 5 )   S229 - S229   2016.10

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 脊髄小脳変性症に対するバレニクリン酒石酸塩の治療効果の検討

    他田 正義, 堅田 慎一, 横関 明男, 小野寺 理, 西澤 正豊

    神経治療学   33 ( 5 )   S247 - S247   2016.10

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 病理診断されたGlobular Glial Tauopathyの臨床的特徴 自験2例と既報39例のまとめ

    三浦 健, 目崎 直実, 三瓶 一弘, 青木 賢樹, 竹内 亮子, 田中 英智, 豊島 靖子, 柿田 明美, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   542 - 542   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • LaminB1関連常染色体優性遺伝性白質脳症 遺伝子重複と臨床的特徴

    目崎 直実, 三浦 健, 野崎 洋明, 大垣 光太郎, 河尻 澄宏, 大熊 泰之, 小野 南月, 原 英夫, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   541 - 541   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • ヘテロ接合体でCARASILを呈するHTRA1変異の特有の機序(Distinct mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL)

    野崎 洋明, 加藤 泰介, 水田 依久子, 野田 智子, 宮崎 一秀, 吉田 眞理, 西澤 正豊, 水野 敏樹, 小野寺 理

    Dementia Japan   30 ( 4 )   533 - 533   2016.10

     More details

    Language:English   Publisher:(一社)日本認知症学会  

    researchmap

  • 地域総合病院通院患者における透析療法と認知機能スケールとの関連 PROST

    渡邊 裕美, 北村 香織, 若杉 三奈子, 横関 明男, 三瓶 一弘, 小野寺 理, 池内 健, 百都 健, 成田 一衛, 遠藤 直人

    Dementia Japan   30 ( 4 )   550 - 550   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Barthel IndexならびにPSPRS-Jによる進行性核上性麻痺症例のADL評価に関する検討

    瀧川 洋史, 池内 健, 森田 光哉, 饗場 郁子, 小野寺 理, 下畑 享良, 徳田 隆彦, 村山 繁雄, 中島 健二, JALPAC研究グループ

    神経治療学   33 ( 5 )   S229 - S229   2016.10

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • LaminB1関連常染色体優性遺伝性白質脳症 遺伝子重複と臨床的特徴

    目崎 直実, 三浦 健, 野崎 洋明, 大垣 光太郎, 河尻 澄宏, 大熊 泰之, 小野 南月, 原 英夫, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   541 - 541   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Distinct mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL(和訳中)

    野崎 洋明, 加藤 泰介, 水田 依久子, 野田 智子, 宮崎 一秀, 吉田 眞理, 西澤 正豊, 水野 敏樹, 小野寺 理

    Dementia Japan   30 ( 4 )   533 - 533   2016.10

     More details

    Language:English   Publisher:(一社)日本認知症学会  

    researchmap

  • 病理計断されたGlobular Glial Tauopathyの臨床的特徴 自験2例と既報39例のまとめ

    三浦 健, 目崎 直実, 三瓶 一弘, 青木 賢樹, 竹内 亮子, 田中 英智, 豊島 靖子, 柿田 明美, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   542 - 542   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 意味性認知症の臨床症状・画像的特徴・脳脊髄液バイオマーカーの検討

    徳武 孝允, 春日 健作, 三浦 健, 目崎 直実, 平井 香織, 西澤 正豊, 小野寺 理, 池内 健

    Dementia Japan   30 ( 4 )   583 - 583   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 地域総合病院通院患者における透析療法と認知機能スケールとの関連 PROST

    渡邊 裕美, 北村 香織, 若杉 三奈子, 横関 明男, 三瓶 一弘, 小野寺 理, 池内 健, 百都 健, 成田 一衛, 遠藤 直人

    Dementia Japan   30 ( 4 )   550 - 550   2016.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 脊髄小脳変性症に対するバレニクリン酒石酸塩の治療効果の検討

    他田 正義, 堅田 慎一, 横関 明男, 小野寺 理, 西澤 正豊

    神経治療学   33 ( 5 )   S247 - S247   2016.10

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 重症帯状疱疹のためフィンゴリモド一時中断に伴いbreakthrough disease様の進展を来した多発性硬化症の一例

    大津 裕, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 若杉 尚宏, 柳川 香織, 西澤 正豊, 河内 泉, 小野寺 理

    神経免疫学   21 ( 1 )   108 - 108   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • Neuromyelitis optica脳病変における神経放射線学的・神経病理学的特徴

    穂苅 万李子, 佐治 越爾, 柳村 文寛, 柳川 香織, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   124 - 124   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 視神経脊髄炎におけるtissue Tregs動態の検討

    柳村 文寛, 佐治 越爾, 穂苅 万李子, 柳川 香織, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   123 - 123   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 眼窩炎症性偽腫瘍における髄液サイトカイン・ケモカインの検討

    佐治 越爾, 西田 茉那, 柳村 文寛, 穂苅 万李子, 若杉 尚宏, 柳川 香織, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   139 - 139   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 慢性腎臓病急性増悪時に突然の意識障害とびまん性の脳幹病変を呈した44歳女性例

    齋藤 奈つみ, 石黒 舞乃, 佐治 越爾, 下畑 享良, 小野寺 理, 羽深 将人, 細島 康宏, 山本 卓, 成田 一衛

    臨床神経学   56 ( 9 )   646 - 646   2016.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Severe neurodegeneration and unique dynamics of aquaporin-4 on astrocytes in the anterior visual pathway of neuromyelitis optica.

    I. Kawachi, M. Hokari, A. Yokoseki, M. Arakawa, E. Saji, K. Yanagawa, F. Yanagimura, Y. Toyoshima, A. Kakita, H. Takahashi, O. Onodera, M. Nishizawa

    MULTIPLE SCLEROSIS JOURNAL   22   24 - 24   2016.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SAGE PUBLICATIONS LTD  

    Web of Science

    researchmap

  • 慢性腎臓病急性増悪時に突然の意識障害とびまん性の脳幹病変を呈した44歳女性例

    齋藤奈つみ, 石黒舞乃, 佐治越爾, 下畑享良, 小野寺理, 羽深将人, 細島康宏, 山本卓, 成田一衛

    臨床神経学(Web)   56 ( 9 )   646(J‐STAGE) - 646   2016.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    J-GLOBAL

    researchmap

  • Neuromyelitis optica脳病変における神経放射線学的・神経病理学的特徴

    穂苅 万李子, 佐治 越爾, 柳村 文寛, 柳川 香織, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   124 - 124   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 視神経脊髄炎におけるtissue Tregs動態の検討

    柳村 文寛, 佐治 越爾, 穂苅 万李子, 柳川 香織, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   123 - 123   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 重症帯状疱疹のためフィンゴリモド一時中断に伴いbreakthrough disease様の進展を来した多発性硬化症の一例

    大津 裕, 佐治 越爾, 柳村 文寛, 穂苅 万李子, 若杉 尚宏, 柳川 香織, 西澤 正豊, 河内 泉, 小野寺 理

    神経免疫学   21 ( 1 )   108 - 108   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 眼窩炎症性偽腫瘍における髄液サイトカイン・ケモカインの検討

    佐治 越爾, 西田 茉那, 柳村 文寛, 穂苅 万李子, 若杉 尚宏, 柳川 香織, 小野寺 理, 西澤 正豊, 河内 泉

    神経免疫学   21 ( 1 )   139 - 139   2016.9

     More details

    Language:Japanese   Publisher:日本神経免疫学会  

    researchmap

  • 慢性腎臓病急性増悪時に突然の意識障害とびまん性の脳幹病変を呈した44歳女性例

    齋藤 奈つみ, 石黒 舞乃, 佐治 越爾, 下畑 享良, 小野寺 理, 羽深 将人, 細島 康宏, 山本 卓, 成田 一衛

    臨床神経学   56 ( 9 )   646 - 646   2016.9

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 浸透圧性脱髄症候群の機序とその臨床症状

    小野寺 理

    日本腎臓学会誌   58 ( 6 )   749 - 749   2016.8

     More details

    Language:Japanese   Publisher:(一社)日本腎臓学会  

    researchmap

  • 遺伝を理解する、説明する

    小野寺 理

    日本遺伝看護学会誌   15 ( 1 )   28 - 28   2016.8

     More details

    Language:Japanese   Publisher:日本遺伝看護学会  

    researchmap

  • 認知症の新しい臨床学、病態学

    小野寺 理

    新潟県医師会報   ( 796 )   2 - 6   2016.7

     More details

    Language:Japanese   Publisher:新潟県医師会  

    認知症は、その臨床症状からは生化学的背景を正確に予測できないという臨床診断の限界が明らかになっている。この点から、認知症を含めた神経変性疾患の臨床的な理解・診断に、大きな変革のうねりが押し寄せてきている。さらに、ヒトの脳機能には、神経細胞のみではなく、グリア細胞、さらに微小血管系の関与が重要であることも明らかとなり、その病態学の理解にも大きな変革が押し寄せている。これらの認知症の新しい側面について、臨床学、病態学、認知症の制御に分けて述べた。

    researchmap

  • A longitudinal observational study of a cohort of patients with PSP/CBD: The JALPAC project

    T. Tokuda, T. Ikeuchi, H. Takigawa, I. Aiba, T. Shimohata, M. Morita, O. Onodera, S. Murayama, K. Nakashima

    MOVEMENT DISORDERS   31   S59 - S59   2016.6

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL  

    Web of Science

    researchmap

  • 脳小血管の最新の知見から見る脳血管性認知症の再定義

    小野寺 理

    日本早期認知症学会誌   9 ( 1 )   17 - 21   2016.6

     More details

    Language:Japanese   Publisher:日本早期認知症学会  

    近年、脳の微小循環の病態学が注目され、ここを首座とする疾患群を脳小血管病(SVD)と称し、これによる脳血管性認知症が認識されるようになってきた。しかし、その治療方法、診断方法は確立しておらず、脳微小循環系の最新の研究成果を還元したSVDの理解と脳血管性認知症の再定義が求められている。脳血管の解剖、真の小血管:毛細血管の解剖、壁細胞と小血管機能、SVDでの小血管病理像について述べた。

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J06098&link_issn=&doc_id=20160801470003&doc_link_id=%2Fer4ninti%2F2016%2F000901%2F007%2F0017-0021%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer4ninti%2F2016%2F000901%2F007%2F0017-0021%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Proposed Diagnostic Criteria for Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia

    Takuya Konno, Kunihiro Yoshida, Toshiki Mizuno, Toshitaka Kawarai, Masayoshi Tada, Hiroaki Nozaki, Shu-Ichi Ikeda, Masatoyo Nishizawa, Osamu Onodera, Zbigniew Wszolek, Takeshi Ikeuchi

    NEUROLOGY   86   2016.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • 小脳症状をどう捉えるか 小脳機能に基づく小脳症状の再構築

    他田 正義, 西澤 正豊, 小野寺 理

    MDSJ Letters   9 ( 1 )   4 - 5   2016.4

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    ヒトが身体を動かす時、脳はかなり複雑な計算問題を解く必要があり、内部モデルを必要とする。内部モデルとは、脳の外に存在する対象の入出力特性をまねることができる脳内の神経回路のことで、順モデルと逆モデルの2種類がある。小脳機能をより直接的に評価する上で、内部モデルを構成する神経回路に基づいて小脳症状を理解することは重要である。小脳の機能と内部モデル、小脳神経回路に基づく小脳症状の新しい捉え方について概説した。

    researchmap

  • 【認知症】 病態生理 周皮細胞と認知症

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    最新医学   71 ( 3月増刊 )   544 - 549   2016.3

     More details

    Language:Japanese   Publisher:(株)最新医学社  

    周皮細胞は主に毛細血管レベルに分布し,微小循環の調節に重要な役割を持つ細胞の1つである.近年,周皮細胞が血液脳関門(BBB)の維持や脳血流調節に関与しており,その機能低下が認知症の病態に影響を及ぼす可能性が指摘されている.このことは,周皮細胞機能の維持や改善が,認知症治療の新たな標的と成りうることを示唆している.本稿では,最近の知見を交えながら,周皮細胞の機能や認知症病態との関連について述べる.(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00516&link_issn=&doc_id=20160407220009&doc_link_id=issn%3D0370-8241%26volume%3D71%26issue%3D3%26spage%3D544&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0370-8241%26volume%3D71%26issue%3D3%26spage%3D544&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • 【脳卒中はこう診る-新ガイドラインで何が変わったか】 押さえておくべき脳卒中のトピックス 遺伝性脳小血管病を診断する

    野崎 洋明, 西澤 正豊, 小野寺 理

    Medicina   53 ( 2 )   335 - 338   2016.2

     More details

    Language:Japanese   Publisher:(株)医学書院  

    <ポイント>脳小血管病(CSVD)とは,脳小血管を病変の首座とする疾患群を指す用語である.大脳白質病変があり,ラクナ梗塞,脳出血,微小出血のいずれかを伴い,頭部MRAで50%を超える主幹動脈狭窄がなければ,病的意義のあるCSVDが存在する.CSVD患者を診療する際,次のいずれかを1つでも満たす場合は遺伝性CSVDの可能性を考える.(1)脳卒中について2親等以内の家族歴がある,(2)60歳未満の発症である,(3)高血圧症がない.脳卒中の発症が小児期か成人期か,白質病変が両側性かつびまん性かどうか,神経外臓器の合併症があるかどうかの情報だけでも,遺伝性CSVDを起こす疾患を絞り込める.(著者抄録)

    researchmap

  • ライソゾーム病(ファブリー病含む)に関する調査研究 副腎白質ジストロフィーの多彩な表現型を規定する遺伝的修飾因子の探索研究

    辻省次, 松川敬志, 三井純, 石浦浩之, AHSAN Budrul, 吉村淳, 土井晃一郎, 鈴木康之, 下澤伸行, 小野寺理, 西澤正豊, 森下真一

    ライソゾーム病(ファブリ病含む)に関する調査研究班 平成27年度 総括・分担研究年度終了報告書   84‐85   2016

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 神経変性疾患領域における基盤的調査研究 大脳皮質基底核変性症剖検例における臨床像の解明および臨床診断基準の妥当性検証~多施設共同研究~

    饗場郁子, 下畑享良, 小野寺理, 池内健, 豊島靖子, 柿田明美, 高橋均, 吉田眞理, 村山繁雄, 中野雄太, 徳丸阿耶, 横田隆徳, 大久保卓哉, 内原俊記, 秋山治彦, 長谷川成人, 矢部一郎, 青木正志, 長谷川隆文, 長谷川一子, 新井哲明, 大島健一, 新里和弘, 横田修, 小森隆司, 若林孝一, 齋藤祐子, 櫻井圭太, 足立正, 瀧川洋史, 中島健二

    神経変性疾患領域における基盤的調査研究 平成27年度 総括・分担研究報告書   108‐111   2016

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • Barthel IndexならびにPSPRS-Jによる進行性核上性麻痺症例のADL評価に関する検討

    瀧川洋史, 池内健, 森田光哉, 饗場郁子, 小野寺理, 下畑享良, 徳田隆彦, 村山繁雄, 中島健二

    神経治療学(Web)   33 ( 5 )   2016

  • C9ALS/FTDモデルショウジョウバエにおけるジペプチドリピートタンパク質の毒性

    上山盛夫, 上山盛夫, 石黒太郎, 石黒太郎, 石黒太郎, TANIA Gendron, 藤掛伸宏, 今野卓哉, 小山哲秀, 小野寺理, 石川欣也, 和田圭司, LEONARD Petrucelli, 永井義隆, 永井義隆

    日本遺伝学会大会プログラム・予稿集   88th   2016

  • TDP-43はリボソーム蛋白質のmRNAを輸送する

    長野 清一, 廣川 祥子, 西澤 正豊, 崎村 建司, 小野寺 理, 荒木 敏之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [4T15L - 05(3P1235)]   2015.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • Establishment of a novel animal model of ALS/FTD expressing G4C2 repeat RNA in Drosophila

    Morio Ueyama, Taro Ishiguro, Nobuhiro Fujikake, Takuya Konno, Akihide Koyama, Osamu Onodera, Keiji Wada, Yoshitaka Nagai

    GENES & GENETIC SYSTEMS   90 ( 6 )   366 - 366   2015.12

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:GENETICS SOC JAPAN  

    Web of Science

    researchmap

  • 【小脳の最新知見-基礎研究と臨床の最前線】 小脳の病態 小脳疾患の診療の最前線 劣性遺伝性脊髄小脳変性症

    他田 正義, 小野寺 理

    医学のあゆみ   255 ( 10 )   1040 - 1046   2015.12

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    劣性遺伝性脊髄小脳変性症(AR-SCD)は、緩徐進行性の運動失調を中核症状とする常染色体劣性遺伝性の神経変性疾患である。原因の異なる多数の疾患を含み、臨床・遺伝学的スペクトラムは多彩である。わが国における脊髄小脳失調症のなかでAR-SCDの占める割合は約1.8%と推定されている。疾患内訳は人種により大きく異なり、欧米ではFriedreich失調症が多数を占めるのに対し、わが国では眼球運動失行と低アルブミン血症を伴う早発型失調症が最多と推定されている。臨床病型は、(1)後根神経節・脊髄後索の変性を伴う脊髄型、(2)小脳性運動失調を主体とし感覚運動性ニューロパチーを含む種々の神経症候を伴う小脳型、および(3)小脳性運動失調以外の神経症候を伴わない純粋小脳型、に大別される。病態は疾患によりさまざまであるが、ミトコンドリア機能障害、代謝障害、核酸品質管理機構の障害、蛋白品質管理機構の障害などの関与が想定されている。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00060&link_issn=&doc_id=20151208010019&doc_link_id=%2Faa7ayuma%2F2015%2F025510%2F020%2F1040-1046%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2015%2F025510%2F020%2F1040-1046%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • CARASILにおけるMRI変化の進行のパターンと影響因子(The pattern and the influencing factors of progression of MRI changes in CARASIL)

    野崎 洋明, 関根 有美, 福武 敏夫, 西本 祥仁, 下江 豊, 白田 明子, 柳川 宗平, 平山 幹生, 田村 正人, 西澤 正豊, 小野寺 理

    臨床神経学   55 ( Suppl. )   S362 - S362   2015.12

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • Kinectを用いた3次元歩行解析システムによる小脳性歩行障害の解析

    他田 正義, 徳永 純, 小野寺 理, 西澤 正豊

    臨床神経学   55 ( Suppl. )   S318 - S318   2015.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CARASILの脳MRI所見から重症度を評価する判定システム(A rating system for assessing severity from brain MRI findings for CARASIL)

    関根 有美, 野崎 洋明, 福武 敏夫, 西本 祥仁, 下江 豊, 白田 明子, 柳川 宗平, 平山 幹生, 田村 正人, 西澤 正豊, 小野寺 理

    臨床神経学   55 ( Suppl. )   S362 - S362   2015.12

     More details

    Language:English   Publisher:(一社)日本神経学会  

    researchmap

  • 遺伝性神経疾患からのTDP-43病理の意義

    小野寺 理

    臨床神経学   55 ( Suppl. )   S132 - S132   2015.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 佐渡島における脳血管障害の危険因子についての検討 PROST研究から

    赤岩 靖久, 横関 明男, 小野寺 理, 西澤 正豊

    臨床神経学   55 ( Suppl. )   S243 - S243   2015.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 軸索スフェロイド形成を伴うびまん性白質脳症(HDLS)の診断基準案の策定

    今野 卓哉, 吉田 邦広, 水野 敏樹, 瓦井 俊孝, 他田 正義, 勇 亜衣子, 野崎 洋明, 池田 修一, 西澤 正豊, 小野寺 理, 池内 健

    臨床神経学   55 ( Suppl. )   S200 - S200   2015.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【脳血管からみた認知症の病態】 脳の微小循環維持シグナルと血管性認知症 CARASILからのアプローチ

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    Dementia Japan   29 ( 4 )   534 - 540   2015.10

     More details

    Language:Japanese   Publisher:日本認知症学会  

    researchmap

  • 劣性軸索型および混合型Charcot-Marie-Tooth病における新規病因遺伝子COX6A1の同定

    早坂 清, 田宮 元, 牧野 悟士, 沼倉 周彦, 林 真貴子, 阿部 暁子, 植木 優夫, 田中 敦, 他田 正義, 小野寺 理

    日本先天代謝異常学会雑誌   31   149 - 149   2015.10

     More details

    Language:Japanese   Publisher:日本先天代謝異常学会  

    researchmap

  • 小脳は何をしているのか? 基礎から病態まで 小脳症状をどう捉えるか 小脳機能に基づく小脳症状の再構築

    他田 正義, 小野寺 理, 西澤 正豊

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   9回   63 - 63   2015.10

     More details

    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 地域総合病院通院患者の血清高感度C反応性蛋白(CRP)と認知機能スケールとの関連 PROST

    渡邊 裕美, 北村 香織, 中村 和利, 横関 明男, 三瓶 一弘, 小野寺 理, 池内 健, 百都 健, 成田 一衛, 遠藤 直人

    Dementia Japan   29 ( 3 )   368 - 368   2015.9

     More details

    Language:Japanese   Publisher:日本認知症学会  

    researchmap

  • 脊髄小脳失調症6型の多施設共同自然史研究

    安井 建一, 矢部 一郎, 吉田 邦広, 金井 数明, 澤井 摂, 新井 公人, 伊藤 瑞規, 小野寺 理, 足立 芳樹, 佐々木 秀直, 桑原 聡, 祖父江 元, 西澤 正豊, 中島 健二

    神経治療学   32 ( 5 )   767 - 767   2015.9

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 早期認知症の臨床と病理 早期介入に向けた脳血管性認知症のパラダイムシフト

    小野寺 理

    日本早期認知症学会誌   8 ( 2 )   157 - 157   2015.8

     More details

    Language:Japanese   Publisher:日本早期認知症学会  

    researchmap

  • ALSにおけるGEM小体とU snRNA異常 RNA代謝異常は運動神経変性の共通した病態機序となるか

    小池 佑佳, 石原 智彦, 西澤 正豊, 小野寺 理

    神経内科   83 ( 2 )   175 - 184   2015.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    機能性RNAの中の代表的なものに、転移RNA、リボソームRNAなどがある。これらは、それぞれ翻訳において重要な役割を有する。この機能性RNAの一種にuridine rich small nuclear RNA(UsnRNA)がある。細胞内のmRNAや機能性RNAの量的、質的な多様性、恒常性のことをribostasisと称し、筋萎縮性側索硬化症(ALS)の病態機序との関連が注目されている。RNA代謝の中で、UsnRNAおよびUsnRNAの成熟に関わる核内の構造物であるGemini of coiled bodyとALSとの関連について最新の知見を述べた。

    researchmap

  • 骨代謝に影響を及ぼす薬物に関する応用薬理学的研究の最近の話題について 糖尿病治療薬の骨代謝に与える影響について

    若林 広行, 神田 循吉, 出雲 信夫, 小林 芳子, 島倉 剛俊, 山本 智章, 小野寺 憲治

    応用薬理   89 ( 1-2 )   48 - 48   2015.8

     More details

    Language:Japanese   Publisher:応用薬理研究会  

    researchmap

  • 【神経変性疾患への新しい視点-プリオン仮説】ポリグルタミン病 ポリグルタミン病とは

    山田 舞乃, 他田 正義, 西澤 正豊, 小野寺 理

    Clinical Neuroscience   33 ( 3 )   327 - 331   2015.3

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 骨代謝への還元型コエンザイムQ10の作用

    神田 循吉, 出雲 信夫, 小林 芳子, 島倉 剛俊, 山本 智章, 朝倉 俊成, 松本 洋介, 安島 力, 小野寺 憲治, 若林 広行

    日本薬学会年会要旨集   135年会 ( 3 )   136 - 136   2015.3

     More details

    Language:Japanese   Publisher:(公社)日本薬学会  

    researchmap

  • 末梢神経障害と後索変性を伴った中年期発症の脊髄小脳変性症の1剖検例

    齋藤 理恵, 他田 真理, 谷 卓, 小池 亮子, 五十嵐 修一, 山崎 元義, 小野寺 理, 西澤 正豊, 高橋 均, 柿田 明美

    信州医学雑誌   63 ( 1 )   70 - 71   2015.2

     More details

    Language:Japanese   Publisher:信州医学会  

    researchmap

  • Emerging molecular mechanism for cerebral small vessel disease: Lessons from hereditary small vessel disease

    Osamu Onodera, Yumi Sekine, Taisuke Kato, Akihide Koyama, Hiroaki Nozaki, Masatoyo Nishizawa

    NEUROLOGY AND CLINICAL NEUROSCIENCE   3 ( 1 )   7 - 13   2015.1

     More details

    Language:English   Publishing type:Book review, literature introduction, etc.   Publisher:WILEY  

    Cerebral small vessel disease is a common disorder in the elderly. The findings of hereditary small vessel disease studies clearly show that small vessel diseases have a distinct molecular pathway that is different from that in large vessels. However, the anatomical and functional heterogeneity of the cerebral small vessel system makes it difficult to understand the concept and molecular mechanism for small vessel disease. The purpose of this review is to explain the heterogeneity of small vessels and the importance of the components of the capillary system in the pathogenesis of cerebral small vessel disease. Although traditional investigations have focused more attention on the arteriole, the most functional part of small arteries is the capillary. Therefore, the capillary might play an important role in the pathogenesis of small vessel disease. In the capillary, pericytes and astrocytes are unique components with marked diversity. However, the molecular signature and function of pericytes remain unknown. Furthermore, the morphology and molecular signature of astrocytes in the cortex and white matter are quite different. Therefore, the mechanism of small vessel disease is not simple, and must be investigated considering the diversities of small vessels. In the capillary, cross-talk between cell components exists. Among these cell signaling pathways, recent findings on the gene responsible for hereditary small vessel disease show that transforming growth factor-beta and platelet-derived growth factor-beta could contribute to the molecular pathogenesis of small vessel disease. These findings provide useful information for the development of a new therapeutic strategy for small vessel disease.

    DOI: 10.1111/ncn3.134

    Web of Science

    researchmap

  • 神経変性疾患領域における基盤的調査研究 わが国におけるCBD診断基準の検証~多施設共同研究の提案~

    饗場郁子, 下畑享良, 小野寺理, 池内健, 高橋均, 吉田眞理, 村山繁雄, 横田隆徳, 内原俊記, 青木正志, 横田修, 新井哲明, 秋山治彦, 大島健一, 新里和弘

    神経変性疾患領域における基盤的調査研究 平成26年度 総括・分担研究報告書   2015

  • G4C2リピートRNAを発現する新規ALS/FTDモデルショウジョウバエの樹立

    上山盛夫, 石黒太郎, 石黒太郎, 藤掛伸宏, 今野卓哉, 小山哲秀, 小野寺理, 和田圭司, 永井義隆

    日本遺伝学会大会プログラム・予稿集   87th   2015

  • 異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 ALSではいつ細胞障害が始まるのか?TDP-43陽性封入体との関係

    小野寺理, 須貝章弘, 小山哲秀, 加藤泰介, 志賀篤, 今野卓哉, 小山美咲, 石原智彦, 西澤正豊

    異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 平成26年度 総括・分担研究報告書   2015

  • Establishment of a novel animal model of AILS expressing GGGGCC repeat RNA in Drosophila

    Morio Ueyama, Taro Ishiguro, Nobuhiro Fujikake, Takuya Konno, Akihide Koyama, Osamu Onodera, Keiji Wada, Yoshitaka Nagai

    GENES & GENETIC SYSTEMS   89 ( 6 )   334 - 334   2014.12

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:GENETICS SOC JAPAN  

    Web of Science

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLS Microgliaの組織学的異常

    他田 真理, 今野 卓哉, 他田 正義, 岡崎 健一, 荒川 武蔵, 伊東 恭子, 山本 徹, 横尾 英明, 吉倉 延亮, 石原 健司, 豊島 靖子, 小野寺 理, 西澤 正豊, 池内 健, 高橋 均, 柿田 明美

    臨床神経学   54 ( Suppl. )   S214 - S214   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症のTDP-43大脳皮質組織像の多様性 臨床病理および生化学的解析

    竹内 亮子, 他田 真理, 志賀 篤, 今野 卓哉, 豊島 靖子, 小野寺 理, 西澤 正豊, 柿田 明美, 高橋 均

    臨床神経学   54 ( Suppl. )   S200 - S200   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43の新展開 ALSにおけるspliceosome異常

    石原 智彦, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊

    臨床神経学   54 ( 12 )   1155 - 1157   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    TDP-43はRNA代謝に関連する核内蛋白である。その機能低下によるRNA代謝異常が、代表的な成人運動ニューロン疾患である筋萎縮性側索硬化症(Amyotrophic lateral sclerosis;ALS)病態機序の一つとして提唱されている。われわれはALS罹患神経組織において、TDP-43機能低下に由来した、核内小体の一種GEM小体数および機能性RNA蛋白複合体minor spliceosomesの発現低下がみられる事を報告した。同様の現象は小児運動ニューロン疾患である脊髄性筋無力症(spinal muscular atrophy)でもみとめられることから、運動ニューロン疾患における選択的神経変性において重要な役割をはたしている可能性がある。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01550&link_issn=&doc_id=20150320290069&doc_link_id=10011038607&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10011038607&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • HDLSはCSF-1Rの機能喪失で生じる シグナル伝達障害とハプロ不全

    勇 亜衣子, 今野 卓哉, 他田 正義, 他田 真理, 小山 哲秀, 野崎 洋明, 金田 大太, 田代 裕一, 山本 徹, 高橋 均, 西澤 正豊, 小野寺 理, 柿田 明美, 池内 健

    臨床神経学   54 ( Suppl. )   S8 - S8   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TGFβ1過剰発現マウスは脳小血管壁細胞の異常をきたす

    関根 有美, 加藤 泰介, 野崎 洋明, 廣川 祥子, 佐藤 俊哉, 志賀 篤, 笹岡 敏邦, 西澤 正豊, 小野寺 理

    臨床神経学   54 ( Suppl. )   S5 - S5   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALSでのStasimonヒトホモログmRNAのスプライシング異常の検討

    石原 智彦, 志賀 篤, 小山 哲秀, 柿田 明美, 西澤 正豊, 高橋 均, 小野寺 理

    臨床神経学   54 ( Suppl. )   S99 - S99   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • SCARB2変異を認めた進行性ミオクローヌスてんかん2剖検例の臨床病理・生化学的解析

    他田 正義, 付 永娟, 会田 泉, 他田 真理, 武田 茂樹, 豊島 靖子, 中島 孝, 内藤 明彦, 高橋 均, 小野寺 理, 西澤 正豊

    臨床神経学   54 ( Suppl. )   S68 - S68   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS関連TARDBP遺伝子変異は自身の選択的スプライシングに影響をおよぼすか?

    今野 卓哉, 小山 哲秀, 逸見 文昭, 小山 美咲, 須貝 章弘, 加藤 泰介, 石原 智彦, 西澤 正豊, 小野寺 理

    臨床神経学   54 ( Suppl. )   S200 - S200   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43発現低下時におけるミトコンドリア・ダイナミクスの検討

    伊藤 岳, 小山 哲秀, 有泉 優子, 西澤 正豊, 小野寺 理

    臨床神経学   54 ( Suppl. )   S200 - S200   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 核内TDP-43減少は細胞質内TDP-43 mRNA増加をもたらす

    須貝 章弘, 小山 哲秀, 加藤 泰介, 今野 卓哉, 石原 智彦, 西澤 正豊, 小野寺 理

    臨床神経学   54 ( Suppl. )   S62 - S62   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • iPatax 小脳性運動失調の新たな定量評価法

    徳永 純, 他田 正義, 永井 貴大, 小野寺 理, 西澤 正豊

    臨床神経学   54 ( Suppl. )   S32 - S32   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • DCTN1依存的輸送の障害はTDP-43のオリゴマー形成を促進する

    藤掛 伸宏, 木村 展之, 長野 清一, 斉藤 勇二, 横関 明男, 小野寺 理, 和田 圭司, 永井 義隆

    臨床神経学   54 ( Suppl. )   S62 - S62   2014.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Features of Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

    Hiroaki Nozaki, Masatoyo Nishizawa, Osamu Onodera

    STROKE   45 ( 11 )   3447 - 3453   2014.11

     More details

    Language:English   Publishing type:Book review, literature introduction, etc.   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1161/STROKEAHA.114.004236

    Web of Science

    researchmap

  • 軸索スフェロイド形成を伴うびまん性白質脳症(HDLS)の診断基準案の策定

    今野 卓哉, 他田 正儀, 吉田 邦広, 水野 敏樹, 野崎 洋明, 池田 修一, 西澤 正豊, 小野寺 理, 池内 健

    Dementia Japan   28 ( 4 )   510 - 510   2014.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【最新臨床脳卒中学[下]-最新の診断と治療-】血管性認知症 遺伝性血管性認知症の診断と治療 CADASILとCARASILについて

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    日本臨床   72 ( 増刊7 最新臨床脳卒中学(下) )   619 - 623   2014.10

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 遺伝性血管性認知症からみた認知症の分子機構 脳の微小循環維持シグナルと血管性認知症 遺伝性脳小血管病から

    小野寺 理

    Dementia Japan   28 ( 4 )   429 - 429   2014.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 微小管依存的TDP-43輸送の障害はオリゴマー形成を促進し神経変性を惹き起こす

    永井 義隆, 藤掛 伸宏, 木村 展之, 長野 清一, 斉藤 勇二, 小野寺 理, 和田 圭司

    Dementia Japan   28 ( 4 )   474 - 474   2014.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【神経細胞変性のメカニズム】炎症と神経変性

    伊藤 岳, 西澤 正豊, 小野寺 理

    Brain Medical   26 ( 3 )   259 - 263   2014.10

     More details

    Language:Japanese   Publisher:(株)メディカルレビュー社  

    神経変性疾患において、非自律性神経細胞死という概念が注目されている。TDP-43やアミロイドβなどの内因性蛋白質の異常な蓄積が神経細胞そのものに毒性を示すのではなく、神経細胞周囲の環境に働きかけ、ミクログリアを活性化することで神経炎症を引き起こし、グリオーシスおよび神経細胞脱落を引き起こすという考え方である。神経変性疾患の病態機序解明に向け、神経炎症という視点からの知見が徐々に集まってきている。(著者抄録)

    researchmap

  • HTRA1変異ヘテロ接合者における脳小血管病の発症機序

    野崎 洋明, 加藤 泰介, 齊藤 洋兵, 小山 哲秀, 西澤 正豊, 小野寺 理

    Dementia Japan   28 ( 4 )   475 - 475   2014.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Update in amyotrophic lateral sclerosis: an experience from Japan

    O. Onodera, M. Nishizawa, H. Takahashi

    BRAIN PATHOLOGY   24   3 - 3   2014.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL  

    Web of Science

    researchmap

  • 痙性歩行としびれ感に、バクロフェン髄注療法が著効したAdrenomyeloneuropathyの1例

    黒羽 泰子, 長谷川 有香, 谷 卓, 小野寺 理, 松原 奈絵, 小池 亮子

    神経治療学   31 ( 5 )   623 - 623   2014.9

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 【脳卒中と遺伝子Update】CARASILの新しいトピックス

    野崎 洋明, 西澤 正豊, 小野寺 理

    分子脳血管病   13 ( 2 )   179 - 181   2014.7

     More details

    Language:Japanese   Publisher:(株)先端医学社  

    CARASILはアジアに特異的な稀少疾患と考えられてきたが、遺伝子検査による確定診断によって、アジア以外の地域からも報告され、症候性キャリアが存在する可能性も指摘されるようになった。本稿では、これらCARASILの新しいトピックスについて概説する。(著者抄録)

    researchmap

  • 【最新臨床脳卒中学[上]-最新の診断と治療-】病態生理 CADASIL、CARASILの分子病態機序

    関根 有美, 野崎 洋明, 西澤 正豊, 小野寺 理

    日本臨床   72 ( 増刊5 最新臨床脳卒中学(上) )   148 - 152   2014.7

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • Val263Glyミスセンス変異を認めた眼球運動失行と低アルブミン血症を伴う早期発症型失調症(EAOH)の1例

    坂本 光弘, 川上 暢子, 小松 研一, 石川 奈々, 川村 眞弓, 横関 明男, 小野寺 理, 西澤 正豊

    臨床神経学   54 ( 7 )   605 - 605   2014.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    J-GLOBAL

    researchmap

  • 還元型コエンザイムQ10の骨質改善効果

    若林 広行, 出雲 信夫, 小林 芳子, 島倉 剛俊, 山本 智章, 小野寺 憲治

    日本抗加齢医学会総会プログラム・抄録集   14回   362 - 362   2014.6

     More details

    Language:Japanese   Publisher:(一社)日本抗加齢医学会  

    researchmap

  • 【脳血管構築の特異性と認知症】CADASIL、CARASILの病態機序

    手塚 敏之, 西澤 正豊, 野崎 洋明, 小野寺 理

    血管医学   15 ( 1 )   51 - 58   2014.5

     More details

    Language:Japanese   Publisher:(株)メディカルレビュー社  

    血管性認知症は頻度の高い疾患であるばかりではなく、早期から陽性症状や運動機能障害を呈するため、本人・介護者の負担が著しい。血管性認知症はその病態が複雑で、アルツハイマー病を併発する患者も多いため、病態研究がなかなか進まなかった。しかし、近年、遺伝子解析の技術が進展し、複数の遺伝性血管病の原因遺伝子が同定されたことを契機に、飛躍的にその分子病態が明らかになってきている。本稿では、血管性認知症のうち、虚血性白質病変と多発性ラクナ梗塞を呈するBinswanger病のモデルとなる遺伝性脳小血管病CADASIL/CARASILの分子病態機序に焦点を当てて、解説する。(著者抄録)

    researchmap

  • 【医学・医療のいまがわかるキーワード2014】神経内科 脳小血管病

    小野寺 理

    医学のあゆみ   249 ( 5 )   436 - 436   2014.5

  • 進化する脊髄小脳変性症治療 新たなステージへ 脊髄小脳変性症の治療薬開発に向けて 本邦の治験の歴史から学ぶ

    小野寺 理

    神経治療学   31 ( 3 )   313 - 316   2014.5

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • 【神経症候群(第2版)-その他の神経疾患を含めて-】変性疾患 運動ニューロン疾患 筋萎縮性側索硬化症 遺伝性ALS ALS10(TARDBP遺伝子変異によるALS)

    酒井 直子, 石原 智彦, 小野寺 理, 西澤 正豊

    日本臨床   別冊 ( 神経症候群II )   491 - 495   2014.3

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 【神経症候群(第2版)-その他の神経疾患を含めて-】変性疾患 脊髄小脳変性症 劣性遺伝性脊髄小脳変性症 眼球運動失行と低アルブミン血症を伴う早発型失調症

    横関 明男, 西澤 正豊, 小野寺 理

    日本臨床   別冊 ( 神経症候群II )   385 - 388   2014.3

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 【血管性認知症の最先端】脳小血管の多様性と病態 遺伝性疾患からのレッスン

    小野寺 理

    Dementia Japan   28 ( 1 )   68 - 76   2014.1

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • GGGGCCリピートRNAを発現する新規ALSモデルショウジョウバエの樹立と病態解析

    上山盛夫, 石黒太郎, 藤掛伸宏, 今野卓哉, 小山哲秀, 小野寺理, 和田圭司, 永井義隆

    日本遺伝学会大会プログラム・予稿集   86th   2014

  • 異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 C9ORF72変異を有する日本人ALSの一剖検例

    高橋均, 今野卓哉, 他田真理, 志賀篤, 西澤正豊, 小野寺理, 柿田明美

    異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 平成25年度 総括・分担研究報告書   2014

  • 神経変性疾患に関する調査研究 筋萎縮性側索硬化症の大脳皮質におけるTDP-43組織像の多様性の検討:臨床病理,および生化学的解析

    高橋均, 竹内亮子, 竹内亮子, 他田真理, 志賀篤, 今野卓哉, 豊島靖子, 小野寺理, 西澤正豊, 柿田明美

    神経変性疾患に関する調査研究 平成25年度 総括・分担研究報告書   2014

  • 異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 TDP-43量は自己mRNAのpolyA選択,スプライシング,核貯留の協働により制御される

    須貝章弘, 小山哲秀, 加藤泰介, 志賀篤, 今野卓哉, 小山美咲, 石原智彦, 西澤正豊, 小野寺理

    異常タンパク伝播仮説に基づく神経疾患の画期的治療法の開発 平成25年度 総括・分担研究報告書   2014

  • 神経変性疾患に関する調査研究 TDP-43 mRNAのポリA選択とスプライシングを介した自己蛋白量の制御機構

    小野寺理, 須貝章弘, 小山哲秀, 加藤泰介, 志賀篤, 今野卓哉, 小山美咲, 石原智彦, 西澤正豊

    神経変性疾患に関する調査研究 平成25年度 総括・分担研究報告書   2014

  • TDP-43のRNA制御機構からのALS病態機序の解明

    小野寺 理

    上原記念生命科学財団研究報告集   27   1 - 4   2013.12

     More details

    Language:Japanese   Publisher:(公財)上原記念生命科学財団  

    TAR-DNA binding protein(TDP-43)のRNA制御機構からの筋萎縮性側索硬化症病態機序について検討した。TDP-43は、エクソン6内のスプライシングを介したナンセンス依存性mRNA分解機構によってmRNA量を調整した。TDP-43は複数のpolyA結合部位を有し、少なくとも4ヶ所のpolyA結合部位を持つことが判明した。TDP-43の過剰存在下では、より遠位のpolyA結合部位を使用し、TDP-43のpolyA(+)mRNAが多量に核内に蓄積することが示された。特にそれは遠位のpolyA結合部位を利用する物に強かった。TDP-43の増加は遠位部のpolyA結合部位を利用するTDP-43mRNAの増加をもたらし、このmRNAは核内に貯留する傾向を認めた。mRNAの翻訳には、細胞質への移動が必要で、この機構も、TDP-43の自己調節機能の一端を担っていると想定した。

    researchmap

  • 【神経症候群(第2版)-その他の神経疾患を含めて-】血管障害 その他 遺伝性脳小血管病 COL4A1-related disorder

    関根 有美, 野崎 洋明, 西澤 正豊, 小野寺 理

    日本臨床   別冊 ( 神経症候群I )   314 - 318   2013.12

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 【神経症候群(第2版)-その他の神経疾患を含めて-】血管障害 その他 遺伝性脳小血管病 Retinal vasculopathy with cerebral leukodystrophy(RVCL)

    須貝 章弘, 西澤 正豊, 小野寺 理

    日本臨床   別冊 ( 神経症候群I )   312 - 313   2013.12

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • DCTN1依存的輸送の障害によりTDP-43発現ショウジョウバエの神経変性は増悪する

    藤掛 伸宏, 木村 展之, 長野 清一, 斉藤 勇二, 横関 明男, 小野寺 理, 和田 圭司, 永井 義隆

    臨床神経学   53 ( 12 )   1534 - 1534   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 小脳性運動失調を伴う進行性核上性麻痺の病初期臨床像の検討

    金澤 雅人, 下畑 享良, 他田 真理, 小野寺 理, 高橋 均, 西澤 正豊

    臨床神経学   53 ( 12 )   1467 - 1467   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 等速反復運動の速度変動に着目した小脳性運動失調の新たな定量評価法

    徳永 純, 他田 正義, 永井 貴大, 小野寺 理, 西澤 正豊

    臨床神経学   53 ( 12 )   1467 - 1467   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS患者神経組織におけるU12 snRNAの減少とスプライシング異常

    石原 智彦, 志賀 篤, 有泉 優子, 横関 明男, 譚 春鳳, 柿田 明美, 西澤 正豊, 高橋 均, 小野寺 理

    臨床神経学   53 ( 12 )   1496 - 1496   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 周皮細胞被覆率の解析による脳小血管障害評価法の検討

    関根 有美, 加藤 泰介, 野崎 洋明, 廣川 祥子, 佐藤 俊哉, 志賀 篤, 横山 峯介, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 12 )   1477 - 1477   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43量はTDP-43に惹起される自己mRNAのスプライシングで制御される

    須貝 章弘, 小山 哲秀, 今野 卓哉, 加藤 泰介, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 12 )   1411 - 1411   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLSにおけるCSF1Rシグナル伝達異常の解析

    今野 卓哉, 他田 正義, 小山 哲秀, 他田 真理, 荒川 武蔵, 野崎 洋明, 針谷 康夫, 西宮 仁, 松永 晶子, 米田 誠, 吉倉 延亮, 犬塚 貴, 石原 健司, 河村 満, 高橋 均, 小野寺 理, 西澤 正豊, 池内 健

    臨床神経学   53 ( 12 )   1529 - 1529   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 人工制限酵素による内在性TDP-43遺伝子改変と筋萎縮性側索硬化症モデルへの応用

    佐藤 俊哉, 小田 佳奈子, 酒井 清子, 廣川 祥子, 永田 史也, 前田 宜俊, 藤澤 信義, 西澤 正豊, 小野寺 理, 横山 峯介

    臨床神経学   53 ( 12 )   1500 - 1500   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症におけるGemini of coiled bodyの減少

    有泉 優子, 石原 智彦, 横関 明男, 譚 春鳳, 三木 ゆかり, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 12 )   1497 - 1497   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLSの臨床・遺伝学的解析

    他田 正義, 今野 卓哉, 他田 真理, 荒川 武蔵, 小山 哲秀, 野崎 洋明, 針谷 康夫, 西宮 仁, 松永 晶子, 米田 誠, 吉倉 延亮, 犬塚 貴, 石原 健司, 河村 満, 高橋 均, 小野寺 理, 西澤 正豊, 池内 健

    臨床神経学   53 ( 12 )   1529 - 1529   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLS Microgliaの組織学的解析

    他田 真理, 今野 卓哉, 他田 正義, 岡崎 健一, 荒川 武蔵, 横尾 英明, 伊東 恭子, 吉倉 延亮, 豊島 靖子, 小野寺 理, 西澤 正豊, 池内 健, 高橋 均, 柿田 明美

    臨床神経学   53 ( 12 )   1529 - 1529   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症の脊髄前角細胞におけるCajal小体数の減少

    横関 明男, 譚 春鳳, 石原 智彦, 志賀 篤, 小山 哲秀, 佐藤 達哉, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 12 )   1568 - 1568   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Dominant negative効果をもつ変異型HTRA1はヘテロ接合体でも脳小血管病を引き起こす

    野崎 洋明, 斉藤 洋平, 二本松 萌, 小山 哲秀, 加藤 泰介, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 12 )   1540 - 1540   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症の大脳皮質におけるTDP-43の組織学的および生化学的解析

    竹内 亮子, 志賀 篤, 他田 真理, 今野 卓哉, 豊島 靖子, 柿田 明美, 小野寺 理, 西澤 正豊, 高橋 均

    臨床神経学   53 ( 12 )   1535 - 1535   2013.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 運動ニューロン疾患の遺伝学 Update TDP-43時代のALS病態研究の最前線

    小野寺 理

    臨床神経学   53 ( 11 )   1077 - 1079   2013.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    TDP-43病態において、その蛋白特性と量の制御機構が重要である。蛋白特性としては易凝集性、プリオン様ドメインの存在が特徴である。また疾患関連変異型TDP-43でも安定性の増加や易凝集性の亢進が報告されたが、必ずしも一定しない。一方、量については、TDP-43の量の異常が細胞障害性を示し、その量は自己調節機構により厳密に管理されていることが明らかとなった。TDP-43の機能は、ストレス顆粒との関連、RNAへの直接作用、GEM小体との関連とそれによるU12型のスプライシング異常が唱えられている。これらの機能異常のいずれが真にALSの病態に関与しているか解明が待たれる。(著者抄録)

    DOI: 10.5692/clinicalneurol.53.1077

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01550&link_issn=&doc_id=20140331470059&doc_link_id=10.5692%2Fclinicalneurol.53.1077&url=https%3A%2F%2Fdoi.org%2F10.5692%2Fclinicalneurol.53.1077&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 還元型コエンザイムQ10の長期投与による骨代謝への影響

    神田 循吉, 今井 健太, 小林 芳子, 出雲 信夫, 島倉 剛俊, 山本 智章, 小野寺 憲治, 若林 広行

    日本補完代替医療学会学術集会プログラム・抄録集   16回   66 - 66   2013.11

     More details

    Language:Japanese   Publisher:日本補完代替医療学会  

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLSの臨床・画像・遺伝学的解析

    他田 正義, 今野 卓哉, 他田 真理, 小山 哲秀, 野崎 洋明, 高橋 均, 西澤 正豊, 小野寺 理, 柿田 明美, 池内 健

    Dementia Japan   27 ( 4 )   490 - 490   2013.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 神経軸索スフェロイドを伴う白質脳症HDLSの病態解析 ハプロ不全とCSF1Rシグナル障害

    今野 卓哉, 他田 正義, 他田 真理, 小山 哲秀, 野崎 洋明, 高橋 均, 西澤 正豊, 小野寺 理, 柿田 明美, 池内 健

    Dementia Japan   27 ( 4 )   491 - 491   2013.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    J-GLOBAL

    researchmap

  • 進化する脊髄小脳変性症治療 新たなステージへ 脊髄小脳変性症の治療薬開発に向けて 本邦の治験の歴史から学ぶ

    小野寺 理

    神経治療学   30 ( 5 )   629 - 629   2013.9

     More details

    Language:Japanese   Publisher:(一社)日本神経治療学会  

    researchmap

  • HDLS(hereditary diffuse leukoencephalopathy with spheroids)のMRI所見

    今野 卓哉, 須貝 章弘, 西澤 正豊, 他田 正義, 小野寺 理, 他田 真理, 野崎 洋明, 小山 哲秀, 池内 健

    新潟医学会雑誌   127 ( 6 )   334 - 334   2013.6

  • CARASILのMRI所見

    野崎 洋明, 関根 有美, 西澤 正豊, 小野寺 理, 福武 敏夫, 下江 豊, 平山 幹夫, 柳川 宗平, 西本 祐仁

    新潟医学会雑誌   127 ( 6 )   333 - 334   2013.6

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 【小脳の神経学】 治療研究に向けた小脳機能評価法の将来

    徳永 純, 他田 正義, 永井 貴大, 西澤 正豊, 小野寺 理

    神経内科   78 ( 6 )   687 - 694   2013.6

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 6 CARASILのMRI所見(Ⅰ.一般演題, 第67回新潟画像医学研究会)

    野崎 洋明, 関根 有美, 西澤 正豊, 小野寺 理, 福武 敏夫, 下江 豊, 平山 幹夫, 柳川 宗平, 西本 祥仁

    新潟医学会雑誌   127 ( 6 )   333 - 334   2013.6

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2014056865

  • 【神経軸索spheroidを伴う遺伝性白質脳症(HDLS)】 遺伝性脳小血管病とHDLS

    他田 正義, 今野 卓哉, 西澤 正豊, 池内 健, 小野寺 理

    神経内科   78 ( 4 )   388 - 395   2013.4

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 遺伝性脳小血管病研究の現況と展望

    野崎 洋明, 西澤 正豊, 小野寺 理

    日本臨床   71 ( 3 )   545 - 554   2013.3

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    近年、脳小血管病により認知機能や運動機能の低下をきたすことが明らかになり、本症を管理し進行を予防することが重要な課題となっている。しかし、危険因子である高血圧に対する介入以外に有効な方法が提案されていない。そのため、分子病態機序に基づいた新たな治療法の開発が期待されている。脳小血管の構造について述べ、次に単一遺伝子病として原因遺伝子が判明している遺伝性脳小血管病の研究の現況について概説した。

    researchmap

  • Hereditary diffuse leukoencephalopathy with spheroids(HDLS)の臨床・病理・遺伝学的特徴

    他田 正義, 今野 卓哉, 他田 真理, 荒川 武蔵, 高橋 均, 小野寺 理, 西澤 正豊, 池内 健

    日本内科学会雑誌   102 ( Suppl. )   236 - 236   2013.2

     More details

    Language:Japanese   Publisher:(一社)日本内科学会  

    researchmap

  • 神経症状の進行した副腎白質ジストロフィーに対する非血縁同種骨髄移植の効果

    寺尾 陽子, 山岡 正慶, 横井 健太郎, 秋山 正晴, 小林 博司, 下澤 伸行, 小野寺 理, 加我 牧子, 大橋 十也, 井田 博幸

    日本小児科学会雑誌   117 ( 2 )   410 - 410   2013.2

     More details

    Language:Japanese   Publisher:(公社)日本小児科学会  

    researchmap

  • Aprataxin遺伝子異常ヘテロ接合を認めた早期発症型失調症

    橋本 美沙, 酒井 素子, 久留 聡, 小長谷 正明, 横関 明男, 西澤 正豊, 小野寺 理

    臨床神経学   53 ( 1 )   57 - 57   2013.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • What is the key player in TDP-43 pathology in ALS: Disappearance from the nucleus or inclusion formation in the cytoplasm?

    Osamu Onodera, Akihiro Sugai, Takuya Konno, Mari Tada, Akihide Koyama, Masatoyo Nishizawa

    NEUROLOGY AND CLINICAL NEUROSCIENCE   1 ( 1 )   11 - 17   2013.1

     More details

    Language:English   Publishing type:Book review, literature introduction, etc.   Publisher:WILEY  

    C9ORF72 and the 43 kDa TAR DNA-binding protein (TDP-43) are key molecules in the development of TDP-43 pathology in amyotrophic lateral sclerosis (ALS). The hexanucleotide repeat expansion in C9ORF72 also leads to frontotemporal lobar degeneration, whereas mutation of TARDBP mainly causes ALS, indicating that TDP-43 plays a more fundamental role in the development of ALS. In tissues affected with ALS, TDP-43 is dislocated from the nucleus, forms cytoplasmic inclusions, and is phosphorylated and truncated. Accumulating evidence suggests that the disappearance of TDP-43 from the nucleus precedes inclusion formation, indicating that its disappearance from the nucleus is crucial in the development of TDP-43 pathology. Alterations in the quality and quantity of TDP-43 might result in the disappearance of TDP-43 from the nucleus. Regarding quality, phosphorylation and truncation of TDP-43 is not necessary for its disappearance from the nucleus or for inclusion formation. Although it has been speculated that studies of TDP-43 harboring ALS-associated mutations are useful for understanding the molecular pathogenesis of sporadic ALS, the functional and biochemical differences between mutated and wild-type TDP-43 remain unclear. Regarding quantity, an increased amount of TDP-43 is an attractive hypothesis as it has been shown that increased amounts of TDP-43 are toxic. Moreover, several reports have suggested that increased levels of TDP-43 are found in sporadic ALS as well as in ALS with TDP-43 mutations. However, these findings remain controversial. Increased understanding of the mechanisms responsible for regulating TDP-43 will provide a basis for determining the molecular pathogenesis of ALS.

    DOI: 10.1002/ncn3.9

    Web of Science

    researchmap

  • 神経変性疾患に関する調査研究 本邦におけるC9ORF72変異の創始者効果と紀伊半島における集積について

    石浦浩之, 高橋祐二, 三井純, 市川弥生子, 伊達英俊, 後藤順, 辻省次, 小野寺理, 今野卓哉, 西澤正豊, 吉田宗平, 紀平為子, 小久保康昌, 内藤實, 葛原茂樹, 玉置知子, 富山弘幸, 大垣光太郎, 服部信孝, 和泉唯信, 梶龍兒, 熱田直樹, 祖父江元

    神経変性疾患に関する調査研究 平成24年度 総括・分担研究報告書   22 - 24   2013

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • HDLS患者関連colony stimulating factor-1receptor(CSF-1R)変異体によるCSF-1R介在シグナル伝達障害

    勇亜衣子, 今野卓哉, 他田正義, 小山哲秀, 西澤正豊, 小野寺理, 池内健

    日本分子生物学会年会プログラム・要旨集(Web)   36th   2013

  • 筋萎縮性側索硬化症の分子病態解明と新規治療法創出に関する研究 TDP-43 mRNAの制御機構

    小野寺理, 小山哲秀, 須貝章弘, 今野卓哉, 小山美咲, 石原智彦, 西澤正豊

    筋萎縮性側索硬化症の分子病態解明と新規治療法創出に関する研究 平成22-24年度 総合研究報告書   2013

  • 筋萎縮性側索硬化症の分子病態解明と新規治療法創出に関する研究 TDP-43 mRNAの制御機構

    小野寺理, 小山哲秀, 須貝章弘, 今野卓哉, 小山美咲, 石原智彦, 西澤正豊

    筋萎縮性側索硬化症の分子病態解明と新規治療法創出に関する研究 平成24年度 総括・分担研究報告書   2013

  • HTRA1遺伝子多型と高血圧症との関連:J-MICC横断研究

    栗山長門, 尾崎悦子, 渡邉功, 岩川綾, 原久美子, 御神本奈保美, 松川泰子, 宮谷史太郎, 松井大輔, 小野寺理, 猪原匡史, 水野敏樹, 中川正法, 渡邊能行

    Journal of Epidemiology   23 ( Supplement 1 )   2013

  • 脳小血管病による大脳白質病変に対するスタチン製剤の影響

    佐藤 達哉, 赤岩 靖久, 若杉 三奈子, 西澤 智恵子, 三瓶 一弘, 川崎 昭一, 百津 健, 小野寺 理, 遠藤 直人, 西澤 正豊

    臨床神経学   52 ( 12 )   1413 - 1413   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ロシア・ヤクート人との比較によるSCA1発症に関わる環境・遺伝学的要因の検討

    他田 正義, 徳永 純, Maksimova N, Varlamova M, 堅田 慎一, 高橋 俊昭, Nikolaeva I, Sukhomyasova A, 土屋 美由紀, 池内 健, 小野寺 理, 西澤 正豊

    臨床神経学   52 ( 12 )   1558 - 1558   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン重合体形成阻害剤のスクリーニングを目的としたモデル線虫の構築

    徳永 純, 他田 正義, 高橋 俊昭, 高橋 有香, 鹿野 智美, 小山 哲秀, 堅田 慎一, 山中 邦俊, 小野寺 理, 西澤 正豊

    臨床神経学   52 ( 12 )   1556 - 1556   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43とFUSはショウジョウバエモデルにおいて相乗的に神経変性を惹き起こす

    藤掛 伸宏, 高橋 光里, 斉藤 勇二, 小野寺 理, 和田 圭司, 永井 義隆

    臨床神経学   52 ( 12 )   1603 - 1603   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS患者神経組織ではスプライシング関連機能性RNAが低下する

    石原 智彦, 志賀 篤, 横尾 麻衣子, 有泉 優子, 横関 明男, 譚 春鳳, 柿田 明美, 西澤 正豊, 高橋 均, 小野寺 理

    臨床神経学   52 ( 12 )   1409 - 1409   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 片側アリルにのみHTRA1ミスセンス変異を有する例でも脳小血管病を引き起こす

    野崎 洋明, 二本松 萌, 斎藤 洋兵, 針生 真弥, 水野 敏樹, 水田 依久子, 志賀 篤, 小山 哲秀, 加藤 泰介, 野田 智子, 垣内 無一, 伊藤 彰一, 西澤 正豊, 小野寺 理

    臨床神経学   52 ( 12 )   1400 - 1400   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 本邦におけるc9FTD/ALSの遺伝・病理学的検討

    今野 卓哉, 志賀 篤, 辻野 彰, 加藤 泰介, 金井 数明, 横関 明男, 江口 博人, 桑原 聡, 西澤 正豊, 高橋 均, 小野寺 理

    臨床神経学   52 ( 12 )   1549 - 1549   2012.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Arrhythmia-associated Variants in the SCN5A Promoter and Regulatory Regions

    Nobue Yagihara, Hiroshi Watanabe, Thomas C. Atack, Seiko Ohno, Wataru Shimizu, Stephanie Chatel, Tamara T. Koopmann, Ping Yang, Marylyn D. Ritchie, Stephen Turner, Kanae Hasegawa, Minako Wakasugi, Osamu Onodera, Ryozo Kuwano, Laetitia Duboscq-Bidot, Richard Redon, Minoru Horie, Jean-Jacques Schott, Makoto Takayama, Yukiko Nakano, Connie R. Bezzina, Arthur A. Wilde, Takeshi Momotsu, Naoto Endo, Dawood Darbar, Dan M. Roden, Naomasa Makita

    CIRCULATION   126 ( 21 )   2012.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Aprataxin遺伝子異常ヘテロ接合による早期発症型失調症

    橋本 美沙, 酒井 素子, 久留 聡, 小長谷 正明, 横関 明男, 西澤 正豊, 小野寺 理

    国立病院総合医学会講演抄録集   66回   566 - 566   2012.11

     More details

    Language:Japanese   Publisher:国立病院総合医学会  

    researchmap

  • 小脳症状とは何か 小脳症状とは何か 治療研究にむけた適切な評価方法を目指して

    小野寺 理

    臨床神経学   52 ( 11 )   988 - 989   2012.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 血管性認知症の最先端 CARASILの分子病態機序

    小野寺 理

    Dementia Japan   26 ( 4 )   425 - 425   2012.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • C9ORF72変異を有する家族性筋萎縮性側索硬化症の神経生理学的検討

    岩井 雄太, 澁谷 和幹, 三澤 園子, 磯瀬 沙希里, 関口 縁, 那須 彩子, 藤巻 由実, 別府 美奈子, 大森 茂樹, 杉本 一男, 金井 数明, 小野寺 理, 桑原 聡

    臨床神経生理学   40 ( 5 )   457 - 457   2012.10

     More details

    Language:Japanese   Publisher:(一社)日本臨床神経生理学会  

    researchmap

  • 若年性認知症を呈する白質脳症 HDLS患者のCSF1R変異、MRI所見、臨床像、病理像の検討

    今野 卓哉, 他田 正義, 小山 哲秀, 荒川 武蔵, 岡崎 健一, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理, 池内 健

    Dementia Japan   26 ( 4 )   472 - 472   2012.10

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    J-GLOBAL

    researchmap

  • 隠れ脳梗塞を考える

    小野寺 理

    新潟県医師会報   ( 749 )   2 - 5   2012.8

     More details

    Language:Japanese   Publisher:新潟県医師会  

    多くの患者が、頭部MRIで見つけられた白質病変に対して「隠れ脳梗塞」との説明を受けている。しかし、「隠れ脳梗塞」は真に脳梗塞であろうか?「隠れ脳梗塞」の大多数は、その病態の首座が脳の小さな血管に由来すると考えられている。疫学研究からも、小血管に由来するこれらの病態は大血管に由来する脳梗塞とは危険因子が異なることが判明している。近年、脳の小血管には、脳梗塞とは別の脳小血管病という概念が提唱されている。脳小血管の解剖、脳小血管病の病理所見、原因の判明している脳小血管病の病態機序について述べた。

    researchmap

  • 【わが国の遺伝性ALS】ALS10(TARDBP遺伝子変異によるALS)

    横関 明男, 石原 智彦, 今野 卓哉, 西澤 正豊, 小野寺 理

    神経内科   76 ( 5 )   489 - 496   2012.5

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【類似する神経症候・徴候を正しく理解する-神経診断のピットフォール】 孤発性脳小血管病と遺伝性脳小血管病

    野崎 洋明, 西澤 正豊, 小野寺 理

    Clinical Neuroscience   30 ( 5 )   553 - 555   2012.5

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • C9ORF72遺伝子の非翻訳領域におけるGGGGCCリピート異常伸長を伴うFTD/ALS

    今野 卓哉, 志賀 篤, 西澤 正豊, 高橋 均, 小野寺 理

    Dementia Japan   26 ( 2 )   206 - 215   2012.4

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    J-GLOBAL

    researchmap

  • 脳小血管病の分子病態機序 CARASILからのアプローチ

    小野寺 理

    老年期認知症研究会誌   19 ( 2 )   38 - 40   2012.2

     More details

    Language:Japanese   Publisher:老年期認知症研究会  

    researchmap

  • 【Small-vessel disease】 脳小血管病と遺伝性脳小血管病

    関根 有美, 野崎 洋明, 西澤 正豊, 小野寺 理

    循環器内科   71 ( 2 )   140 - 144   2012.2

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • Disruption of microtubule-dependent transport triggers cytoplasmic aggregation of TDP-43, leading to neurodegeneration in Drosophila

    Nobuhiro Fujikake, Nobuyuki Kimura, Yuji Saitoh, Akio Yokoseki, Osamu Onodera, Keiji Wada, Yoshitaka Nagai

    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS   33   277 - 278   2012

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • Disruption of microtubule-dependent transport triggers cytoplasmic aggregation of TDP-43, leading to neurodegeneration in Drosophila

    Nobuhiro Fujikake, Nobuyuki Kimura, Yuji Saitoh, Akio Yokoseki, Osamu Onodera, Keiji Wada, Yoshitaka Nagai

    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS   33   32 - 32   2012

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • Primary Lateral Sclerosis: An Immunohistochemical and Biochemical Study of Pathological TDP-43 in Two Cases

    Takayuki Kosaka, Fu Yong-Juan, Atsushi Shiga, Osamu Onodera, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    DEMENTIA AND GERIATRIC COGNITIVE DISORDERS   33   93 - 93   2012

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • Clinical and Genetic Feature of Japanese CADASIL

    Toshiki Mizuno, Ikuko Mizuta, Akiko Hosomi-Watanabe, Ai Hamano, Yumiko Azuma, Masaki Kondo, Osamu Onodera, Masanori Nakagawa

    CEREBROVASCULAR DISEASES   34   45 - 45   2012

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • 神経変性疾患に関する調査研究 RNA代謝異常の観点から TDP-43の自己調節機能の観点からのALSの病態機序の考察

    小野寺理, 横関明男, 有泉優子, 佐藤達哉, 近藤千草, 石原智彦, 桑原美咲, 今野拓也, 加藤泰介, 西澤正豊, 小山哲秀, 志賀篤, 譚春風, 豊島靖子, 高橋均, 廣川祥子, 佐藤俊哉, 横山峰介

    神経変性疾患に関する調査研究 平成23年度 総括・分担研究報告書   2012

  • 神経変性疾患に関する調査研究 C9ORF72遺伝子のGGGGCCリピートの異常伸長を認めたFALS

    小野寺理, 今野卓哉, 志賀篤, 辻野彰, 加藤泰介, 金井数明, 横関明男, 江口博人, 桑原聡, 西澤正豊, 高橋均

    神経変性疾患に関する調査研究 平成23年度 総括・分担研究報告書   2012

  • HDLSの分子病態と白質を主病変とする他疾患との異同

    池内健, 今野卓哉, 他田正義, 荒川武蔵, 岡崎健一, 小山哲秀, 酒井直子, 野崎洋明, 徳永純, 河内泉, 柿田明美, 高橋均, 西澤正豊, 小野寺理

    日本神経学会学術大会プログラム・抄録集   53rd   2012

  • 多系統萎縮症におけるグレリン分泌異常 gut-brain axis障害の可能性

    小澤 鉄太郎, 徳永 純, 荒川 武蔵, 竹内 亮子, 小野寺 理, 西澤 正豊

    臨床神経学   51 ( 12 )   1269 - 1269   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 特定疾患臨床調査個人票を用いた脊髄小脳変性症6型の自然史調査

    安井 建一, 矢部 一郎, 佐々木 秀直, 新井 公人, 金井 数明, 桑原 聡, 吉田 邦広, 伊藤 瑞規, 祖父江 元, 児矢野 繁, 小野寺 理, 西澤 正豊, 中島 健二

    臨床神経学   51 ( 12 )   1270 - 1270   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CARASILのMRI画像

    野崎 洋明, 福武 敏夫, 下江 豊, 平山 幹生, 柳川 宗平, 西本 祥仁, 柴田 護, 鈴木 則宏, 西澤 正豊, 小野寺 理

    臨床神経学   51 ( 12 )   1215 - 1215   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 副腎白質ジストロフィー患者におけるPEX5遺伝子の全塩基配列解析及び表現型における関連解析

    松川 敬志, 高橋 祐二, 後藤 順, 鈴木 康之, 下澤 伸行, 高野 弘基, 小野寺 理, 西澤 正豊, 辻 省次

    臨床神経学   51 ( 12 )   1304 - 1304   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43の選択的スプライシングを介した自己発現調節

    石原 智彦, 桑原 美咲, 志賀 篤, 藤野 赳至, 近藤 千草, 西澤 正豊, 小野寺 理

    臨床神経学   51 ( 12 )   1273 - 1273   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43を発現するALSモデルショウジョウバエにおけるオートファジー系蛋白質分解の関与

    藤掛 伸宏, 斉藤 勇二, 横関 明男, 小野寺 理, 和田 圭司, 永井 義隆

    臨床神経学   51 ( 12 )   1315 - 1315   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 禿頭を欠くCARASILにおいて認められた新規HTRA1遺伝子変異に関する分子生物学的考察

    西本 祥仁, 柴田 護, 二本松 萌, 野崎 洋明, 志賀 篤, 白田 明子, 山根 清美, 小堺 有史, 高橋 一司, 西澤 正豊, 小野寺 理, 鈴木 則宏

    臨床神経学   51 ( 12 )   1309 - 1309   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 佐渡島における大脳白質病変の経時的変化の検討

    赤岩 靖久, 荒川 博之, 三瓶 一弘, 高野 弘基, 小野寺 理, 西澤 正豊

    臨床神経学   51 ( 12 )   1327 - 1327   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ヒト疾患脳におけるポリグルタミン病重合体の検出

    高橋 俊昭, 石平 悠, 堅田 慎一, 他田 正義, 他田 真理, 佐藤 俊哉, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊

    臨床神経学   51 ( 12 )   1272 - 1272   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 重合体形成阻害を標的としたポリグルタミン病の新規治療法開発

    他田 正義, 高橋 俊昭, 小野寺 理, 西澤 正豊, Paulson Henry L

    臨床神経学   51 ( 12 )   1272 - 1272   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43機能喪失によるゴルジ装置の断片化

    有泉 優子, 横尾 麻理子, 石平 悠, 佐藤 達哉, 桑原 美咲, 志賀 篤, 高橋 俊昭, 西澤 正豊, 小野寺 理

    臨床神経学   51 ( 12 )   1272 - 1272   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 本邦におけるCADASILの新しい診断基準の妥当性について

    水野 敏樹, 冨井 康宏, 水田 依久子, 細見 明子, 小野寺 理, 中川 正法

    臨床神経学   51 ( 12 )   1250 - 1250   2011.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【認知症学 下-その解明と治療の最新知見-】 臨床編 血管性認知症とその類縁疾患 CADASIL(皮質下梗塞および白質脳症を伴う常染色体優性脳動脈症)とCARASIL(皮質下梗塞と白質脳症を伴う脳常染色体劣性動脈症)

    加藤 泰介, 西澤 正豊, 小野寺 理

    日本臨床   69 ( 増刊10 認知症学(下) )   320 - 324   2011.12

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • 皮質下性血管障害の病態と治療 TGF-βファミリーシグナルの異常と脳小血管病

    小野寺 理

    臨床神経学   51 ( 11 )   943 - 944   2011.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【ALS-臨床と分子病態研究の進歩】家族性ALS ALS10(遺伝性ALS-TDP)の臨床と病理

    今野 卓哉, 石原 智彦, 西澤 正豊, 小野寺 理

    Clinical Neuroscience   29 ( 9 )   1019 - 1021   2011.9

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • Dysregulation of TGF-β family signaling and hereditary cerebral small vessel disease : insight into molecular pathogenesis of CARASIL

    NOZAKI Hiroaki, NISHIZAWA Masatoyo, ONODERA Osamu

    Nihon Naika Gakkai Kaishi   100 ( 8 )   2207 - 2213   2011.8

     More details

    Language:Japanese   Publisher:The Japanese Society of Internal Medicine  

    DOI: 10.2169/naika.100.2207

    CiNii Article

    CiNii Books

    researchmap

    Other Link: https://jlc.jst.go.jp/DN/JALC/00375701533?from=CiNii

  • 新規HTRA1遺伝子変異を有し禿頭を欠いたCARASILの44歳女性例

    西本 祥仁, 柴田 護, 小堺 有史, 小野寺 理, 鈴木 則宏

    臨床神経学   51 ( 7 )   522 - 522   2011.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脳小血管病とは何か

    小野寺 理

    臨床神経学   51 ( 6 )   399 - 405   2011.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    近年、脳小血管病という言葉が注目を集めている。脳小血管病は、脳梗塞の再発、認知機能の悪化、歩行障害などと関連し、その病態の解明が急務である。脳小血管は、構造、構成する細胞や分子がことなるいくつかの血管を指す。そのうち、毛細血管は周皮細胞という細胞を持ち、血液脳関門、血管壁による老廃物の排出という機構を担う。今まで判明した多くの遺伝性脳小血管病では、平滑筋細胞の脱落、中膜の変性をみとめる。これは、間質液の排出障害や、周皮細胞の障害による毛細血管の機能不全をひきおこす可能性もある。今後、小血管の機能解剖がより詳細に解明されるにつれて、本症が解明されることが期待される。(著者抄録)

    DOI: 10.5692/clinicalneurol.51.399

    researchmap

  • Plasma ghrelin levels are affected in patients with multiple system atrophy: Evidence of gut-brain axis dysfunction

    T. Ozawa, J. Tokunaga, M. Arakawa, R. Takeuchi, O. Onodera, M. Nishizawa

    MOVEMENT DISORDERS   26   S262 - S262   2011.5

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL  

    Web of Science

    researchmap

  • 【血管性認知症のニューホライズン】 遺伝性脳小血管病の病態機序から脳小血管病を探る

    小野寺 理

    Dementia Japan   25 ( 1 )   24 - 31   2011.4

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 各種疾患 変性疾患 CARASILの臨床・病理像と病態機序

    野崎 洋明, 西澤 正豊, 小野寺 理

    Annual Review神経   2011   251 - 259   2011.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalo-pathy(CARASIL)は,若年成人発症の進行性脳症,禿頭,急性腰痛あるいは変形性脊椎症を呈する常染色体劣性遺伝性の脳小血管病であり,本邦において,臨床,病理,分子病態が確立されてきた疾患である.孤発性の脳小血管病であるBinswanger病とも共通の病理所見を認めることから,孤発性脳小血管病の病態機序との関連が注目されている.本稿では,本症の臨床・病理像および病態機序について述べる.(著者抄録)

    researchmap

  • ALS関連蛋白TDP-43の自己発現調節機能に関与するスプライシング因子の検討

    桑原美咲, 石原智彦, 志賀篤, 今野卓哉, 小山哲秀, 西澤正豊, 小野寺理

    日本分子生物学会年会プログラム・要旨集(Web)   34th   2011

  • ヒト脳組織中のポリグルタミン蛋白質オリゴマーの検出 ポリグルタミン病の分子病態(Detection of oligomers of polyglutamine protein in human brain tissues: implication for molecular parthenogenesis of polyglutamine diseases)

    石平 悠, 高橋 俊昭, 堅田 慎一, 佐藤 俊哉, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   2P - 0926   2010.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • Clinical manual of Charcot-Marie-Tooth disease

    NAKAGAWA Masanori, SHIGA Kensuke, HAYASAKA Kiyoshi, HACHISUKA Kenji, YAMASHITA Toshihiko, TAKASHIMA Hiroshi, HATTORI Naoki, ONODERA Osamu, OHTAKE Hiroaki, YAMADA Takashi

    21 ( 2 )   366 - 367   2010.12

     More details

  • CARASILの病態機序にTGF-βファミリーシグナルの亢進が関与する

    野崎 洋明, 志賀 篤, 横関 明男, 河田 浩敏, 有馬 邦正, 原 賢寿, 福武 敏夫, 柳川 宗平, 田中 亨, 中野 今治, 池田 修一, 山本 格, 池内 健, 西澤 正豊, 辻 省次, 小野寺 理

    臨床神経学   50 ( 12 )   1090 - 1090   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43を発現する新規ALSモデルショウジョウバエを用いた病態解析

    永井 義隆, 藤掛 伸宏, 齊藤 勇二, 横関 明男, 小野寺 理, 和田 圭司

    臨床神経学   50 ( 12 )   1085 - 1085   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43のリン酸化による細胞内局在、凝集体形成の検討

    有泉 優子, 横尾 麻理子, 志賀 篤, 石原 智彦, 横関 明男, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1199 - 1199   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • βアミロイド依存性タウリン酸化カスケードにおけるインスリンシグナル障害の関与

    徳武 孝允, 池内 健, 春日 健作, 篠崎 真, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1106 - 1106   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CARASILの原因遺伝子HTRA1の同定と機能解析

    原 賢寿, 志賀 篤, 福武 敏夫, 宮下 哲典, 横関 明男, 高橋 俊昭, 田村 正人, 下江 豊, 平山 幹夫, 有里 敬代, 柳川 宗平, 中野 今治, 池田 修一, 吉田 豊, 池内 健, 桑野 良三, 西澤 正豊, 辻 省次, 小野寺 理

    臨床神経学   50 ( 12 )   1075 - 1075   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PML発現賦活によるポリグルタミン病の治療検討

    高橋 俊昭, 日高 梓, 堅田 慎一, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1083 - 1083   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 筋萎縮性側索硬化症におけるsnRNAの変化(Alteration of snRNAs in amyotrophic lateral sclerosis)

    石原 智彦, 志賀 篤, 柿田 明美, 横関 明男, 西澤 正豊, 高橋 均, 小野寺 理

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   2P - 0917   2010.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • TDP-43の喪失により、細胞内膜系関連遺伝子のスプライシング異常が起こる(TDP-43 depletion causes aberrant splicing in the genes associated with endomembrane system)

    志賀 篤, 石原 智彦, 宮下 哲典, 横尾 麻理子, 有泉 優子, 横関 明男, 桑野 良三, 西澤 正豊, 小野寺 理

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   2P - 0916   2010.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • TGF-β経路は遺伝性脳小血管病で特異的に活性化される(TGF-β pathway is specifically activated in hereditary cerebral small-vessel disease)

    二本松 萌, 志賀 篤, 野崎 洋明, 西澤 正豊, 小野寺 理

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   4P - 1121   2010.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • 多系統萎縮症とパーキンソン病に共通して見られる腸音発生頻度の低下

    小澤 鉄太郎, 佐治 越爾, 矢島 隆二, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1261 - 1261   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 低アルブミン血症と眼球運動失行を伴う早発型失調症39家系の臨床遺伝学的検討

    横関 明男, 石原 智彦, 山田 光則, 伊達 英俊, 辻 省次, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1081 - 1081   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • TDP-43と核内小体の構成蛋白との蛋白間相互作用の検討

    佐藤 達哉, 横尾 麻理子, 有泉 優子, 石原 智彦, 小野寺 理, 西澤 正豊

    臨床神経学   50 ( 12 )   1199 - 1199   2010.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Notchシグナル 疾患メカニズムの理解に向けて 遺伝性脳小血管病の新しい分子メカニズム(Notch signaling: toward understanding disease mechanisms Novel molecular mechanism for hereditary cerebral small-vessel diseases)

    小野寺 理

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   83回・33回   3W11 - 4   2010.12

     More details

    Language:English   Publisher:(公社)日本生化学会  

    researchmap

  • 【認知症 研究・臨床の最先端】 臨床トピックス 遺伝性脳小血管病

    今野 卓哉, 小野寺 理

    医学のあゆみ   235 ( 6 )   745 - 748   2010.11

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    皮質下白質病変を主体とする脳小血管病に関連した認知症が注目されている。近年、遺伝性の脳小血管病の原因遺伝子がつぎつぎと同定されており、病態との関連が明らかにされつつある。遺伝性脳小血管病の分子病態機序が明らかにされれば、孤発性脳小血管病の病態機序の理解にもつながり、また治療法の開発に寄与することも期待できる。本稿ではCADASIL、CARASIL、脳アミロイドアンギオパチー、Fabry病、RVCL、COL4A1変異についてその臨床像を紹介し、遺伝子異常から推察される病態機序について、これまでの知見を概説する。(著者抄録)

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00060&link_issn=&doc_id=20101105020021&doc_link_id=issn%3D0039-2359%26volume%3D235%26issue%3D6%26spage%3D745&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D235%26issue%3D6%26spage%3D745&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • Machado-Joseph病におけるオヌフ核の障害

    山田 光則, 清水 宏, 豊島 靖子, 池内 健, 小野寺 理, 高橋 均

    国立病院総合医学会講演抄録集   64回   576 - 576   2010.11

     More details

    Language:Japanese   Publisher:国立病院総合医学会  

    researchmap

  • 認知症研究の新しい視点 TDP-43プロテイノパチーとしてのFTLD/ALS

    石原 智彦, 有泉 優子, 志賀 篤, 横関 明男, 佐藤 達哉, 豊島 靖子, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   50 ( 11 )   1022 - 1024   2010.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    DOI: 10.5692/clinicalneurol.50.1022

    researchmap

  • 筋萎縮性側索硬化症の病因TDP-43およびFUS/TLS研究の最前線 TDP-43/ALSの臨床と病理

    小野寺 理, 横関 明男, 譚 春鳳, 石原 智彦, 西平 靖, 豊島 靖子, 柿田 明美, 西澤 正豊, 高橋 均

    臨床神経学   50 ( 11 )   940 - 942   2010.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    DOI: 10.5692/clinicalneurol.50.940

    researchmap

  • Pathogenesis of ALS: in terms of FUS

    235 ( 3 )   236 - 240   2010.10

  • 【ALS Update】 ALSの病態 FUSの観点から

    志賀 篤, 西澤 正豊, 小野寺 理

    医学のあゆみ   235 ( 3 )   236 - 240   2010.10

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    筋萎縮性側索硬化症(ALS)は呼吸不全から死に至る難病である。しかし、その病態機序の多くは不明であり、有効な治療法も開発されていない。近年、DNA/RNA結合蛋白であるTAR DNA binding protein-43(TDP-43)やfused in sarcoma(FUS)が家族性ALSの原因遺伝子として同定され、これらの分子間の機能的・構造的類似性からRNA代謝の異常と運動神経細胞死との関連が注目されている。本稿ではFUSの機能や、その異常とALS病態との関連について概説する。(著者抄録)

    researchmap

  • 遺伝子診断は誰のためか

    小野寺 理

    日本遺伝カウンセリング学会誌   31 ( 2 )   87 - 91   2010.9

     More details

    Language:Japanese   Publisher:日本遺伝カウンセリング学会  

    researchmap

  • 本邦におけるCADASILの新しい診断基準について

    水野 敏樹, 小野寺 理, 冨本 秀和, 内野 誠, 中島 健二, 細見 明子, 西郷 和洋, 笹山 博司, 水田 依久子, 中川 正法

    Dementia Japan   24 ( 3 )   333 - 333   2010.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 血管性認知症のニューホライズン 遺伝性血管性認知症

    小野寺 理

    Dementia Japan   24 ( 3 )   243 - 243   2010.9

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions in sporadic amyotrophic lateral sclerosis

    Y. Nishihira, C. F. Tan, Y. Toyoshima, M. Yamada, H. Takahashi, O. Onodera, T. Morita, M. Nishizawa, A. Kakita

    BRAIN PATHOLOGY   20   32 - 32   2010.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    Web of Science

    researchmap

  • Disequilibrium in MSA phenotype distribution between populations: genetics or environment?

    T. Ozawa, J. L. Holton, D. Paviour, A. J. Lees, M. Tada, A. Kakita, O. Onodera, K. Wakabayashi, H. Takahashi, M. Nishizawa, T. Revesz

    BRAIN PATHOLOGY   20   29 - 29   2010.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL PUBLISHING, INC  

    Web of Science

    researchmap

  • TDP-43を発現する新規ALSモデルショウジョウバエの樹立とその病態解析(Establishment of novel Drosophila models of ALS expressing TDP-43, and analyses of its pathomechanisms)

    藤掛 伸宏, 斉藤 勇二, 横関 明男, 小野寺 理, 和田 圭司, 永井 義隆

    神経化学   49 ( 2-3 )   670 - 670   2010.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • 【神経変性疾患におけるTDP-43】家族性筋萎縮性側索硬化症とTDP-43

    石原 智彦, 横関 明男, 西澤 正豊, 高橋 均, 小野寺 理

    最新医学   65 ( 7 )   1648 - 1653   2010.7

     More details

    Language:Japanese   Publisher:(株)最新医学社  

    筋萎縮性側索硬化症(ALS)の病態機序において,TDP-43の異常が一義的な役割を果たすとされ注目されている.TDP-43遺伝子変異を有するALSはALS-10と分類され,その臨床・病理像は孤発性ALSと全く同じである.近年見いだされた遺伝性に運動神経細胞死を引き起こす遺伝子群は,TDP-43をはじめとしてRNA代謝に関与するという共通の機能を持つ.今後のALS研究では,これらの遺伝子異常によるRNA代謝障害が重要な意義を持つ.(著者抄録)

    researchmap

  • CARASILの分子病態学

    志賀 篤, 野崎 洋明, 西澤 正豊, 小野寺 理

    BRAIN and NERVE: 神経研究の進歩   62 ( 6 )   595 - 599   2010.6

     More details

    Language:Japanese   Publisher:(株)医学書院  

    遺伝性の脳小血管病であるCARASIL(皮質下梗塞と白質脳症を伴う常染色体劣性遺伝性脳動脈硬化症)の病態機序解明は孤発性の脳小血管病の理解に繋がると思われる。CARASILの原因遺伝子であるHTRA1の機能異常とその分子病態機序との関連について、以下の項目別に概説した。1)HTRA1の同定、2)HTRA1の構造と機能、3)CARASILはHTRA1の機能喪失により引き起こされる、4)HTRA1遺伝子変異によってTGF-βファミリーシグナルが亢進する、5)CARASILの病態とTGF-βファミリーシグナルの異常との関連。

    researchmap

  • 脳神経の分子イメージング 封入体形成前のポリグルタミンオリゴマーは細胞毒性を発揮する

    高橋 俊昭, 堅田 慎一, 小野寺 理, 西澤 正豊

    JSMI Report   3 ( 2 )   30 - 30   2010.5

     More details

    Language:Japanese   Publisher:日本分子イメージング学会  

    researchmap

  • CARASILの分子病態から脳小血管病を探る

    小野寺 理

    臨床神経学   50 ( 5 )   336 - 336   2010.5

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【遺伝性脳血管病(CADASILとCARASIL)】 CARASILの分子病態機序

    野崎 洋明, 志賀 篤, 西澤 正豊, 小野寺 理

    神経内科   72 ( 4 )   408 - 412   2010.4

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 遺伝子診断は誰のためか

    小野寺 理

    日本遺伝カウンセリング学会誌   31 ( 1 )   38 - 38   2010.4

     More details

    Language:Japanese   Publisher:日本遺伝カウンセリング学会  

    researchmap

  • Cytoplasmic C-Terminus TDP-43 Aggregate Leads to Increased Phosphorylation of Full-Length TDP-43 in Culture Cell

    Yuko Ariizumi, Tomohiko Ishihara, Mariko Yokoo, Atsushi Shiga, Akio Yokoseki, Osamu Onodera, Masatoyo Nishizawa

    NEUROLOGY   74 ( 9 )   A502 - A502   2010.3

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • 【Spinocerebellar ataxia(SCA)】 Spinocerebellar ataxia type 15

    原 賢寿, 小野寺 理

    神経内科   72 ( 2 )   185 - 189   2010.2

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • Establishment of novel Drosophila models of ALS expressing TDP-43, and analyses of its pathomechanisms

    Nobuhiro Fujikake, Yuji Saitoh, Akio Yokoseki, Osamu Onodera, Keiji Wada, Yoshitaka Nagai

    NEUROSCIENCE RESEARCH   68   E308 - E308   2010

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.1368

    Web of Science

    researchmap

  • 【癌治療・発癌・老化の鍵を握るDNA修復経路】 DNA一本鎖切断損傷修復の破綻による神経変性疾患

    他田 正義, 辻 省次, 西澤 正豊, 小野寺 理

    細胞工学   29 ( 1 )   60 - 66   2009.12

     More details

    Language:Japanese   Publisher:(株)学研メディカル秀潤社  

    researchmap

  • ALS関連変異型TDP43の細胞内動態の検討

    有泉 優子, 志賀 篤, 石原 智彦, 横尾 麻理子, 横関 明男, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   1027 - 1027   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 遺伝子変異を伴った家族性アルツハイマー病の表現型の比較

    池内 健, 春日 健作, 野崎 洋明, 石原 智彦, 金子 博之, 篠崎 真, 桑野 良三, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   984 - 984   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脊髄小脳失調症6型の多施設共同自然史調査

    安井 建一, 矢部 一郎, 佐々木 秀直, 吉田 邦広, 金井 数明, 服部 孝道, 新井 公人, 伊藤 瑞規, 祖父江 元, 児矢野 繁, 小野寺 理, 西澤 正豊, 中島 健二

    臨床神経学   49 ( 12 )   1114 - 1114   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALS関連変異型TDP-43の機能と細胞毒性の検討

    横関 明男, 志賀 篤, 小池 佑佳, 石原 智彦, 有泉 優子, 横尾 麻理子, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   1055 - 1055   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 疾患関連変異型APTXの蛋白不安定化機序の解明

    佐藤 達哉, 小山 哲秀, 横関 明男, 他田 正義, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   982 - 982   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 伸長ポリグルタミン鎖は二量体で細胞毒性を示す

    堅田 慎一, 高橋 俊昭, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   1118 - 1118   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン蛋白の立体構造と重合様式の検討

    高橋 俊昭, 堅田 慎一, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   1117 - 1117   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 認知症性疾患の髄液バイオマーカーとしてのαシヌクレインの検討

    春日 健作, 池内 健, 石川 厚, 徳田 隆彦, 中川 正法, 小野寺 理, 西澤 正豊

    臨床神経学   49 ( 12 )   1141 - 1141   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 日本人MSA剖検例の表現型スペクトラム 英国の結果と対比して

    小澤 鉄太郎, 他田 真理, 小野寺 理, 柿田 明美, 高橋 均, 西澤 正豊

    臨床神経学   49 ( 12 )   1133 - 1133   2009.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脊髄小脳変性症の分子病態機序の解明

    小野寺 理

    臨床神経学   49 ( 11 )   750 - 752   2009.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    神経細胞の機能を維持するために、神経細胞の内部環境を維持する品質管理機構が重要である。とくに蛋白質と核酸の品質管理機構と神経変性疾患との関係が注目されている。代表的な優性遺伝性脊髄小脳変性症であるポリグルタミン病では、蛋白質の品質管理機構の異常が推察されている。一方、劣性遺伝性脊髄小脳変性症では核酸品質管理機構の異常が推察されている。神経細胞のDNAは活性酸素などにより常に障害をうけ損傷している。損傷部の3&#039;末断端はリン酸基、ホスホグリコール酸基または不飽和アルデヒド基となっており、修復のためには、水酸基に置換(エンド・プロセッシング)される必要がある。われわれは劣性遺伝性脊髄小脳失調症の原因遺伝子アプラタキシンの生理機能を検討し、この蛋白質がin vitroにおいて3&#039;末断端のリン酸基およびホスホグリコール酸基を除去し水酸基とする活性を持ち、これにより損傷部のエンド・プロセッシングに関与していることを示した。このことから、本症の病態機序としてDNA損傷の蓄積の関与を示唆し、脊髄小脳変性症での核酸品質管理機構の重要性を示した。(著者抄録)

    DOI: 10.5692/clinicalneurol.49.1

    researchmap

  • 【前頭側頭葉変性症】TDP-43の遺伝子変異とその意義

    石原 智彦, 横関 明男, 西澤 正豊, 高橋 均, 小野寺 理

    BRAIN and NERVE: 神経研究の進歩   61 ( 11 )   1301 - 1307   2009.11

     More details

    Language:Japanese   Publisher:(株)医学書院  

    researchmap

  • 【最新・脳血管疾患Update 研究と臨床の最前線】 脳血管疾患の診断の最前線 遺伝性脳小血管病CARASILおよびCADASIL

    野崎 洋明, 志賀 篤, 小野寺 理

    医学のあゆみ   231 ( 5 )   458 - 461   2009.10

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    脳小血管病は高血圧症を危険因子とするが、その分子病態は不明であった。近年、遺伝性脳小血管病であるCerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL)、およびCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)の原因遺伝子が同定され、その分子病態の解明が進んでいる。CARASILではHtrA1遺伝子変異によるTGF-βシグナルの調節障害が、CADASILではNotch3遺伝子変異によるあらたな蛋白間相互作用が病態に関与することが推定されている。本稿ではこれらの知見を踏まえ、CARASILおよびCADASILの病態機序と診断について概説する。(著者抄録)

    researchmap

  • Aβはインスリンシグナルを障害することでタウの過剰リン酸化を引き起こすか?

    春日 健作, 徳武 孝允, 篠崎 眞, 西澤 正豊, 小野寺 理, 池内 健

    Dementia Japan   23 ( 2 )   202 - 202   2009.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • レビー小体病の大脳皮質におけるαシヌクレイン蓄積とSNCA mRNA発現量の検討

    野崎 洋明, 石平 悠, 金子 博之, 豊島 靖子, 柿田 明美, 高橋 均, 小野寺 理, 西澤 正豊, 池内 健

    Dementia Japan   23 ( 2 )   181 - 181   2009.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【Multifocal fibrosclerosisと神経系】 肥厚性硬膜炎を伴うmultifocal fibrosclerosis

    他田 正義, 小野寺 理, 赤岩 靖久, 河内 泉, 西澤 正豊

    神経内科   71 ( 2 )   170 - 175   2009.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 健忘を主体とする特異な臨床型を呈するタウ遺伝子(MAPT)R406W変異を伴う家族性認知症の臨床分子遺伝学的解析

    池内 健, 春日 健作, 宮下 哲典, 川瀬 康裕, 小野寺 理, 杉下 守弘, 桑野 良三, 西澤 正豊

    Dementia Japan   23 ( 2 )   175 - 175   2009.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 新しい小脳性運動失調の重症度評価スケールScale for the Assessment and Rating of Ataxia(SARA)日本語版の信頼性に関する検討

    佐藤 和則, 矢部 一郎, 相馬 広幸, 安井 建一, 伊藤 瑞規, 下畑 享良, 小野寺 理, 中島 健二, 祖父江 元, 西澤 正豊, 佐々木 秀直

    BRAIN and NERVE: 神経研究の進歩   61 ( 5 )   591 - 595   2009.5

     More details

    Language:Japanese   Publisher:(株)医学書院  

    脊髄小脳変性症66名(女34名、男32名、17〜84歳)を対象に、日本語版のScale for the Assessment and Rating of Ataxia(SARA)を使用し、信頼性について検討した。SARAは全8項目(歩行、立位、坐位、言語障害、指追い試験、鼻指試験、手の回内回外運動、踵すね試験)と評価項目が少なく施行時間が4分と短く簡便で、評価者間の評価のばらつきが少なく他の試験と有意な相関を示してる。日本語版SARAは高い信頼性があることを示すものではあったが、項目別にみると8項目のうち、評価者間比較において指追い試験、手の回内回外運動の2項目において級内相関係数(ICC)が0.8に達しなかった。日本語版SARAは高い信頼性と内的整合性が認められ、日常診療での小脳性運動失調の重症度、経時的変化の評価など簡便性の点からも有用と思われた。

    researchmap

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J04871&link_issn=&doc_id=20090521220011&doc_link_id=40016669037&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40016669037&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 発育鶏胚を用いた新たなポリグルタミン病モデルの構築

    中山 瞳, 柴田 昌宏, 井上 良介, 高橋 俊昭, 小野寺 理, 佐藤 昇

    解剖学雑誌   84 ( Suppl. )   252 - 252   2009.3

     More details

    Language:Japanese   Publisher:(一社)日本解剖学会  

    researchmap

  • 【脳・神経系の画像診断】 疾患各論 白質ジストロフィー

    小野寺 理

    小児科診療   72 ( 3 )   509 - 514   2009.3

     More details

    Language:Japanese   Publisher:(株)診断と治療社  

    researchmap

  • 脊髄小脳変性症の分子病態機序の解明

    小野寺 理

    臨床神経学   49 ( 1 )   1 - 8   2009.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    要旨:神経細胞の機能を維持するために、神経細胞の内部環境を維持する品質管理機構の重要性が明らかとなってきている。とくに蛋白質と核酸の品質管理機構と神経変性疾患との関係が注目されている。優性遺伝性脊髄小脳変性症の代表的な疾患であるポリグルタミン病では、蛋白質の品質管理機構の異常が推察されている。本症では、増大したポリグルタミン鎖が原因となるが、増大ポリグルタミン鎖の細胞傷害性を持つ構造体は明らかではなかった。われわれは、近接した蛍光物質間でおこる蛍光共鳴エネルギー移動現象を利用し、増大ポリグルタミン鎖のオリゴマー状態を可視化する方法を開発した。本法により、増大ポリグルタミン鎖が、平行βシート構造、もしくは順方向性のシリンダー構造のオリゴマーを形成することを示した。また、オリゴマーが、もっとも細胞傷害性が高い構造体であることを示した。一方、劣性遺伝性脊髄小脳変性症の病態機序として、核酸品質管理機構の破綻が注目を集めている。神経細胞のDNAは活性酸素や化学物質により常に障害をうけDNA損傷が生じている。損傷部の3&#039;末断端はリン酸基、ホスホグリコール酸基または不飽和アルデヒド基となっており、修復のためには水酸基にエンド・プロセッシングされる必要がある。われわれは劣性遺伝性脊髄小脳失調症の原因遺伝子アプラタキシンの生理機能を検討し、この蛋白質が、in vitroにおいて、3&#039;末断端のリン酸基およびホスホグリコール酸基を除去し水酸基とする活性を持ち、これにより損傷部のエンド・プロセッシングに関与していることを示した。このことから、本症の病態機序としてDNA損傷の蓄積があることを示し、脊髄小脳変性症での核酸品質管理機構の重要性を明らかにした。(著者抄録)

    DOI: 10.5692/clinicalneurol.49.1

    researchmap

  • 【脊髄小脳変性症 What's new?】 劣性遺伝性家族性 眼球運動失行と低アルブミン血症を伴う早期発症型脊髄小脳失調症(EAOH/AOA1)

    佐藤 達哉, 他田 正義, 小野寺 理

    Clinical Neuroscience   27 ( 1 )   82 - 83   2009.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 末梢神経疾患 眼球運動失行と低アルブミン血症を伴う早期発症型脊髄小脳失調症

    佐藤 達哉, 他田 正義, 小野寺 理

    Annual Review神経   2009   226 - 232   2009.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    眼球運動失行と低アルブミン血症を伴う早期発症型脊髄小脳失調症 early-onset ataxia with ocu-lar motor apraxia and hypoalbuminemia / atax-ia-oculomotor apraxia 1(EAOH / AOA1)は,幼少期発症の緩徐進行性の小脳失調を中核症状とし,病初期に眼球運動失行,進行期に低アルブミン血症および高度の末梢神経障害を呈する,常染色体劣性遺伝性の脊髄小脳失調症である.本症は,APTX遺伝子がコードするaprataxin(APTX)蛋白の機能喪失により発症する.apra-taxinは核および核小体に局在し,DNA単鎖切断損傷修復においてDNAの末端プロセッシングに関与していると考えられている.(著者抄録)

    researchmap

  • The spectrum of pathological involvement in Japanese patients with multiple system atrophy: A population-bound phenotype distribution

    T. Ozawa, M. Tada, O. Onodera, A. Kakita, T. Shimohata, H. Takahashi, N. Nishizawa

    MOVEMENT DISORDERS   24   S416 - S417   2009

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 家族性および早発型アルツハイマー病におけるAPP遺伝子重複 2家系の臨床遺伝学的検討

    春日 健作, 池内 健, 志賀 篤, 徳永 純, 下畑 享良, 桑野 良三, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1243 - 1243   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • オリゴマーの簡易検出法の確立

    堅田 慎一, 高橋 俊昭, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1087 - 1087   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PML小体によるポリグルタミン病治療戦略

    高橋 俊昭, 日高 梓, 堅田 慎一, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1086 - 1086   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脊髄小脳失調症15型の原因遺伝子の同定

    野崎 洋明, 原 賢寿, 志賀 篤, 三井 純, 高橋 祐二, 石黒 英明, 四茂野 はるみ, 栗崎 博司, 後藤 順, 池内 健, 辻 省次, 西澤 正豊, 小野寺 理

    臨床神経学   48 ( 12 )   1239 - 1239   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 日本語版Scale for the Assessment and Rating of Ataxia(SARA)の信頼性

    佐藤 和則, 安井 建一, 中島 健二, 伊藤 瑞規, 祖父江 元, 下畑 享良, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1209 - 1209   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 疾患関連変異型アプラタキシンの核小体局在障害とその機序の解明

    佐藤 達哉, 小山 哲秀, 横関 明男, 他田 正義, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1117 - 1117   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脊髄小脳失調症6型の自然史 多施設共同後ろ向き調査

    安井 建一, 矢部 一郎, 佐々木 秀直, 新井 公人, 金井 数明, 服部 孝道, 吉田 邦広, 磯崎 英治, 小野寺 理, 西澤 正豊, 中島 健二

    臨床神経学   48 ( 12 )   1088 - 1088   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Bunina小体を認める家族性ALSに認めたTDP43ミスセンス変異

    横関 明男, 志賀 篤, 金子 博之, 田川 朝子, 譚 春鳳, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   48 ( 12 )   1122 - 1122   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Aprataxinは神経細胞においてDNA単鎖切断損傷修復に関与する

    他田 正義, 佐藤 達哉, 横関 明男, 小山 哲秀, 志賀 篤, 高橋 哲哉, 小宅 睦郎, 五十嵐 修一, 佐藤 俊哉, 辻 省次, 西澤 正豊, 小野寺 理

    臨床神経学   48 ( 12 )   1120 - 1120   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【前頭側頭葉変性症(FTLD)とALSにおけるTDP-43をめぐる最近の進歩】 Bunina小体のみられる家族性ALSに認めたTDP-43ミスセンス変異

    小野寺 理, 横関 明男, 譚 春鳳, 志賀 篤, 金子 博之, 田川 朝子, 岡本 幸市, 西澤 正豊, 高橋 均

    Dementia Japan   22 ( 3 )   245 - 251   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • プレセニリン1変異による難溶性αシヌクレイン蓄積の分子機序

    池内 健, 金子 博之, 柿田 明美, 春日 健作, 野崎 洋明, 石川 厚, 高橋 均, 小野寺 理, 西澤 正豊

    臨床神経学   48 ( 12 )   1244 - 1244   2008.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 疾患関連変異型アプラタキシンの核小体局在障害とその機序の解明

    佐藤 達哉, 小山 哲秀, 横関 明男, 他田 正義, 小野寺 理, 西澤 正豊

    新潟医学会雑誌   122 ( 12 )   690 - 690   2008.12

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 前頭側頭葉変性症(FTLD)とALSにおけるTDP-43をめぐる最近の進歩 Bunina小体を認める家族性ALSに認めたTDP-43ミスセンス変異

    小野寺 理, 横関 明男, 譚 春鳳, 志賀 篤, 田川 朝子, 岡本 幸市, 西澤 正豊, 高橋 均

    Dementia Japan   22 ( 2 )   91 - 91   2008.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【TDP-43と神経変性疾患】 家族性ALSとTDP-43

    譚 春鳳, 横関 明男, 小野寺 理, 西澤 正豊, 高橋 均

    神経内科   68 ( 6 )   558 - 564   2008.6

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • TAR DNA binding protein-43遺伝子変異を伴った筋萎縮性側索硬化症

    横関 明男, 譚 春鳳, 田川 朝子, 岡本 幸市, 西澤 正豊, 高橋 均, 小野寺 理

    Dementia Japan   22 ( 1 )   60 - 67   2008.4

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 運動失調症に関する調査研究 病態の進行抑制治療に関する臨床研究および基礎研究 I.Scale for the Assessment and Rating of Ataxia(SARA)の有用性,II.ポリグルタミン病における筋エネルギー代謝測定の試み III.MSA疾患感受性候補遺伝子の関連解析

    佐々木秀直, 佐藤和則, 相馬広幸, 矢部一郎, 寺江聡, 沖田孝一, 安井建一, 中島健二, 伊藤瑞規, 祖父江元, 下畑享良, 小野寺理, 西澤正豊

    運動失調症に関する調査研究 平成17−19年度総合 総括・分担研究報告書   20-22   2008

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 運動失調症に関する調査研究 臨床調査個人票等に基づく脊髄小脳変性症SCD,多系統萎縮症MSAの自然歴研究 多系統萎縮症の睡眠呼吸障害と突然死に関する検討および脊髄小脳失調症15型Spinocerebellar Ataxia Type 15(SCA15)の原因遺伝子の同定

    西澤正豊, 小澤鉄太郎, 下畑享良, 志賀篤, 原賢寿, 野崎洋明, 中山秀章, 富田雅彦, 石黒英明, 栗崎博司, 四茂野はるみ, 高橋祐二, 三井純, 後藤順, 辻省次, 池内健, 小野寺理

    運動失調症に関する調査研究 平成17-19年度総合 総括・分担研究報告書   16 - 17   2008

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • 運動失調症に関する調査研究班 脊髄小脳失調症15型Spinocerebellar Ataxia Type 15(SCA15)の原因遺伝子の同定

    西澤正豊, 志賀篤, 原賢寿, 野崎洋明, 石黒英明, 栗崎博司, 四茂野はるみ, 高橋祐二, 三井純, 後藤順, 辻省次, 池内健, 小野寺理

    運動失調症に関する調査研究班 平成19年度 総括・分担研究報告書   71 - 73   2008

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • EAOHの病因蛋白aprataxinは校正機能を有する3'-5'exonucleaseである

    他田 正義, 横関 明男, 高橋 哲哉, 五十嵐 修一, 西澤 正豊, 小野寺 理

    臨床神経学   47 ( 12 )   1157 - 1157   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 増大ポリグルタミン鎖の発現によるPML小体の変化

    堅田 慎一, 高橋 俊昭, 小野寺 理, 西澤 正豊

    臨床神経学   47 ( 12 )   1091 - 1091   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 細胞障害性を示すポリグルタミン鎖構造の同定

    高橋 俊昭, 菊池 信矢, 小野寺 理, 西澤 正豊

    臨床神経学   47 ( 12 )   1130 - 1130   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 認知症を伴う遺伝性パーキンソニズムにおけるα-synuclein遺伝子(SNCA)重複

    池内 健, 春日 健作, 志賀 篤, 金子 博之, 柿田 明美, 内山 剛, 大橋 寿彦, 石川 厚, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   47 ( 12 )   1125 - 1125   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • EAOH/AOA1における遺伝子変異と臨床症状の検討

    横関 明男, 岩淵 潔, 丸田 恭子, 西澤 正豊, 小野寺 理

    臨床神経学   47 ( 12 )   1156 - 1156   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • AOA1/EAOHの病態機序における核小体局在の意義

    小野寺 理, 小山 哲秀, 横関 明男, 他田 正義, 間 由希, 五十嵐 修一, 西澤 正豊

    臨床神経学   47 ( 12 )   1131 - 1131   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 電位依存性P/Q型カルシウムチャネル機能異常と神経疾患

    小野寺 理

    日本頭痛学会誌   34 ( 2 )   146 - 148   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本頭痛学会  

    researchmap

  • 歯状核赤核淡蒼球ルイ体萎縮症(DRPLA)の臨床経過に及ぼす要因についての検討

    長谷川 有香, 福島 隆男, 松原 奈絵, 小池 亮子, 池内 健, 小野寺 理, 西澤 正豊

    臨床神経学   47 ( 12 )   1030 - 1030   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • γセクレターゼによるインスリン受容体の膜内切断および細胞内局在の検討

    春日 健作, 池内 健, 金子 博之, 小山 哲秀, 他田 正義, 西澤 正豊, 小野寺 理

    臨床神経学   47 ( 12 )   1011 - 1011   2007.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Deletion involving the whole type 1 inositol 1,4,5-triphosphate receptor (ITPR1) gene is associated with spinocerebellar ataxia type 15

    Kenju Hara, Atsushi Shiga, Hiroaki Nozaki, Shoji Tsuji, Masatoyo Nishizawa, Osamu Onodera

    ANNALS OF NEUROLOGY   62 ( 5 )   544 - 544   2007.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 【脳神経疾患の分子病態と治療への展開 アルツハイマー病、パーキンソン病、発達障害、精神疾患などの発症メカニズムを分子から解く】 神経難病の病態トピックス DNA修復の異常と劣性遺伝性失調症

    他田 正義, 横関 明男, 小野寺 理

    実験医学   25 ( 13 )   1988 - 1994   2007.8

     More details

    Language:Japanese   Publisher:(株)羊土社  

    近年、劣性遺伝性脊髄小脳変性症(AR-SCD)の原因遺伝子が相次いで同定され、その分子病態が明らかにされつつある。これら疾患の多くは、原因遺伝子の遺伝子産物がDNA修復や複製など核酸品質管理に関与している。特に、DNA単鎖切断損傷に対する修復の異常は、神経系に限局した障害をきたし、小脳および脊髄後索に顕著な神経変性を生じる。DNA損傷に対する修復異常が選択的な神経細胞死をきたす病態機序については不明の点が多く残されているが、これら疾患の根底にある分子病態を明らかにすることにより、複数の疾患に対して応用可能となるような治療法を開発できる可能性があり、注目される。本稿では、DNA修復の異常が発症に関連するAR-SCDのなかで、特にDNA単鎖切断損傷修復の異常が病態に関連する疾患に焦点を当て、その分子病態を中心に解説する。(著者抄録)

    researchmap

  • ロシアのヤクーツク地方に多発する劣性遺伝性小人症のゲノムワイド連鎖解析と原因遺伝子同定

    原 賢寿, Maximova Nadya R, 宮下 哲典, 桑野 良三, 西澤 正豊, 小野寺 理

    新潟医学会雑誌   121 ( 6 )   362 - 362   2007.6

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2008037601

  • 【神経筋疾患の最新研究治療情報】 副腎白質ジストロフィー症の治療

    小野寺 理

    難病と在宅ケア   13 ( 3 )   27 - 30   2007.6

     More details

    Language:Japanese   Publisher:(株)日本プランニングセンター  

    researchmap

  • Multiple system atrophy: Morphometric evaluation of the CNS autonomic nuclei in patients with sudden deaths

    Mari Tada, Akiyoshi Kakita, Osamu Onodera, Masatoyo Nishizawa, Hitoshi Takahashi

    NEUROLOGY   68 ( 12 )   A50 - A50   2007.3

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Aprataxin, the causative gene product for AOA1/EAOH, repairs damaged 3'-ends of DNA single strand breaks

    Masayoshi Tada, Akihide Koyama, Shuichi Igarashi, Akio Yokoseki, Tetsuya Takahashi, Atsushi Shiga, Shoji Tsuji, Masatoyo Nishizawa, Osamu Onodera

    NEUROLOGY   68 ( 12 )   A79 - A79   2007.3

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Aprataxin(APTX)のDNA損傷ストレスにおける核内局在の変化に関する検討

    五十嵐 修一, 小山 哲秀, 他田 正義, 高橋 哲哉, 高橋 俊昭, 小野寺 理, 西澤 正豊

    臨床神経学   46 ( 12 )   1148 - 1148   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Actin結合蛋白L-plastinはポリグルタミン病で増加する

    長谷川 有香, 高橋 俊昭, 豊島 靖子, 吉田 豊, 高橋 均, 西澤 正豊, 小野寺 理

    臨床神経学   46 ( 12 )   1020 - 1020   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Puratrophin-1遺伝子5'UTRのC→T置換を伴う脊髄小脳変性症の臨床遺伝学的検討

    野崎 洋明, 池内 健, 川上 明男, 新保 淳輔, 原 賢寿, 豊増 麻美, 中村 雄作, 八木 祐吏, 千田 麻友美, 木村 暁夫, 中尾 直樹, 武藤 多津郎, 山本 紘子, 佐橋 功, 西澤 正豊, 小野寺 理

    臨床神経学   46 ( 12 )   980 - 980   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症における睡眠時声門閉鎖率と嚥下障害の臨床的相関

    小澤 鉄太郎, 篠田 秀夫, 大瀧 祥子, 下畑 享良, 寺島 健史, 谷口 裕重, 他田 真理, 他田 正義, 横関 明男, 新保 淳輔, 五十嵐 修一, 小野寺 理, 田中 恵子, 西澤 正豊

    臨床神経学   46 ( 12 )   1083 - 1083   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 脂溶性および水溶性statinがアミロイド産生に及ぼす効果についての検討

    池内 健, 金子 博之, 須藤 晶子, 小野寺 理, 西澤 正豊

    臨床神経学   46 ( 12 )   1045 - 1045   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • アプラタキシンのRNAに対する機能の解析

    横関 明男, 他田 正義, 小山 哲秀, 志賀 篤, 高橋 哲哉, 五十嵐 修一, 西澤 正豊, 小野寺 理

    臨床神経学   46 ( 12 )   1148 - 1148   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症早期死亡例の臨床病理学的検討

    他田 真理, 柿田 明美, 小野寺 理, 西澤 正豊, 高橋 均

    臨床神経学   46 ( 12 )   1134 - 1134   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Aprataxinは損傷一本鎖DNAの3'-ブロックを解除する

    他田 正義, 高橋 哲哉, 五十嵐 修一, 横関 明男, 志賀 篤, 小山 哲秀, 伊達 英俊, 辻 省次, 西澤 正豊, 小野寺 理

    臨床神経学   46 ( 12 )   1111 - 1111   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • puratrophin-1遺伝子異常を認めた遺伝性SCD 3例に対するTRH低用量間歇療法の検討

    小倉 誉子, 上田 真努香, 三原 貴照, 池内 健, 野倉 一也, 山本 紘子, 小野寺 理, 武藤 多津郎

    臨床神経学   46 ( 12 )   1086 - 1086   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 進行性核上性麻痺(PSP)及び皮質基底核変性症(CBD)とタウ遺伝子(MAPT)

    高野 弘基, 西澤 正豊, 高橋 均, 柿田 明美, 小野寺 理

    臨床神経学   46 ( 12 )   1119 - 1119   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 第8番染色体長腕に連鎖する成人発症良性遺伝性舞踏病

    原 賢寿, 下畑 享良, 三瓶 一弘, 河内 泉, 金澤 雅人, 春日 健作, 宮下 哲典, 桑野 良三, 辻 省次, 小野寺 理, 西澤 正豊, 本間 義章

    臨床神経学   46 ( 12 )   1119 - 1119   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 小児大脳型ALDに対する造血幹細胞移植の治療効果のMRIによる検討

    小野寺 理, 辻 省次, 鈴木 康之, 加藤 俊一, 加藤 剛二, 加我 牧子, 西澤 正豊, 運動失調症に関する調査研究班副腎白質ジストロフィーの治療法開発のための臨床的及び基礎的研究班

    臨床神経学   46 ( 12 )   1161 - 1161   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 伸長ポリグルタミン鎖は核外移行の遅延により核内に蓄積する

    高橋 俊昭, 柴田 朋子, 小野寺 理, 西澤 正豊

    臨床神経学   46 ( 12 )   1148 - 1148   2006.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 頭痛の遺伝子研究の現状と展望 家族性片麻痺性片頭痛

    小野寺 理, 五十嵐 修一, 高橋 哲哉, 池内 健, 西澤 正豊

    日本頭痛学会誌   33 ( 2 )   49 - 49   2006.11

     More details

    Language:Japanese   Publisher:(一社)日本頭痛学会  

    researchmap

  • 【白質脳症update】 Vanishing white matter disease

    大竹 弘哲, 小野寺 理

    神経内科   65 ( 5 )   440 - 443   2006.11

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 当院における第16番染色体関連優性遺伝性脊髄小脳変性症4症例の臨床像と神経生理学的所見

    阪本 光, 山田 郁子, 中村 雄作, 池内 健, 小野寺 理

    臨床神経生理学   34 ( 5 )   397 - 397   2006.10

     More details

    Language:Japanese   Publisher:(一社)日本臨床神経生理学会  

    researchmap

  • α-Synuclein遺伝子重複を認めた遺伝性Lewy小体病の分子遺伝学および生化学的解析

    志賀 篤, 池内 健, 春日 健作, 金子 博之, 譚 春鳳, 柿田 明美, 高橋 均, 西澤 正豊, 小野寺 理, 石川 厚

    Dementia Japan   20 ( 2 )   169 - 169   2006.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 当院で経験した第16番染色体関連優性遺伝性脊髄小脳変性症4症例の臨床像と神経生理学的所見

    中村 雄作, 山田 郁子, 阪本 光, 池内 健, 小野寺 理

    臨床神経学   46 ( 8 )   595 - 595   2006.8

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 遺伝性Lewy小体病を表現型としたpresenilin-1変異(ΔT440)によるin vivoおよびin vitroにおけるα-synuclein蓄積の検討

    金子 博之, 池内 健, 石川 厚, 柿田 明美, 宮下 哲典, 桑野 良三, 伊藤 弦太, 岩坪 威, 高橋 均, 西澤 正豊, 小野寺 理

    Dementia Japan   20 ( 2 )   168 - 168   2006.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • Presenilin/γ-secretaseによるインスリン受容体の切断および細胞内局在に及ぼす影響

    春日 健作, 池内 健, 金子 博之, 小山 哲秀, 西澤 正豊, 小野寺 理

    Dementia Japan   20 ( 2 )   172 - 172   2006.8

     More details

    Language:Japanese   Publisher:(一社)日本認知症学会  

    researchmap

  • 【ミトコンドリア病】 ミトコンドリア異常とその他の疾患 Friedreich失調症

    小野寺 理

    Clinical Neuroscience   24 ( 6 )   692 - 693   2006.6

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 標準治療と最新治療 メリット・デメリット 副腎白質ジストロフィー

    小野寺 理

    Clinical Neuroscience   24 ( 6 )   710 - 711   2006.6

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 【脊髄小脳変性症研究の最近の進歩】 脊髄小脳変性症の病態機序 ポリグルタミン病の治療戦略について

    高橋 俊昭, 小野寺 理

    神経研究の進歩   50 ( 3 )   457 - 463   2006.6

     More details

  • 【分子メカニズムから解き明かす疾患のサイエンス】 神経変性疾患 神経変性疾患における転写障害

    他田 正義, 小野寺 理

    実験医学   24 ( 10 )   1576 - 1583   2006.6

     More details

    Language:Japanese   Publisher:(株)羊土社  

    近年,脊髄小脳変性症のなかで,優性遺伝性の大部分を占めるポリグルタミン病や,劣性遺伝性神経変性疾患のうちDNA修復機構の障害により生じる疾患において,転写障害が疾患の病態に深く関連することが示されている.転写障害が選択的神経細胞死を誘導する分子病態機序に関しては,不明の点が多く残されている.しかし,転写障害の改善を標的とした,神経変性疾患全般に応用可能な治療法開発の可能性を秘めている点で,この病態機序の研究は大変意義深い.本稿では転写障害が関与すると考えられる遺伝性神経変性疾患について解説する(著者抄録)

    researchmap

  • 【神経疾患に対する移植療法】 小児大脳型副腎白質ジストロフィー症の造血幹細胞移植療法

    小野寺 理

    神経内科   64 ( 5 )   511 - 517   2006.5

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are associated with the 5 ' region of the tau gene in Japanese, an H1 only population

    H Takano, M Nishizawa, O Onodera, A Kakita, H Takahashi

    NEUROLOGY   66 ( 5 )   277 - 277   2006.3

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • Predonisolone・cyclophosphamideの内服併用療法が奏効した,肥厚性硬膜炎をともなうmultifocal fibrosclerosisの1例

    他田 正義, 小野寺 理, 原 賢寿, 田中 恵子, 高橋 均, 辻 省次, 西澤 正豊

    臨床神経学   46 ( 2 )   128 - 133   2006.2

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    症例は54歳の男性で,発熱と咳嗽,上肢・体幹の隆起性紅斑で発症した.間質性肺炎と環状肉芽腫症と診断され,ステロイドパルス療法により症状は軽快したが,2ヵ月後に上強膜炎,滲出性中耳炎,副鼻腔炎,肥厚性硬膜炎を併発した.原疾患は特定されず,一方,組織学的に多臓器の高度の線維化と炎症細胞浸潤をともなう非特異的な慢性炎症性病変をみとめ,multifocal fibrosclerosis(MF)と診断した.ステロイドパルス療法やシクロフォスファミド(CP)パルス療法は効果が乏しかったが,副腎皮質ステロイド薬とCP内服の併用療法が奏功した.肥厚性硬膜炎をともなうMFの難治例では,CP内服併用療法も考慮すべきであると考えられた(著者抄録)

    researchmap

  • Puratrophin‐1遺伝子5’UTRのC→T置換を伴う脊髄小脳変性症の臨床遺伝子的検討

    NOZAKI HIROAKI, IKEUCHI KEN, KAWAKAMI AKIO, SHIMBO ATSUSUKE, HARA MASATOSHI, TOYOMASU ASAMI, NAKAMURA YUSAKU, YAGI YUUSHI, SENDA MAYUMI, KIMURA AKIO, NAKAO NAOKI, MUTO TATSURO, YAMAMOTO HIROKO, SAHASHI ISAO, NISHIZAWA MASATOYO, ONODERA OSAMU

    日本神経学会総会プログラム・抄録集   47th   99   2006

     More details

    Language:Japanese  

    J-GLOBAL

    researchmap

  • Aprataxin, the causative gene product for AOA1/EAOH, repairs damaged 3'-ends of DNA single strand breaks

    M. Tada, T. Takahashi, S. Igarashi, A. Yokoseki, H. Date, S. Tsuji, M. Nishizawa, O. Onodera

    MOVEMENT DISORDERS   21   S339 - S339   2006

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • Multiple system atrophy: Morphometric evaluation of the CNS autonomic nuclei in patients with sudden deaths

    M. Tada, A. Kakita, O. Onodera, M. Nishizawa, H. Takahashi

    MOVEMENT DISORDERS   21   S535 - S535   2006

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 多系統萎縮症における睡眠時声門閉鎖率解析

    小澤 鉄太郎, 篠田 秀夫, 中山 秀章, 下畑 享良, 寺島 健史, 他田 真理, 他田 正義, 横関 明男, 新保 淳輔, 五十嵐 修一, 小野寺 理, 田中 恵子, 西澤 正豊

    臨床神経学   45 ( 12 )   1166 - 1166   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Frontotemporal dementiaを表現型とするpresenilin1変異体の分子病態

    池内 健, 須藤 晶子, 金子 博之, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 12 )   1006 - 1006   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 進行性核上性麻痺PSPとタウ遺伝子の関連

    高野 弘基, 西澤 正豊, 高橋 均, 柿田 明美, 小野寺 理

    臨床神経学   45 ( 12 )   1099 - 1099   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PS1遺伝子変異によりレビー小体型痴呆と変異型アルツハイマー病を合併した1家系

    石川 厚, 朴 月善, 宮下 哲典, 桑野 良三, 小野寺 理, 西澤 正豊, 高橋 均

    臨床神経学   45 ( 12 )   1097 - 1097   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 増大ポリグルタミン鎖発現に伴う細胞内蛋白挙動の解析

    長谷川 有香, 高橋 俊昭, 豊島 靖子, 小野寺 理, 吉田 豊, 西澤 正豊

    臨床神経学   45 ( 12 )   1101 - 1101   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 伸長ポリグルタミンによるCREB依存性転写活性化障害の個体レベルでの検証

    高野 政彦, 赤岩 靖久, 佐藤 俊哉, 小宅 睦郎, 小野寺 理, 西澤 正豊, 辻 省次

    臨床神経学   45 ( 12 )   1101 - 1101   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン鎖の長さ依存性に認められる核内蓄積機序の検討

    小野寺 理, 高橋 俊昭, 辻 省次, 西澤 正豊

    臨床神経学   45 ( 12 )   1048 - 1048   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 遺伝子異常未同定の常染色体優性脊髄小脳変性症(ADSCD)の臨床像の検討

    新保 淳輔, 原 賢寿, 池内 健, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 12 )   1034 - 1034   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン鎖のオリゴマー形成を生細胞で可視化する

    高橋 俊昭, 菊池 信矢, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 12 )   1077 - 1077   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • EAOH/AOA1の原因蛋白aprataxinはexonuclease活性を持つ

    高橋 哲哉, 五十嵐 修一, 他田 正義, 伊達 英俊, 高野 弘基, 小宅 睦朗, 辻 省次, 西澤 正豊, 小野寺 理

    臨床神経学   45 ( 12 )   1077 - 1077   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Aprataxin(APTX)の生理機能 細胞内局在の検討

    五十嵐 修一, 小山 哲秀, 高橋 哲哉, 高橋 俊昭, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 12 )   1103 - 1103   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 禿頭と変形性脊椎症を伴う劣性遺伝性白質脳症(CARASIL)の連鎖解析

    原 賢寿, 小野寺 理, 宮下 哲典, 福武 敏夫, 宮野 悟, 塩田 宏嗣, 田村 正人, 藤野 泰祐, 下江 豊, 平山 幹生, 有里 敬代, 柳川 宗平, 桑野 良三, 西澤 正豊, 辻 省次

    臨床神経学   45 ( 12 )   1147 - 1147   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • aprataxinはDNA修復において校正機能を担うのか?

    他田 正義, 高橋 哲哉, 五十嵐 修一, 志賀 篤, 小山 哲秀, 高野 弘基, 小宅 睦朗, 池内 健, 辻 省次, 西澤 正豊, 小野寺 理

    臨床神経学   45 ( 12 )   1103 - 1103   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 大脳白質病変の重症度とMRAによる頭蓋内血管病変との相関

    金澤 雅人, 三瓶 一弘, 赤岩 靖久, 小野寺 理, 他田 正義, 川村 邦雄, 春日 健作, 高野 弘基, 西澤 正豊

    臨床神経学   45 ( 12 )   1155 - 1155   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 病理学的に確認された多系統萎縮症49例の臨床像の検討

    他田 真理, 小野寺 理, 小澤 鉄太郎, 他田 正義, 朴 月善, 高橋 均, 西澤 正豊

    臨床神経学   45 ( 12 )   1167 - 1167   2005.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経変性疾患の最新の病因・病態解析 DNA修復障害と神経変性 核酸品質管理の破綻と神経変性

    小野寺 理

    臨床神経学   45 ( 11 )   979 - 981   2005.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 禿頭と変形性脊椎症を伴う劣性遺伝性白質脳症(CARASIL)の連鎖解析

    原 賢寿, 小野寺 理, 宮下 哲典, 福武 敏夫, 宮野 悟, 塩田 宏嗣, 田村 正人, 藤野 泰祐, 下江 豊, 平山 幹生, 有里 敬代, 柳川 宗平, 桑野 良三, 西澤 正豊, 辻 省次

    新潟医学会雑誌   119 ( 11 )   695 - 695   2005.11

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 【遺伝子からみた非アルツハイマー型認知症(痴呆)】 レビー小体型認知症(痴呆)とβシヌクレイン

    大竹 弘哲, 小野寺 理

    Cognition and Dementia   4 ( 4 )   290 - 294   2005.10

     More details

    Language:Japanese   Publisher:(株)メディカルレビュー社  

    レビー小体型認知症(痴呆)(DLB)の家系においてαシヌクレイン(SNCA)の変異と重複が指摘されたことや,SNCAがレビー小体の主な構成要素であることなどから,SNCAがDLBの病態に関係していると考えられている.一方,βシヌクレイン(SNCB)はSNCAと相同性が高く,SNCAの凝集体形成を抑制するとされる.この特性から,SNCBに関連したDLB発症機序が推察されていた.2004年,筆者らはDLB症例でSNCBのアミノ酸置換(V70MとP123H)を伴う,一塩基置換を報告した.これらの症例では家系内での検討がなされていないため,この意義づけには慎重な検討が必要である.しかし,本変異部位が種間,ファミリー蛋白間で保存されている領域にあり,多数の対照例における検討にて同じ一塩基置換を認めないことなどから,SNCBを介したDLB発症機序を示唆する症例と考えた(著者抄録)

    researchmap

  • 生細胞における可溶性ポリグルタミン二量体の可視化(Visualization of soulble Polyglutamine dimer in Living cell)

    高橋 俊昭, 菊池 信矢, 小野寺 理, 西澤 正豊

    神経化学   44 ( 2-3 )   198 - 198   2005.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • 脊髄小脳変性症はapratoxinというタンパク質をつくるが,これは3'-5'エキソヌクレアーゼである(Spinocerebellar degeneration caused protein, aprataxin, is a 3'-5' exonuclease)

    他田 正義, 高橋 哲哉, 五十嵐 修一, 伊達 英俊, 小山 哲秀, 志賀 篤, 高野 弘基, 小宅 睦郎, 辻 省次, 西澤 正豊, 小野寺 理

    神経化学   44 ( 2-3 )   198 - 198   2005.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • PABPN1遺伝子(GCG)8のヘテロ変異が同定された老年期発症の眼咽頭筋ジストロフィーの1例

    徳武 孝允, 池内 健, 田中 惠子, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 6 )   437 - 440   2005.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    72歳女性.患者は階段の昇降困難,眼瞼下垂,固形物嚥下時のむせが徐々に進行し,入院となった.所見では,両側眼瞼下垂,両側眼球の上転・外転制限,開鼻声,嚥下障害,上下肢近位筋・頸筋主体の筋力低下を認め,CK,Caの軽度高値を認めた.針筋電図では大腿直筋,舌,咬筋に低振幅・短持続性の運動単位を認め,骨格筋CTでは傍脊柱筋,大臀筋,下肢屈筋群に虫食い像を認めた.更に左大腿外側広筋の生検で,筋線維の大小不同と少数のrimmed vacuoleを認めたが,炎症細胞浸潤は認めなかった.眼咽頭筋ジストロフィー(OMPD)を疑って白血球ゲノムDNAを用いたPABPN1遺伝子解析を行なったところ,PABPN1遺伝子(GCG)8リピートのOMPDと確定診断された

    researchmap

  • 【脊髄小脳変性症の話題】 臨床の現場から

    小野寺 理

    難病と在宅ケア   11 ( 2 )   11 - 14   2005.5

     More details

    Language:Japanese   Publisher:(株)日本プランニングセンター  

    researchmap

  • A pedigree of Charcot-Marie-Tooth disease type 4F (Periaxin mutation)

    Mitsuteru Shimohata, Kiyoshi Hirahara, Shuichi Igarashi, Kenju Hara, Kazuki Kijima, Osamu Onodera, Keiko Tanaka, Masatoyo Nishizawa, Shoji Tsuji, Kiyoshi Hayasaka

    Clinical Neurology   45 ( 3 )   221 - 225   2005.3

     More details

    Language:Japanese  

    We report a 51-year-old man genetically diagnosed as Charcot-Marie-Tooth disease type 4F. The patient was the first child of healthy, consanguineous parents. He had two sisters and one of them showed similar but milder symptoms. He had gait disturbance since childhood. Then he noticed muscle weakness of his hands at the age of early forties, and more difficulties in gait at the age of late forties. On examination at age 51, he showed absence of all deep tendon reflexes, weakness of the hand and distal leg muscles, pes cavus and decreased sensitivity to touch and vibration in the lower extremities. Electrophysiological studies of the median nerve showed delayed motor nerve conduction velocity and undetectable sensory nerve action potentials. The histology of his sural nerve revealed moderate loss of large myelinated fibers and the diameters of residual fibers shifted to small shown as size-frequency histogram. Many fibers are thinly myelinated and some of the Schwann cells looked as wrapping around the myelinate fibers with their processes. On gene analyses, we identified an Arg 1070 Stop homozygous mutation in the Periaxin, known to be a causative gene for CMT type 4F. Based on these observations, we emphasized that broad genetic analyses are necessary for diagnosis of CMT disease, including so far unidentified mutations among the Japanese populations.

    Scopus

    PubMed

    researchmap

  • 脊髄小脳変性症の分子遺伝学

    小野寺 理

    臨床神経学   45 ( 3 )   258 - 258   2005.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Spinocerebellar ataxia type 2(SCA2)における前頭葉機能障害と3D-SSP SPECT所見

    下畑 享良, 松澤 陽子, 田中 孔明, 小野寺 理, 田中 惠子, 西澤 正豊

    臨床神経学   45 ( 1 )   22 - 26   2005.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    症例1(47歳男性).歩行時のふらつきを主訴とした.病態認知機能障害と著明なGegenhaltenを認めた.症例2(35歳女性).歩行時のふらつき,開眼困難を主訴とし,感情失禁を認めた.両症例とも,長谷川式簡易機能評価スケール,Mini Mental State Examinationでは明らかな異常を認めなかったが,WAIS-RやWisconsin card sorting testでは明らかに知能低下と遂行機能障害の存在が示唆された.頭部MRIでは共に大脳萎縮は認めなかったが,three-dimensional stereotactic surface projection(3D-SSP)SPECTでは小脳・脳幹および両側前頭葉の血流低下を認めた.以上により,SCA 2では比較的早期から前頭葉機能障害を呈することが示された.また3D-SSP SPECTは,その評価法として有用と考えられた

    researchmap

  • 不随意運動と痴呆で発症したspinocerebellar ataxia type 17(SCA17)の一例

    横関 明男, 中島 孝, 川上 英孝, 小野寺 理, 西澤 正豊

    臨床神経学   45 ( 1 )   52 - 52   2005.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CARASIL, autosomal recessive vascular dementia with alopecia and spondylosis deformans maps to chromosome 10q

    K Hara, O Onodera, T Fukutake, S Miyano, H Shioda, Y Fujino, Y Shimoe, M Hirayama, T Arisato, S Yanagawa, S Ikeda, A Miyashita, R Kuwano, M Nishizawa, S Tsuji

    ANNALS OF NEUROLOGY   58   S57 - S57   2005

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 多系統萎縮症(MSA)におけるsynuclein関連遺伝子の一塩基多型(SNP)解析

    大竹 弘哲, 小野寺 理, 柿田 明美, 長谷川 有香, 五十嵐 修一, 小澤 鉄太郎, 奥泉 薫, 辻 省次, 高橋 均, 西澤 正豊

    臨床神経学   44 ( 12 )   1157 - 1157   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Aprataxinの機能解析 一本鎖DNA修復関連蛋白との相互作用

    五十嵐 修一, 伊達 英俊, 高橋 俊昭, 高橋 哲哉, 高野 弘基, 小宅 睦郎, 佐野 泰照, 辻 省次, 小野寺 理, 西澤 正豊

    臨床神経学   44 ( 12 )   1090 - 1090   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • プロリン残基挿入による異常伸長ポルグルタミン鎖の凝集体形成・細胞毒性の抑制

    ポピエル ヘレナ明子, 永井 義隆, 小野寺 理, 乾 隆, 藤掛 伸宏, 裏出 良博, 戸田 達史

    臨床神経学   44 ( 12 )   1090 - 1090   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 進行性核上麻痺とタウ遺伝子領域の関連

    高野 弘基, 小野寺 理, 柿田 明美, 高橋 均, 西澤 正豊

    臨床神経学   44 ( 12 )   1152 - 1152   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • APTX P206Lホモ接合体の兄妹例(EAOHの臨床的多様性について)

    丸田 恭子, 園田 至人, 福永 秀敏, 木脇 隆史郎, 梅原 藤雄, 伊達 英俊, 小野寺 理

    臨床神経学   44 ( 12 )   1129 - 1129   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • EAOH/AOA1の臨床症状の検討

    小野寺 理, 横関 明男, 伊達 英俊, 五十嵐 修一, 西澤 正豊, 辻 省次

    臨床神経学   44 ( 12 )   1158 - 1158   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 多系統萎縮症(MSA)におけるsynuclein関連遺伝子の一塩基多型(SNP)解析

    大竹 弘哲, 小野寺 理, 柿田 明美, 長谷川 有香, 五十嵐 修一, 小澤 鉄太郎, 奥泉 薫, 高橋 均, 辻 省次, 西澤 正豊

    新潟医学会雑誌   118 ( 12 )   714 - 714   2004.12

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 本邦初と思われるCMT4F一家系例の臨床,組織学的所見および遺伝子異常について

    下畑 光輝, 原 賢寿, 五十嵐 修一, 小野寺 理, 田中 恵子, 西澤 正豊, 辻 省次, 木島 一己, 沼倉 周彦, 早坂 清

    臨床神経学   44 ( 12 )   1203 - 1203   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • APTXノックアウトマウスによるEAOHのモデル動物の作成

    小宅 睦郎, 小野寺 理, 五十嵐 修一, 伊達 英俊, 高橋 哲哉, 高野 弘基, 辻 省次, 西澤 正豊

    臨床神経学   44 ( 12 )   1198 - 1198   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 家族性多系統萎縮症のnon-parametric連鎖解析

    原 賢寿, 小野寺 理, 西澤 正豊, 宮下 哲典, 桑野 良三, 山田 光則, 高橋 均, 登木口 進, 平澤 基之, 水野 美邦, 後藤 順, 辻 省次

    臨床神経学   44 ( 12 )   1193 - 1193   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • EAOH/AOA1の原因遺伝子アプラタキシン(APTX)の機能解析

    高橋 哲哉, 五十嵐 修一, 伊達 英俊, 高野 弘基, 辻 省次, 小野寺 理, 西澤 正豊

    臨床神経学   44 ( 12 )   1198 - 1198   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 伸長ポリグルタミン鎖の長さ依存性を持った核内集積の検討

    高橋 俊昭, 小野寺 理, 辻 省次, 西澤 正豊

    臨床神経学   44 ( 12 )   1197 - 1197   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 孤発性純粋タウオパチーとタウ遺伝子領域の関連

    高野 弘基, 西澤 正豊, 小野寺 理, 柿田 明美, 高橋 均

    新潟医学会雑誌   118 ( 12 )   713 - 714   2004.12

     More details

    Language:Japanese   Publisher:新潟医学会  

    researchmap

  • 成人型leukoencephalopathy with vanishing white matter(VWM)の臨床的検討

    松井 大, 水谷 江太郎, 小林 邦子, 三木 幸雄, 石津 浩一, 福山 秀直, 大竹 弘哲, 下畑 享良, 小野寺 理, 高山 吉弘, 柴崎 浩

    臨床神経学   44 ( 12 )   1076 - 1076   2004.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【ポストゲノム時代の神経疾患の分子遺伝学】 感覚神経細胞とPurkinje細胞に共通する神経変性の原因はあるのか-常染色体劣性遺伝性脊髄小脳変性症の解明から学ぶこと

    小野寺 理

    神経研究の進歩   48 ( 5 )   751 - 760   2004.10

     More details

    Language:Japanese   Publisher:(株)医学書院  

    劣性遺伝性脊髄小脳変性症は,後根神経節の感覚神経細胞,もしくは小脳のPurkinje細胞に変性の主体がある疾患群である.判明した原因遺伝子は多岐に及ぶが,代表的なものの分類を試みると,1)膜における酸化ストレス調節の障害に関するもの,2)酸化ストレスに対するミトコンドリアの機能異常に関するもの,3)核DNAの修復障害に関するものに分類される.感覚神経細胞の障害は数年にわたり進行性であり,蓄積された障害により神経変性が引き起こされると推察される.一方,Purkinje細胞の変性の程度は強弱があり,核DNAの修復障害に問題がある例に強い.核DNAの修復障害では一本鎖DNA修復,とくに塩基除去修復との関連が注目されている

    DOI: 10.11477/mf.1431100232

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2005100600

  • 神経変性疾患克服へ向けて 若手研究者たちの挑戦 神経変性を引き起こす蛋白APTXはDNAを修復する(Toward establishing therapies for neurodegenerative diseases: Challenges by young investigators: Neurodegenerative disease protein,APTX,is a new DNA repair protein)

    小野寺 理

    神経化学   43 ( 2-3 )   326 - 326   2004.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • Spinocerebellar ataxia type 17 repeat in patients with Huntington's disease-like and ataxia - Reply

    Y Toyoshima, M Yamada, O Onodera, M Shimohata, C Inenaga, N Fujita, M Morita, S Tsuji, H Takahashi

    ANNALS OF NEUROLOGY   56 ( 1 )   163 - 164   2004.7

     More details

    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:WILEY-LISS  

    DOI: 10.1002/ana.20145

    Web of Science

    researchmap

  • cyclophosphamide(CPA)内服が奏効した,肥厚性硬膜炎を伴うmultifocal fibrosclerosis(MF)の1例

    他田 正義, 小野寺 理, 原 賢寿, 田中 恵子, 西澤 正豊, 辻 省次

    臨床神経学   44 ( 7 )   462 - 462   2004.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 20代で発症し,きわめて軽症と考えられた低アルブミン血症と眼球運動失行を伴う早発型運動失調症(EAOH)の1例

    鈴木 千恵子, 田野崎 真人, 前田 哲也, 木村 珠喜, 新井 陽, 大和 博, 冨山 誠彦, 神成 一哉, 馬場 正之, 松永 宗雄, 小野寺 理, 上條 美樹子

    臨床神経学   44 ( 7 )   475 - 475   2004.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【遺伝性脊髄小脳変性症 遺伝子未解明の疾患を中心に】 Hypogonadismを伴う小脳失調症

    他田 正義, 小野寺 理, 藤田 信也, 永井 博子, 西澤 正豊

    神経内科   60 ( 5 )   512 - 519   2004.5

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【遺伝性脊髄小脳変性症 遺伝子未解明の疾患を中心に】 常染色体劣性遺伝性脊髄小脳変性症

    小野寺 理

    神経内科   60 ( 5 )   497 - 505   2004.5

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【遺伝性脊髄小脳変性症 遺伝子未解明の疾患を中心に】 アプラタキシンP206Lホモ接合体の兄妹例 EAOHの臨床的多様性について

    丸田 恭子, 園田 至人, 小野寺 理, 木脇 隆史郎, 福永 秀敏

    神経内科   60 ( 5 )   520 - 528   2004.5

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    アプラタキシン・ミスセンス変異(P206L)ホモ接合体が確認されたEAOH(early-onset ataxia with ocular motor apraxia and hypoalbuminemia)の兄妹症例(66歳,60歳)の臨床的特徴について検討し,同じミスセンス変異をもつ日本の2家系3症例の臨床症状との比較検討を行った.その結果,自験例2例はともに16歳時に小脳失調による歩行困難で発症,緩徐進行性の小脳症状と末梢神経障害を主徴とし,小脳性構音障害・水平注視眼振・上肢の企図振戦・四肢体幹の失調に加え高度な四肢遠位部の筋萎縮と筋力低下,感覚低下と深部腱反射消失を認めた.自験例と同じ変異をもつ3症例は22歳男性例と兄弟例(31歳,26歳)で,これらミスセンス変異5症例ではフレームシフト変異症例に比べて知能障害を認めず進行が緩徐で,同一家系内でも臨床症状や経過にはバラツキがみられた.特に自験例の60歳女性例では歩行不能年齢が40歳と他の4症例の20〜24歳より遅く,66歳男性例では眼球運動障害と無緊張性膀胱を認めた点が特異であった

    researchmap

  • Effects of vocal cord abductor paralysis evaluated by propofol-induced sleep laryngoscopy on sleep-related respiratory dysfunction in multiple system atrophy (MSA)

    T Shimohata, H Shinoda, H Nakayama, K Terajima, T Ozawa, O Onodera, M Nishizawa

    NEUROLOGY   62 ( 7 )   A507 - A508   2004.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

    researchmap

  • 多系統萎縮症と自律神経障害 多系統萎縮症の突然死の病態の解明,および治療法の確立を目指して

    下畑 享良, 中山 秀章, 篠田 秀夫, 小野寺 理, 西澤 正豊

    自律神経   41 ( 2 )   161 - 166   2004.4

     More details

    Language:Japanese   Publisher:日本自律神経学会  

    多系統萎縮症(MSA)における突然死の原因として声帯開大不全などの睡眠呼吸障害の関与が指摘されている.MSA16症例に対して施行した血液ガス,呼吸機能検査,ポリソムノグラフィー(PSG),睡眠下喉頭内視鏡検査の成績を紹介した.血液ガスにおけるAaDO2の開大とPSGにおけるREM期の割合の減少は,罹病期間と有意な相関を認めた.また,声帯開大不全の有無により分けた2群間で,小脳失調重症度スコア,罹病期間,血液ガス,無呼吸指数等のPSG所見に有意差を認めなかった

    researchmap

  • EAOH(眼球運動失行と低アルブミン血症を伴う早発型失調症)の末梢神経障害

    小野寺 理, 横関 明男, 伊達 英俊, 佐野 泰照, 五十嵐 修一, 辻 省次

    厚生労働省精神・神経疾患研究総括研究報告 遺伝性ニューロパチーの診断システムの確立および治療に関する研究   ( 平成13〜15年度 )   49 - 49   2004.3

     More details

    Language:Japanese   Publisher:厚生労働省精神・神経疾患研究班  

    劣性遺伝形式をとる小脳失調症の中にはDNA修復機構異常症と考えられる一群が存在することが明らかとなってきている.そこで,DNA修復機構異常が末梢神経障害に与える影響に関して考察した.aprataxin(APTX)変異の明らかとなった27家系42例の臨床像をretrospectiveに検討した.早発型失調症における軸索変性型のneuropathyのAPTX変異と時間軸にそった変性過程を明らかになった.その程度は極めて高度で,臨床症状の中核をなした.またLAPTXが主体であり細胞内局在は核であることを明らかになった.本蛋白の発現量の低下が,発症と関連していることが示唆された.さらにXRCC1との結合を認めた

    researchmap

  • 兵庫県出身のSCA-17の1例

    川端 啓太, 高岡 俊雄, 武田 正中, 立花 久大, 芳川 浩男, 小野寺 理

    臨床神経学   44 ( 3 )   220 - 220   2004.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 舞踏運動を呈した症例に対する分子遺伝学的解析

    下畑 享良, 小野寺 理, 本間 義章, 廣田 紘一, 布村 仁一, 木村 哲也, 河内 泉, 三瓶 一弘, 西澤 正豊, 辻 省次

    臨床神経学   44 ( 3 )   149 - 153   2004.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    舞踏病あるいはハンチントン病(HD)疑い79例(男34例,女45例,平均48.8歳)に対し遺伝子診断を行った.家族歴ありは37家系39例(A群),なしは40例(B群)であった.A群の遺伝子解析では,HDが28家系29例,歯状核赤核淡蒼球ルイ体萎縮症(DRPLA)が5家系5例であった.ハンチントン病類縁疾患1型(HDL1),2型(HDL2),遺伝性脊髄小脳変性症17型(SCA17)はなかった.残り4家系は常染色体優性遺伝形式と考えられた2家系3例と,両親が血族結婚の2家系2例であった.B群ではHDが8例,DRPLAが2例で,HDL1,2,SCA17は認めず,診断不明が20例であった.HDの37例では,原因遺伝子の伸長アリルのCAGリピート数と発症年齢との間に負の相関を認めた.家族歴の有無により発症年齢,CAGリピート数に有意差はなかった.CAGリピート数49以上の7例の臨床症状は,腱反射亢進4例,小脳性運動失調3例,眼球運動障害2例,ジストニア1例と多彩であった.DRPLAの7例のCAGリピート数は平均65.8で,小脳性運動失調を2例に認めた

    researchmap

  • 虚血性白質病変の感受性遺伝子同定に向けたMRIによる白質病変パターン分類の試み

    赤岩 靖久, 他田 正義, 川村 邦雄, 春日 健作, 三瓶 一弘, 高野 弘基, 小野寺 理, 西澤 正豊

    脳卒中   26 ( 1 )   255 - 255   2004.3

     More details

    Language:Japanese   Publisher:(一社)日本脳卒中学会  

    researchmap

  • 遺伝性ニューロパチーの診断システムの確立および治療に関する研究

    祖父江 元, 早坂 清, 佐古田 三郎, 有村 公良, 岡 伸幸, 山村 隆, 松村 喜一郎, 小野寺 理, 池田 修一, 安東 由紀雄, 馬場 正之, 中里 雅光, 安田 斎, 斎藤 豊和, 池中 一裕, 古谷 博和, 和田 圭司, 中島 健二, 渡部 和彦, 安東 えい子, 梶 龍児, 中川 正法

    厚生労働省精神・神経疾患研究総括研究報告 遺伝性ニューロパチーの診断システムの確立および治療に関する研究   ( 平成13〜15年度 )   1 - 3   2004.3

     More details

    Language:Japanese   Publisher:厚生労働省精神・神経疾患研究班  

    慢性炎症性脱髄性多発神経炎(CIDP)のIVIg療法の反応性を規定する臨床病理学的および遺伝的因子背景を全国調査から検索した.Chrcot-Marie-Tooth病(CMT),遺伝性圧脆弱性ニューロパチー(HNPP),家族性アミロイドポリニューロパチー(FAP)を対象疾患として,全国アンケート調査を行い,本邦の遺伝性ニューロパチーの実態の把握とともにDNAサンプルの集積を行った.その結果,我が国の特徴と実態が明らかになった.CIDPのIVIg療法に対するnon-responderを規定する臨床的因子して,筋萎縮,慢性経過,四肢CMAPの低下,正中神経MCVの遅延が有意に関与していた.マイクロアレイによる遺伝子発現解析では,TNAα superfamilyなどの免疫系に関与するサイトカインがnon-responder群で有意に高発現を示した.軸索の脆弱性がIVIg療法反応性に関与している可能性が考えられた

    researchmap

  • 眼球運動失行と低アルブミン血症をともなう早発型脊髄小脳失調症:末梢神経障害の長期経過

    鈴木 千恵子, 田野崎 真人, 馬場 正之, 上條 美樹子, 小野寺 理

    厚生労働省精神・神経疾患研究総括研究報告 遺伝性ニューロパチーの診断システムの確立および治療に関する研究   ( 平成13〜15年度 )   31 - 31   2004.3

     More details

    Language:Japanese   Publisher:厚生労働省精神・神経疾患研究班  

    46歳女.若年発症脊髄小脳変性症の末梢神経障害合併例として経過観察していた.その後,失調症状は徐々に進行し,34歳時から杖歩行,38歳時に書字困難が出現,40歳時から車椅子を使用開始,46歳時には著明な失調症状のため立位保持不能となった.再入院し再評価を行った.遺伝子検索を施行し,早発型脊髄小脳失調症と確定診断した

    researchmap

  • EAOH原因遺伝子APTXの生理機能の解明 DNA修復障害と神経変性との関連

    小野寺 理, 五十嵐 修一, 佐野 泰照, 伊達 英俊, 高橋 俊昭, 高橋 哲哉, 横関 明男, 西澤 正豊, 辻 省次

    厚生労働省精神・神経疾患研究総括研究報告 遺伝性ニューロパチーの診断システムの確立および治療に関する研究   ( 平成13〜15年度 )   28 - 28   2004.3

     More details

    Language:Japanese   Publisher:厚生労働省精神・神経疾患研究班  

    眼球運動失行と低アルブミン血症を伴う早発型失調症の原因遺伝子aprataxin(APTX)を単離しその臨床型について報告した.APTXの生理機能について検討し,DNA修復に関連する蛋白である可能性が推察された.生理機能からDNA修復機構異常が末梢神経障害に与える影響について検討した.long及びshot formのAPTX(LAPTX,SPATX)に対するスクリーニングを胎児脳由来のライブラリーを対象として行った.LAPTXが主体で,細胞内局在は核であった.患者群ではその発現量が低下消失し,発現量の低下が,発症と関連していることが示唆された.SSBRに関連する諸蛋白の足場蛋白として働きその効率を増強することが知られているXRCC1との結合を見出した

    researchmap

  • Charcot-Marie-Tooth病4F型の一例

    木島 一己, 白幡 恵美, 沼倉 周彦, 早坂 清, 下畑 光輝, 原 賢寿, 西澤 正豊, 五十嵐 修一, 小野寺 理

    日本小児科学会雑誌   108 ( 2 )   182 - 182   2004.2

     More details

    Language:Japanese   Publisher:(公社)日本小児科学会  

    researchmap

  • Clinical analyses of 50 families of early-onset autosomal recessivespinocerebellar ataxias in the Japanese population

    M Tada, K Hara, O Onodera, H Date, S Tsuji, M Nishizawa

    MOVEMENT DISORDERS   19   S24 - S24   2004

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • Clinical features of 49 pathologically proven multiple system atrophy in the Japanese population

    M Tada, T Ozawa, O Onodera, M Tada, H Takahashi, M Nishizawa

    MOVEMENT DISORDERS   19   S24 - S24   2004

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 眼球運動失行,低アルブミン血症を伴う早発型失調症の原因蛋白aprataxinの解析

    佐野 泰照, 伊達 英俊, 五十嵐 修一, 小野寺 理, 小宅 睦郎, 高橋 俊昭, 高橋 均, 福原 信義, 巻淵 隆夫, 森松 光紀, 辻 省次

    臨床神経学   43 ( 12 )   1081 - 1081   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Lewy小体型痴呆(DLB)患者におけるbeta-及びgamma-synuclein(SNCB,SNCG)遺伝子変異

    大竹 弘哲, 小野寺 理, 五十嵐 修一, 斎藤 正明, 柿田 明美, 高橋 均, 石川 厚, 出塚 次郎, 若林 允甫, 戸田 達史, 辻 省次

    臨床神経学   43 ( 12 )   923 - 923   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 本邦における小児大脳型ALD(CCALD)例への造血幹細胞移植(HSCT)

    小野寺 理, 辻 省次, 鈴木 康之, 加藤 俊一, 加藤 剛二, 加我 牧子, 古谷 博和, 副腎白質ジストロフィーの治療法開発のための臨床的及び基礎的研究班

    臨床神経学   43 ( 12 )   934 - 934   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン病における転写障害assay系の確立

    高橋 俊昭, 野崎 兼吉, 小野寺 理, 辻 省次

    臨床神経学   43 ( 12 )   1082 - 1082   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 低アルブミン血症と眼球運動失行を伴う早発型失調症(EAOH)の臨床像42症例の検討

    横関 明男, 伊達 英俊, 小野寺 理, 西澤 正豊, 辻 省次, 岩淵 潔, 長友 秀樹, 関島 良樹, 池田 修一, 広井 正, 植川 和利, 粟屋 豊, 斎藤 加代子, 酒井 徹雄, 高橋 智

    臨床神経学   43 ( 12 )   999 - 999   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 本邦における舞踏病症例の遺伝子解析

    下畑 享良, 小野寺 理, 本間 義章, 木村 哲也, 河内 泉, 三瓶 一弘, 辻 省次

    臨床神経学   43 ( 12 )   1016 - 1016   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 拡散強調画像による多系統萎縮症の脳幹病変の検討

    金澤 雅人, 下畑 享良, 寺島 健史, 小野寺 理, 田中 恵子, 辻 省次, 岡本 浩一郎, 西澤 正豊

    臨床神経学   43 ( 12 )   1024 - 1024   2003.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Full-length DRPLA protein suppress CREB- and p53-dependent transcriptional

    T Shimohata, K Ogura, S Naruse, S Igarashi, T Sato, O Onodera, M Nishizawa, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   73 ( 5 )   550 - 550   2003.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • The analysis of polymorphisms of synuclein family genes in multiple system atrophy (MSA).

    H Ohtake, O Onodera, A Kakita, A Hasegawa, S Igarashi, T Ozawa, K Okuizumi, H Takahashi, S Tsuji, M Nishizawa

    AMERICAN JOURNAL OF HUMAN GENETICS   73 ( 5 )   469 - 469   2003.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • Aprataxin, the causative gene for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), is a member of SSDNA repair machinery. Implication of impaired DNA repair systems in neurodegeneration.

    H Date, S Igarashi, T Takahashi, H Takano, O Onodera, M Nishizawa, Y Sano, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   73 ( 5 )   546 - 546   2003.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • Analyses of biochemical function of aprataxin in DNA single-strand break repair.

    T Takahashi, S Igarashi, H Date, O Onodera, M Nishizawa, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   73 ( 5 )   551 - 551   2003.11

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • MRIで脳幹部の著明な腫脹と造影効果を認めMRAが診断に有用であった硬膜動静脈瘻の1例

    他田 正義, 小野寺 理, 志知 隆雄, 原 賢寿, 辻 省次

    神経内科   59 ( 5 )   515 - 520   2003.11

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    77歳女.頭痛,歩行時ふらつきを主訴とした.左眼窩部を中心とした頭痛で発症し,複視,左眼瞼充血,左眼瞼下垂,左眼球突出等が出現した.治療により症状は緩徐に軽快していたが約4ヵ月後には左眼症状に加えて右眼にも同様の症状とふらつき,構音障害が出現した.頭部MRIで脳幹部に著明な腫脹と造影効果が認められ,MRAでは,脳底動脈の左側に淡い異常信号域を認めた.三次元time-of-flight MRAの元画像で,脳底静脈叢の左側から左小脳橋槽にかけて一条の高信号を認め,左上錐体静脈洞を流出血管とする硬膜動静脈瘻と考えられた.症状は無治療で改善傾向を示した.初回から約2ヵ月後のMRIでは,脳幹部の腫脹と造影効果は消失し,MRAおよびその元画像では異常血流影は指摘できなかった.本例では長期にわたりその症状が左側から右側に移り変わったことが特徴的であった

    researchmap

  • 嚥下障害が初発症状であった全身型破傷風の2例

    金澤 雅人, 石黒 英明, 小野寺 理, 吉川 健二郎, 小出 隆司, 新井 亜希, 長谷川 有香, 中野 亮一, 田中 恵子, 西澤 正豊

    脳と神経   55 ( 11 )   973 - 976   2003.11

     More details

    Language:Japanese   Publisher:(株)医学書院  

    嚥下障害を初発症状とし,全身痙攣を伴わなかった軽症破傷風2例を経験した.症例1:60歳男.著明な開口制限,嚥下障害を認め,破傷風を疑われた.外傷は認めなかったが,開口制限,舌の運動障害,頸部痛を認め,全身型破傷風と診断された.絶飲食,室内暗室とし,破傷風免疫グロブリンを投与し,ペニシリンGの連日投与を開始した.第7病日より症状改善し,第13病日より食事を開始した.筋逸脱酵素が低下し,開口制限,嚥下障害が消失したため,破傷風トキソイドを投与し,退院した.症例2:76歳女.嚥下時に違和感を自覚した.開口制限,舌の運動障害,後頸部痛を認めるため,全身型破傷風を疑い,入院当日に破傷風免疫グロブリンを投与した.投与後症状は改善傾向となり,入院第7病日には飲水可能となった.徐々に食事も摂取でき,開口制限もなくなり,退院した

    researchmap

  • Two Cases of Generalized Tetanus Presenting with Dysphagia as an Initial Symptom

    55 ( 11 )   973 - 976   2003.11

     More details

  • 多系統萎縮症と自律神経障害 多系統萎縮症における突然死の病態の解明,及び治療法の確立を目指して

    下畑 享良, 金澤 雅人, 寺島 健史, 小野寺 理, 西澤 正豊, 中山 秀章, 篠田 秀夫

    日本自律神経学会総会プログラム・抄録集   56回   64 - 64   2003.10

     More details

    Language:Japanese   Publisher:日本自律神経学会  

    researchmap

  • 低アルブミン血症と眼球運動失行を伴う脊髄小脳変性症(EAOH)の原因遺伝子アプラタキンの一本鎖DNA修復機能における役割に関する検討(Aprataxin, the causative gene for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) as a member of ssDNA repair machinery.: Implication of impaired DNA repair systems

    伊達 英俊, 五十嵐 修一, 高橋 俊昭, 高野 弘基, 小野寺 理, 西澤 正豊, 佐野 泰照, 辻 省次

    神経化学   42 ( 2-3 )   264 - 264   2003.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • 全長DRPLA蛋白はCREB及びp53転写活性化を抑制する(Full-length DRPLA proteins suppress CREB- and p53- dependent transcriptional activation)

    下畑 享良, 小倉 香織, 成瀬 聡, 五十嵐 修一, 佐藤 俊哉, 小野寺 理, 西澤 正豊, 辻 省次

    神経化学   42 ( 2-3 )   265 - 265   2003.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • ポリグルタミン病における転写障害assay系の確立(Establishment of functional assays system for polyglutamine disease.)

    高橋 俊昭, 野崎 兼吉, 小野寺 理, 西澤 正豊, 辻 省次

    神経化学   42 ( 2-3 )   278 - 278   2003.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • 1本鎖DNA修復におけるアプラタキシンの生化学的機能の解析(Analyses of biochemical functions of aprataxin in DNA single-strand break repair)

    高橋 哲哉, 五十嵐 修一, 伊達 英俊, 小野寺 理, 西澤 正豊, 辻 省次

    神経化学   42 ( 2-3 )   279 - 279   2003.8

     More details

    Language:English   Publisher:日本神経化学会  

    researchmap

  • ステロイドパルス療法が著効したCMV感染に伴うIgM抗GM2抗体陽性Guillain-Barre症候群の1例

    他田 正義, 小野寺 理, 河内 泉, 原 賢寿, 佐藤 正久, 吉野 英, 浅野 敦子, 相馬 芳明, 辻 省次

    脳と神経   55 ( 7 )   615 - 621   2003.7

     More details

    Language:Japanese   Publisher:(株)医学書院  

    27歳男.四肢の痺れ感,脱力を主訴とした.38度台の発熱の5日後から主訴を自覚し,その後嚥下困難感も出現した.Cytomegalovirus(CMV)感染に伴うIgM抗G M2抗体陽性のギラン・バレー症候群(GRS)の重症例で,初期には二重濾過法によるプラズマフェレーシスが効果的であったが,その後治療抵抗性で症状は増悪し,呼吸不全,球麻痺,臥床状態となった.持続性のCMV感染症を疑い,ganciclovirの点滴を開始したが,効果は十分でなかった.発症2ヵ月後からステロイドパルス療法を施行し,劇的な改善が得られた.計7コースのパルス療法で,独歩可能となった.入院時上昇していた血清IgM抗CMV抗体の推移は病勢に一致しており,抗体価の推移からCMV感染症と診断した

    researchmap

  • Steroid-pulse Therapy in Guillain-Barre Syndrome Associated with Cytomegalovirus Infection : A Case Report

    55 ( 7 )   615 - 621   2003.7

     More details

  • 遺伝性ニューロパチーの診断システムの確立及び治療に関する研究 EAOH(眼球運動失行と低アルブミン血症を伴う早発型失調症)の臨床症状の検討(第2報) 経過と類縁疾患との比較

    小野寺 理, 横関 明男, 伊達 英俊, 佐野 泰照, 五十嵐 修一, 辻 省次

    厚生労働省精神・神経疾患研究委託費研究報告集   平成14年度   163 - 163   2003.6

     More details

    Language:Japanese   Publisher:国立精神・神経センター  

    researchmap

  • 【内科キーワード2003】 神経・筋 背髄小脳変性症の分類とわが国での頻度

    小野寺 理

    内科   91 ( 6 )   1323 - 1324   2003.6

     More details

    Language:Japanese   Publisher:(株)南江堂  

    researchmap

  • 【内科キーワード2003】 神経・筋 ポリグルタミン病の新展開

    小野寺 理

    内科   91 ( 6 )   1325 - 1325   2003.6

     More details

    Language:Japanese   Publisher:(株)南江堂  

    researchmap

  • SCA-17 : homozygoteの1剖検例

    豊島 靖子, 山田 光則, 小野寺 理, 稲永 親憲, 森田 昌宏, 辻 省次, 高橋 均

    Neuropathology : official journal the Japanese Society of Neuropathology   23   121 - 121   2003.5

     More details

  • 【遺伝子診断と画像診断】 神経領域における遺伝子診断の現状 脊髄小脳変性症(SCA3,SCA6)を中心に

    小野寺 理

    臨床放射線   48 ( 4 )   455 - 463   2003.4

     More details

    Language:Japanese   Publisher:金原出版(株)  

    researchmap

  • ポリグルタミン病における神経変性の分子病態機序と治療法開発への展望

    辻 省次, 佐藤 俊哉, 下畑 光輝, 下畑 享良, 五十嵐 修一, 成瀬 聡, 小野寺 理

    日本医師会雑誌   129 ( 6 )   785 - 787   2003.3

     More details

    Language:Japanese   Publisher:日本医師会  

    researchmap

  • DRPLA蛋白発現によるPML小体の分布変化

    下畑 享良, 山田 光則, 下畑 光輝, 佐藤 俊哉, 佐藤 晶, 小野寺 理, 成瀬 聡, 高橋 均, 辻 省次

    臨床神経学   42 ( 12 )   1281 - 1281   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 眼球運動失行,低アルブミン血症を伴う早期発症型失調症の原因蛋白aprataxinの解析

    佐野 泰照, 森松 光紀, 五十嵐 修一, 小野寺 理, 辻 省次

    山口医学   51 ( 6 )   208 - 209   2002.12

     More details

    Language:Japanese   Publisher:山口大学医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2003181739

  • Diffuse lewy body disease(DLBD)患者におけるsynuclein familyの遺伝子配列の解析

    大竹 弘哲, 小野寺 理, 五十嵐 修一, 斎藤 正明, 辻 省次, 高橋 均, 石川 厚, 出塚 次郎, 若林 允甫

    臨床神経学   42 ( 12 )   1281 - 1281   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 眼球運動失行,低アルブミン血症を伴う早発型失調症の原因蛋白aprataxinの解析

    佐野 泰照, 伊達 英俊, 五十嵐 修一, 小野寺 理, 小宅 睦郎, 辻 省次, 高橋 均, 福原 信義, 巻淵 隆夫, 森松 光紀

    臨床神経学   42 ( 12 )   1215 - 1215   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経内科疾患でステロイド治療は特発性大腿骨頭壊死(IONF)の危険因子となるか

    菊池 泰子, 小野寺 理, 辻 省次

    臨床神経学   42 ( 12 )   1246 - 1246   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 眼球運動失行(OMA)を伴う早発型失調症(EAOH) アプラタキシン変異とOMAの関連

    横関 明男, 伊達 英俊, 小林 央, 小野寺 理, 辻 省次, 岩淵 潔, 長友 秀樹, 出塚 次郎, 若林 允甫

    臨床神経学   42 ( 12 )   1215 - 1215   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 高オルニチン血症高アンモニア血症ホモシトルリン尿症(HHH)の遺伝子変異の検討

    後藤 公文, 小野寺 理, 伊達 英俊, 大竹 弘哲, 小宅 睦朗, 小池 亮子, 辻 省次, 加藤 繁夫

    臨床神経学   42 ( 12 )   1373 - 1373   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 磁気共鳴神経路画像の神経疾患への応用

    寺島 健史, 松澤 等, 小野寺 理, 辻 省次, 中田 力

    臨床神経学   42 ( 12 )   1332 - 1332   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • CO中毒におけるMRI拡散強調画像の有用性について 当科5症例の検討

    高橋 俊昭, 寺島 健史, 下畑 享良, 飯塚 統, 小宅 睦郎, 小野寺 理, 成瀬 聡, 辻 省次, 三瓶 一弘

    臨床神経学   42 ( 12 )   1408 - 1408   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 当科Churg-Strauss症候群(CSS)14例の臨床像の検討

    新保 淳輔, 小野寺 理, 田中 恵子, 辻 省次, 宮崎 滋, 田中 正美, 青木 賢樹, 藤田 信也, 田部 浩行

    臨床神経学   42 ( 12 )   1285 - 1285   2002.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Synuclein gene alternation in a case of dementia with Lewy bodies (DLB)

    H Ohtake, O Onodera, S Igarashi, M Saito, H Takahashi, A Ishikawa, J Idezuka, M Wakabayashi, B Giasson, VMY Lee, JQ Trojanowski, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   71 ( 4 )   518 - 518   2002.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • 繰り返す血管造影で検出しえなかった潜在性脊髄硬膜動静脈瘻の一例

    金澤 雅人, 堅田 慎一, 小野寺 理, 田中 恵子, 辻 省次

    臨床神経学   42 ( 10 )   990 - 990   2002.10

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【ポリグルタミン病の病態機序】 異常蛋白処理機構とポリグルタミン病

    小野寺 理

    神経研究の進歩   46 ( 5 )   669 - 679   2002.10

     More details

    Language:Japanese   Publisher:(株)医学書院  

    ポリグルタミン病の病態機序を考える上で,長さ依存性,閾値の存在,時間依存性という特徴が挙げられる.この現象を説明する機序として,ある確率に基づく蛋白質の構造異性体への変化が疑われる.本症の病態に対して,蛋白面からのアプローチの一方で,そのような不要蛋白に対する細胞の処理機構からの検討が始められている.その一つにaggresomeがある.AggresomeはMTOC(微小管形成中心)に形成され,microtubules上をMTOCに向け移動し,intermediate filaments;IFsと結合している.結果としてIFsの正常な構造は失われる.本症の病態について,ポリグルタミン鎖の病原性獲得機序の面と,細胞内の,その処理機構の面からの解析が必要と考える

    DOI: 10.11477/mf.1431901390

    researchmap

  • 【常染色体劣性遺伝性脊髄小脳変性症】 眼球運動失行と低アルブミン血症を伴う早発型脊髄小脳失調症の分子遺伝学

    伊達 英俊, 小野寺 理, 辻 省次

    神経内科   57 ( 2 )   113 - 118   2002.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【常染色体劣性遺伝性脊髄小脳変性症】 眼球運動失行と低アルブミン血症を伴う早発型脊髄小脳失調症の臨床

    横関 明男, 伊達 英俊, 小野寺 理

    神経内科   57 ( 2 )   108 - 112   2002.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【常染色体劣性遺伝性脊髄小脳変性症】 Friedreich失調症と常染色体劣性遺伝性脊髄小脳変性症

    小野寺 理, 辻 省次

    神経内科   57 ( 2 )   99 - 107   2002.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 血管病変との鑑別に苦慮し1H-MRSが診断に有効であった多発性硬化症の一例

    堅田 慎一, 寺島 健史, 小野寺 理, 田中 恵子, 辻 省次

    臨床神経学   42 ( 7 )   654 - 654   2002.7

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【精神・神経疾患とゲノム】 常染色体劣性遺伝性脊髄小脳変性症(アプラタキシン欠損症)

    伊達 英俊, 小野寺 理, 辻 省次

    ゲノム医学   2 ( 3 )   241 - 250   2002.6

     More details

    Language:Japanese   Publisher:(株)メディカルレビュー社  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2002249716

  • Spinocerebellar ataxia type 6(SCA6)遺伝子変異を合併したオリーブ橋小脳萎縮症の1例

    細山 香織, 下畑 享良, 平石 哲也, 小野寺 理, 辻 省次

    神経内科   56 ( 1 )   63 - 66   2002.1

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    48歳女.歩行時のふらつきと呂律が回らないことを主訴とした.頭部MRIで小脳・橋の萎縮とT2強調水平断像での橋横走線維の高信号化(いわゆる十字サイン)を認めたため標記萎縮症と診断した.その後の遺伝子診断でCACNA1A遺伝子におけるCAGリピートの伸長(SCA6遺伝子変異)を認めた

    researchmap

  • 変性疾患 副腎白質ジストロフィー(adrenoleukodystrophy:ALD) 治療法研究の進歩

    小野寺 理, 辻 省次

    Annual Review神経   2002   197 - 208   2002.1

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • Early-onset ataxia associated with ocular motor apraxia and hypoalbuminemia (EAOH), a variant form of Friedreich's ataxia. Clinical and genetic analyses

    O Onodera, H Date, A Yokoseki, S Igarashi, H Tanaka, S Tsuji

    MOVEMENT DISORDERS   17   S312 - S313   2002

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 多発性硬化症に伴う三叉神経障害のMRI像,臨床像の検討

    和泉 大輔, 小野寺 理, 辻 省次

    臨床神経学   41 ( 11 )   868 - 868   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 【21世紀の神経免疫学 展望】 ロイコトリエン受容体拮抗薬とChurg-Strauss症候群

    新保 淳輔, 小野寺 理

    医学のあゆみ   別冊 ( 21世紀の神経免疫学-展望 )   190 - 194   2001.11

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    researchmap

  • 【成人にみられる代謝性神経疾患】 成人にみられる主な代謝性神経疾患 副腎白質ジストロフィー

    田中 惠子, 小野寺 理

    Clinical Neuroscience   19 ( 12 )   1383 - 1385   2001.11

     More details

    Language:Japanese   Publisher:(株)中外医学社  

    researchmap

  • 副腎白質ジストロフィー症(ALD)に対する非血縁者間骨髄移植の経験

    斉藤 浩史, 姉崎 利治, 小野寺 理, 辻 省次, 矢部 普正

    神経治療学   18 ( 5〜6 )   512 - 512   2001.11

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 伸長ポリグルタミン鎖による細胞障害に対するCREB転写活性化の効果

    下畑 享良, 成瀬 聡, 小野寺 理, 下畑 光輝, 辻 省次

    臨床神経学   41 ( 11 )   836 - 836   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ALD/AMNの自然歴に関する検討 当科経験11例の検討

    高橋 俊昭, 斎藤 浩史, 高野 弘基, 小野寺 理, 辻 省次, 小池 亮子, 中島 孝, 石川 厚

    臨床神経学   41 ( 11 )   1006 - 1006   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • DRPLA遺伝子36〜48 CAGリピートは発症と関連するか?

    野崎 兼吉, 小野寺 理, 小出 隆司, 辻 省次, 小国 弘量, 斎藤 加代子, 山本 光利

    臨床神経学   41 ( 11 )   900 - 900   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 第9染色体短腕に連鎖する低アルブミン血症を伴う早発型脊髄小脳変性症(EOAHA)の臨床像の検討

    横関 明男, 伊達 英俊, 下畑 享良, 小野寺 理, 小林 央, 辻 省次, 田中 一, 小池 亮子, 湯浅 龍彦, 植川 和利

    臨床神経学   41 ( 11 )   836 - 836   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 3テスラ超高磁場磁気共鳴画像によるラムダチャート解析 神経変性疾患への応用

    寺島 健史, 松澤 等, 小野寺 理, 辻 省次, 中田 力

    臨床神経学   41 ( 11 )   942 - 942   2001.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PCR検出定量システムを利用したSNPs解析〜ABI PRISM 7700の使用経験から

    大竹 弘哲, 小野寺 理, 辻 省次

    新潟医学会雑誌   115 ( 10 )   546 - 546   2001.10

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2002189728

  • 【遺伝子診断 最近の展開】 遺伝子診断の臨床トピックス 脊髄小脳変性症の遺伝子診断

    原 賢寿, 小野寺 理, 辻 省次

    小児科診療   64 ( 10 )   1505 - 1511   2001.10

     More details

    Language:Japanese   Publisher:(株)診断と治療社  

    脊髄小脳変性症とは運動失調を主症状とする原因不明の神経変性疾患の総称であるが,かつては原因不明とされた神経難病もその原因遺伝子が続々と発見されてきている.小児科領域において遭遇する可能性のある遺伝性失調症としては,Friedreich失調症及びその類縁疾患,歯状核赤核淡蒼球ルイ体萎縮症,脊髄小脳失調症,発作性失調症,毛細管拡張性運動失調などがあげられる

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2002085539

  • 眼球運動失行と低アルブミン血症を伴う早発型失調症(EAOH)の疾患遺伝子の同定

    伊達 英俊, 小野寺 理, 五十嵐 修一, 河内 泉, 田中 一, 小池 亮子, 辻 省次, 湯浅 龍彦, 植川 和利, 福原 信義

    新潟医学会雑誌   115 ( 10 )   543 - 544   2001.10

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2002202411

  • Early-onset ataxia with ocular motor apraxia and hypoalbuminemia, a variant form of Friedreich's ataxia, is caused by mutations in a novel HIT superfamily protein, aprataxin.

    H Date, O Onodera, S Igarashi, A Yokoseki, H Tanaka, R Koike, S Tsuji, K Iwabuchi, H Nagatomo, Y Sekijima, T Hiroi, K Uekawa, E Uyama, T Yuasa, Y Awaya, K Saitou, T Sakai, S Sugano

    AMERICAN JOURNAL OF HUMAN GENETICS   69 ( 4 )   196 - 196   2001.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • 皮膚筋炎に合併した筋及び多発皮下型サルコイドーシスの1例

    後藤 一美, 富山 勝博, 浅田 一幸, 田村 正和, 野本 真由美, 高田 俊範, 小野寺 理

    日本皮膚科学会雑誌   111 ( 10 )   1519 - 1519   2001.9

     More details

    Language:Japanese   Publisher:(公社)日本皮膚科学会  

    researchmap

  • 目でみるバイオサイエンス ポリグルタミン病とaggresome

    小野寺 理, 野崎 兼吉, 下畑 享良

    内科   88 ( 3 )   569 - 571   2001.9

     More details

    Language:Japanese   Publisher:(株)南江堂  

    researchmap

  • Early-onset ataxia associated with ocular motor apraxia and hypoalbuminemia, a variant form of Friedreich's ataxia: Clinical and genetic analyses of 20 Japanese families

    A Yokoseki, H Date, O Onodera, S Igarashi, H Tanaka, R Koike, S Tsuji, K Iwabuchi, H Nagatomo, Y Sekijima, S Ikeda, T Hiroi, K Uckawa, E Uyama, A Ishigaki, T Yuasa, Y Awaya, K Saitou, T Sakai, Y Takahashi, M Hayashi

    ANNALS OF NEUROLOGY   50 ( 3 )   S9 - S10   2001.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-LISS  

    Web of Science

    researchmap

  • 10代にて発症した"低アルブミン血症と眼球運動失行を伴う早発型運動失調症(EAOH)"の1例

    横関 明男, 伊達 英俊, 小野寺 理, 小林 央, 辻 省次

    臨床神経学   41 ( 6 )   339 - 339   2001.6

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン鎖の凝集体形成における周辺アミノ酸配列の影響に関する検討

    野崎 兼吉, 小野寺 理, 辻 省次

    新潟県医師会報   ( 614 )   6 - 6   2001.5

     More details

    Language:Japanese   Publisher:新潟県医師会  

    researchmap

  • 脊髄小脳変性症の遺伝子異常と臨床像 CAGリピート病を中心に

    野崎 兼吉, 小野寺 理, 高野 弘基, 辻 省次

    新潟県医師会報   ( 614 )   2 - 5   2001.5

     More details

    Language:Japanese   Publisher:新潟県医師会  

    researchmap

  • 遺伝子性ニューロパチーの成因及び治療に関する研究

    祖父江 元, 秋口 一郎, 早坂 清, 中川 正法, 佐古田 三郎, 松村 喜一郎, 小野寺 理, 池田 修一, 山村 隆, 安東 由紀雄, 馬場 正之, 中里 雅光, 安田 斎, 斎藤 豊和, 池中 一裕, 吉良 潤一, 和田 圭司, 中島 健二, 渡部 和彦, 岡 伸幸, 安東 えい子

    厚生省精神・神経疾患研究委託費総括研究報告書 遺伝子性ニューロパチーの成因及び治療に関する研究   平成10〜12年度   1 - 10   2001.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    researchmap

  • Charcot-Marie-Tooth病type 2Aと新たなCMT類似疾患の分子遺伝学的解析

    斎藤 正明, 伊達 英俊, 佐藤 正久, 小野寺 理, 田中 恵子, 辻 省次

    厚生省精神・神経疾患研究委託費総括研究報告書 遺伝子性ニューロパチーの成因及び治療に関する研究   平成10〜12年度   54 - 54   2001.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    CMTタイプ2について,その臨床遺伝学的特徴を明らかにすると共に,多型解析・ハプロタイプ解析・連鎖解析・変異遺伝子解析等の分子遺伝学的アプローチによる原因遺伝子座・原因遺伝子の解明を試みた.CMT2Aの2家系を本邦ではじめて見い出した,臨床遺伝学的特徴は下腿前方筋群と同様に後方筋群も障害される.深部反射は減弱するものの,全消失は稀で,末梢神経の肥厚は稀,感覚障害はあっても稀という点であった.これら2家系における原因遺伝子が同領域に連鎖することを確認し,分子遺伝学的にCMT2Aと診断した.次に同一家系内にパーキソニズムとCMT類似の臨床症状を認める1家系の遺伝子学的特徴を明らかにし,既知の疾患との分子遺伝学的な異同について検討した.その結果,本家系はいずれの疾患とも分子遺伝学的に異なっており,独立した一つの疾患単位である可能性が高いものと考えた

    researchmap

  • パーキンソニズムとCharcot-Marie-Tooth病類似の下肢筋萎縮を呈した1家系 UCH-L1遺伝子近傍のマーカーを用いた候補遺伝子アプローチ

    斎藤 正明, 伊達 英俊, 佐藤 正久, 小野寺 理, 辻 省次

    厚生省精神・神経疾患研究委託費総括研究報告書 遺伝子性ニューロパチーの成因及び治療に関する研究   平成10〜12年度   31 - 31   2001.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    パーキンソニズムとCharcot-Marie-Tooth病類似の下肢筋萎縮を呈した1家系を経験した.本症の既知の疾患との分子遺伝学的相違を示すと共に,本家系が独立した疾患単位である可能性を報告した.ヒトではUCH-L1遺伝子変異によって発症する常染色体優性遺伝性パーキンソン病の1家系がドイツから報告されており,UCH-L1遺伝子は本疾患の候補遺伝子となり得ると考え,UCH-L1遺伝子近傍の11個のマイクロサテライトマーカーを用いたハプロタイプ解析を行い,UCH-L1遺伝子を含む4番染色体短腕4p14領域についての連鎖解析を行った.その結果,本科系においては,UCH-L1遺伝子近傍において少なくとも3種類のハプロタイプが存在する可能性が高いものと想定されたが,発症者とその同胞である非発症者において共通するハプロタイプが想定された

    researchmap

  • 脳梗塞再発直後からHigh intensity Transient Signals(HITS)を経時的に観察した抗リン脂質抗体症候群の1例

    山岡 由美子, 菅原 和子, 佐藤 晶, 小野寺 理, 辻 省次, 榛沢 和彦

    Neurosonology   14 ( 1 )   25 - 29   2001.2

     More details

    Language:Japanese   Publisher:(一社)日本脳神経超音波学会  

    38歳女.全身性エリテマトーデス類似状態に抗リン脂質抗体症候群を続発した症例を経験した.HITS(High intensity Transient Signals)を,脳梗塞急性期から慢性期まで経時的に観察した結果,急性期にはHITSの総量のみならず,大きな音エネルギーを持つ栓子の割合が増加していた.また,大きさや固さをを増した栓子が多数出現していた可能性も認められた

    DOI: 10.2301/neurosonology.14.25

    CiNii Article

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2001206491

  • 副腎白質ジストロフィー

    田中惠子, 小野寺 理

    Clinical Neuroscience   19(12)   1383(57)-1385(59)   2001

     More details

  • 増大ポリグルタミン鎖の核移行に伴う細胞障害機序

    下畑 享良, 小野寺 理, 佐藤 晶, 佐藤 俊哉, 成瀬 聡, 辻 省次, 山田 光則, 高橋 均

    臨床神経学   40 ( 12 )   1318 - 1318   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 遺伝子性ニューロパチーの成因および治療に関する研究 パーキンソニズムとCharcot-Marie-Tooth病類似の下肢筋萎縮を呈した1家系 その臨床像および分子遺伝学的解析を中心として

    斎藤 正明, 佐藤 正久, 小野寺 理, 田中 恵子, 辻 省次

    厚生省精神・神経疾患研究委託費による研究報告集   平成11年度   115 - 115   2000.12

     More details

    Language:Japanese   Publisher:国立精神・神経センター  

    パーキンソニズムとCMT類似の下肢筋萎縮を呈する1家系を報告した.パーキンソン症状は特発性パーキンソン病に類似し,l-dopaに対する反応も良好であった.本例の末梢神経障害は軸索障害が主体であるが,CMT type2における既知のローカスとの連鎖は否定的であった

    researchmap

  • 透析が誘因と考えられたWernicke脳症

    西川 順治, 飯塚 統, 他田 正義, 小野寺 理, 原 賢樹, 相馬 芳明, 辻 省次, 田沼 厚人, 後藤 眞, 橋本 哲

    新潟医学会雑誌   114 ( 12 )   479 - 479   2000.12

  • 蛍光ビデオ顕微鏡による歯状核赤核淡蒼球ルイ体萎縮症(DRPLA)のポリグルタミン凝集の観察

    豊島 至, 菅原 正伯, 和田 千鶴, 阿部 エリカ, 渡辺 純夫, 下畑 享良, 小出 玲爾, 小野寺 理, 辻 省次

    臨床神経学   40 ( 12 )   1319 - 1319   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • PranlukastはChurg-Strauss Syndrome(CSS)の誘因となるか

    新保 淳輔, 小野寺 理, 原 賢樹, 田中 恵子, 辻 省次

    臨床神経学   40 ( 12 )   1475 - 1475   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 細胞体内でのmiss-folding proteinの共通処理機構としてのAggresomeの役割 ポリグルタミン病との関連

    小野寺 理, 下畑 享良, 野崎 謙吉, 辻 省次, 永井 義隆, Strittmatter Warren J

    臨床神経学   40 ( 12 )   1318 - 1318   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • ポリグルタミン鎖の凝集体形成における周辺アミノ酸配列の影響に関する検討

    野崎 兼吉, 小野寺 理, 辻 省次

    臨床神経学   40 ( 12 )   1343 - 1343   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • MJD/SCA3のMRI変化に対するCAGリピートと年齢の影響

    他田 正義, 小野寺 理, 辻 省次

    臨床神経学   40 ( 12 )   1406 - 1406   2000.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Expanded polyglutamine stretches associated with CAG repeat diseases interact with TAF(II)130, interfering with CREB-dependent transcription.

    T Shimohata, T Nakajima, M Yamada, C Uchida, O Onodera, S Naruse, T Sato, T Kimura, K Nozaki, Y Sano, A Sato, M Oyake, N Tanese, H Takahashi, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   67 ( 4 )   375 - 375   2000.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:CELL PRESS  

    Web of Science

    researchmap

  • 伸張ポリグルタミン鎖はTATA結合蛋白髄伴因子(TAF130)との結合を介し,CREB転写活性化を阻害する

    下畑 享良, 中島 利博, 山田 光則, 内田 千晴, 小野寺 理, 成瀬 聡, 佐藤 俊哉, 木村 哲也, 野崎 兼吉, 小宅 睦郎

    神経化学   39 ( 3 )   301 - 301   2000.10

     More details

    Language:Japanese   Publisher:日本神経化学会  

    researchmap

  • 非ヘルペス性急性脳炎の臨床経過と治療および予後について

    新井 亜希, 西川 順治, 他田 正義, 小野寺 理, 下畑 光輝, 原 賢寿, 相馬 芳明, 辻 省次

    神経治療学   17 ( 5 )   454 - 454   2000.9

     More details

    Language:Japanese   Publisher:日本神経治療学会  

    researchmap

  • 【眼で見る神経内科】 多発性の嚢胞と石灰化を認めた転移性脳腫瘍

    志知 隆雄, 小野寺 理, 佐藤 晶, 加藤 佳子, 辻 省次

    神経内科   53 ( Suppl.2 )   430 - 431   2000.9

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    researchmap

  • 【遺伝性脊髄小脳変性症の地域特異性】 信越・北陸地方における遺伝性脊髄小脳変性症の特異性

    下畑 光輝, 小野寺 理, 辻 省次

    神経内科   53 ( 2 )   111 - 115   2000.8

     More details

    Language:Japanese   Publisher:(有)科学評論社  

    1993年4月から2000年5月迄の間に遺伝子診断の依頼を受けたもののうち,依頼施設が新潟県,秋田県,山形県庄内地区,福島県会津地区,富山県であった168家系について診断結果を解析した.優性遺伝形式をとる脊髄小脳変性症と判断された157家系の解析結果では,MJD/SCA3が63家系(43%)に認められ,ついでSCA6が39家系(27%),DRPLAが11家系(8%)であった.また当初孤発例と考えられたが,遺伝子診断で診断が確定した症例を含めた168家系の結果では,やはりMJD/SCA3が最多であったが,SCA6,DRPLAの割合が増加していた.これらの結果から,信越・北陸地方での特徴としてDRPLAの頻度が高いこと,またSCA6の頻度が高く,SCA1の頻度が極端に少ないことがあげられた

    researchmap

  • ステロイドパルス療法が著効したCMV感染に伴う抗GM2抗体陽性Guillain-Barre症候群の1例

    他田 正義, 小野寺 理, 佐藤 正久, 相馬 芳明, 辻 省次, 吉野 英, 浅野 敦子

    臨床神経学   40 ( 3 )   277 - 277   2000.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • MRIにて脳幹部に著明な腫脹と造影効果を認め硬膜動静脈瘻が疑われた1例

    他田 正義, 志知 隆雄, 小野寺 理, 相馬 芳明, 辻 省次

    臨床神経学   40 ( 2 )   195 - 195   2000.2

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Multiple system atrophy剖検脳におけるα-synuclein遺伝子の全コード領域の解析

    小澤 鉄太郎, 高野 弘基, 小野寺 理, 小林 央, 池内 健, 小出 玲爾, 奥泉 薫, 下畑 享良, 辻 省次, 若林 孝一

    臨床神経学   39 ( 12 )   1336 - 1336   1999.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 歯状核赤核淡蒼球ルイ体萎縮症(DRPLA) 増大ポリグルタミン鎖に結合する細胞内蛋白質の検索

    下畑 享良, 小野寺 理, 小出 玲爾, 佐藤 晶, 野崎 兼吉, 辻 省次, 山田 光則, 高橋 均

    臨床神経学   39 ( 12 )   1426 - 1426   1999.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • SCA6は他のポリグルタミン病と同一の疾患か? MRIからの検討

    小野寺 理, 池内 健, 五十嵐 修一, 辻 省次

    臨床神経学   39 ( 12 )   1427 - 1427   1999.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 増大したポリグルタミン鎖の凝集体形成能は周辺のアミノ酸配列によって影響を受ける

    野崎 兼吉, 小野寺 理, 三瓶 一弘, 下畑 享良, 辻 省次

    臨床神経学   39 ( 12 )   1394 - 1394   1999.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Amino acids flanking polyglutamine stretches influence the competence of aggregate formation.

    K Nozaki, O Onodera, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   65 ( 4 )   A464 - A464   1999.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • CACNA1A遺伝子変異に基づく神経疾患の分子遺伝学

    辻 省次, 五十嵐 修一, 高橋 哲哉, 志知 隆雄, 小野寺 理

    神経化学   38 ( 3 )   213 - 213   1999.9

     More details

    Language:Japanese   Publisher:日本神経化学会  

    researchmap

  • DRPLAにおける神経細胞死

    下畑 享良, 山田 光則, 五十嵐 修一, 小野寺 理, 小出 玲爾, 佐藤 晶, 佐藤 駿哉, 野崎 兼吉, 高橋 均, 辻 省次

    神経化学   38 ( 3 )   204 - 204   1999.9

     More details

    Language:Japanese   Publisher:日本神経化学会  

    researchmap

  • ポリグルタミン凝集の時間経過と細胞死

    豊島 至, 菅原 正伯, 加藤 一麿, 和田 千鶴, 下畑 享良, 小出 玲爾, 小野寺 理, 辻 省次

    神経化学   38 ( 3 )   222 - 222   1999.9

     More details

    Language:Japanese   Publisher:日本神経化学会  

    researchmap

  • 数日間に渡る発作性の失調症状を示し,アセタゾラミドが奏効した周期性失調症と考えられる1例

    志知 隆雄, 小野寺 理, 磯田 昌岐, 相馬 芳明, 辻 省次

    臨床神経学   39 ( 8 )   890 - 890   1999.8

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • 神経難病の分子機構 タンパク質コンフォメーション異常の視点から 増大したポリグルタミン鎖の凝集体形成能と中間径フィラメント(IF)との関係

    小野寺 理, 野崎 兼吉, 辻 省次, 永井 義隆, Burke James R, Strittmatter Warren J

    生化学   71 ( 8 )   639 - 639   1999.8

     More details

    Language:Japanese   Publisher:(公社)日本生化学会  

    researchmap

  • トランスグルタミナーゼによるタンパク質架橋反応の多様性 発生から病態まで ポリグルタミン病の発症機構

    辻 省次, 下畑 享良, 小野寺 理

    生化学   71 ( 8 )   659 - 659   1999.8

     More details

    Language:Japanese   Publisher:(公社)日本生化学会  

    researchmap

  • 脳梗塞を呈し,High Intensity Transient Signals(HITS)を検出した抗リン脂質抗体症候群(APS)の1例

    山岡 由美子, 菅原 和子, 佐藤 晶, 小野寺 理, 辻 省次, 榛沢 和彦

    Neurosonology   12 ( Suppl. )   65 - 65   1999.4

     More details

    Language:Japanese   Publisher:(一社)日本脳神経超音波学会  

    researchmap

  • 5)脳梗塞を合併したantiphospholipid陽性の若年女性で経学道心エコー検査で大動脈弁に非細菌性疣贅を認め経頭蓋超音波検査により High Intensity Transient Signals(HITS)が多数検出された症例(I. 一般演題, 第218回新潟循環器談話会例会)

    113 ( 4 )   233 - 234   1999.4

  • 増大したポリグルタミン鎖は凝集し中間径フィラメント(IF)の構築を破壊する

    小野寺 理, 辻 省次, Burke James R, Miller Sara E, Hester Susan, Roses Allen D, Strittmatter Warren J

    臨床神経学   39 ( 1 )   123 - 123   1999.1

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Bruton型無ガンマグロブリン血症に合併した慢性エンテロウイルス髄膜炎と水頭症の1例

    小澤 鉄太郎, 小野寺 理, 飯塚 統

    脳と神経   50 ( 2 )   191 - 196   1998.2

     More details

    Language:Japanese   Publisher:(株)医学書院  

    1歳時より100mg/kgのガンマグロブリン(γ-gl)を月1回静注されていたBruton型無γ-gl血症の患者が,慢性エンテロウイルス髄膜炎のため,10歳時に水頭症を発症し当科に入院した.入院後は脳室ドレナージを行い,400mg/kgのγ-glを月1回静注しながら,125〜250mgのγ-glを週1回(8週間で総投与量1.5g)脳室内に投与したところ髄膜炎症状は改善した

    researchmap

  • 不顕性に経過したprevertebral abscess 急性化膿性髄膜炎と敗血症性ショックをきたした1剖検例

    小澤 鉄太郎, 小野寺 理, 柿田 明美

    脳と神経   50 ( 1 )   75 - 79   1998.1

     More details

    Language:Japanese   Publisher:(株)医学書院  

    約3ヵ月間にわたり軽い後頸部痛のみを訴えていた66歳男が急激な黄色ブドウ球菌髄膜炎を発症し,その第2病日に敗血症性ショックで死亡した.剖検にて,頸椎,胸椎椎体腹側の結合織性被膜に覆われたprevertebral abscessと,これと連続する化膿性椎体・椎間板炎が広範に認められた.膿瘍の器質化の程度から,化膿巣はまず上位頸椎腹側に形成され,その後椎体腹側を上下に走るprevertebral spaceに沿って尾側に進展したものと考えられた.更に化膿巣は隣接する椎体・椎間板へと波及し,ついには敗血症から化膿性髄膜炎に至ったものと考えられた

    researchmap

  • Lack of association of very low density lipoprotein (VLDL) receptor gene polymorphism with Caucasian Alzheimer's disease.

    K Okuizumi, O Onodera, K Seki, H Tanaka, Y Namba, K Ikeda, AM Saunders, MA Pericak-Vance, AD Roses, S Tsuji

    AMERICAN JOURNAL OF HUMAN GENETICS   61 ( 4 )   A289 - A289   1997.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • Poly Q domains are substrates of transglutaminase: Implications for expanded CAG/poly Q repeat disorders

    AJL Cooper, KFR Sheu, Burke, JR, O Onodera, WJ Strittmatter, AD Roses, JP Blass

    JOURNAL OF NEUROCHEMISTRY   69   S267 - S267   1997

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT-RAVEN PUBL  

    Web of Science

    researchmap

  • Pick病脳におけるapolipoprotein Eの免疫組織化学的検討

    林 森太郎, 若林 孝一, 岩永 圭介, 柿田 明美, 関 耕治, 田中 政春, 奥泉 薫, 小野寺 理, 田中 一, 辻 省次, 高橋 均

    Neuropathology : official journal the Japanese Society of Neuropathology   16   241 - 241   1996.5

     More details

  • 6) 精神分裂病の分子遺伝学的研究(I. 一般演題, 平成7年度新潟大学医学部精神医学教室同窓会集談会)

    田中 敏恒, 福島 昇, 高橋 誠, 亀田 謙介, 飯田 眞, 五十嵐 修一, 三瓶 一弘, 田中 一, 辻 省次, 小野寺 理, 高橋 邦明, 小林 慎一

    新潟医学会雑誌   110 ( 4 )   156 - 157   1996.4

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • Non-Mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph disease

    T Ikeuchi, S Igarashi, Y Takiyama, O Onodera, M Oyake, H Takano, R Koide, H Tanaka, S Tsuji

    NEUROLOGY   46 ( 2 )   30005 - 30005   1996.2

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LITTLE BROWN CO  

    Web of Science

    researchmap

  • An association study between schizophrenia and dopamine D3 receptorgene polymorphism

    Toshihisa TANAKA, Shuichi IGARASHI, Osamu ONODERA

    Annual report, Brain Research Institute, Niigata University   29   128 - 128   1996

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • Lack of association between dopamine D2 receptor gene Cys311 variantand schizophrenia

    Toshihisa TANAKA, Shuichi IGARASHI, Osamu ONODERA

    Annual report, Brain Research Institute, Niigata University   29   129 - 129   1996

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • Somatic mosaicism of expanded CAG repeats in brains of patients withdentatorubral-pallidoluysian atrophy (DRPLA): Cellular population-dependent dynamics of mitotic instability

    Hiroki TAKANO, Osamu ONODERA, hitoshi TAKAHASHI

    Annual report, Brain Research Institute, Niigata University   29   124 - 124   1996

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • 左前頭葉内側面損傷による超皮質性運動失語における聴理解

    大槻 美佳, 相馬 芳明, 小野寺 理

    脳と神経   47 ( 11 )   1081 - 1085   1995.11

     More details

    Language:Japanese   Publisher:(株)医学書院  

    1)脳梗塞によって前頭葉内側面に主病巣をもつ超皮質性運動失語における聴理解を検討した.2)病巣が上前頭回から下・外側へ広がるほど聴理解成績は低下し,中前頭回に至ると語義理解障害も認められ,中前頭回が語義理解に関わっていると考えられた.3)上前頭回およびその皮質下に限局した損傷をもつ例も含め,すべての例に文理解障害が認められ,統辞・構文の何らかの処理障害が考えられた

    CiNii Article

    CiNii Books

    researchmap

  • MOLECULAR-CLONING OF MURINE HOMOLOG CDNA FOR DENTATORUBAL-PALLIDOLUYSIAN ATROPHY (DRPLA) GENE

    M OYAKE, O ONODERA, T SHIROISHI, H TAKANO, H TANAKA, K MORIWAKI, S TSUII

    AMERICAN JOURNAL OF HUMAN GENETICS   57 ( 4 )   848 - 848   1995.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • ISOLATION AND CHARACTERIZATION OF HUMAN CDNA CONTAINING POLYMORPHIC CAG TRINUCLEOTIDE REPEATS ISOLATED FROM HUMAN CEREBELLUM, FETAL BRAIN, STRIATUM AND NIGRA CDNA LIBRARIES

    S TSUII, S IGARASHI, Y TAKIYAMA, O ONODERA, H TANAKA

    AMERICAN JOURNAL OF HUMAN GENETICS   57 ( 4 )   863 - 863   1995.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • SOMATIC MOSAICISM OF THE CAG REPEAT EXPANSION IN THE CENTRAL-NERVOUS-SYSTEM AS A REFLECTION OF PROGRESSIVE NEURONAL CELL LOSS IN DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)

    H TAKANO, O ONODERA, H TAKAHASHI, S IGARASHI, M YAMADA, M OYAKE, T IKEUCHI, R KOIDE, H TANAKA, K IWABUCHI, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   57 ( 4 )   39 - 39   1995.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • GENETIC ASSOCIATION OF VERY-LOW-DENSITY LIPOPROTEIN (VLDL) RECEPTOR GENE LOCUS WITH SPORADIC ALZHEIMERS-DISEASE

    K OKUIZUMI, O ONODERA, Y NAMBA, K IKEDA, T YAMAMOTO, K SEK, A UEKI, S NANKO, H TANAKA, H TAKAHASHI, K OYANAGI, H MIZUSAWA, KANAZAWA, I, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   57 ( 4 )   1433 - 1433   1995.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • アポ蛋白EのgeneticsとAlzheimer病

    小野寺 理, 辻 省次

    医学のあゆみ   174 ( 6 )   574 - 578   1995.8

     More details

    Language:Japanese   Publisher:医歯薬出版(株)  

    researchmap

  • 9)精神分裂病におけるドーパミンD4受容体遺伝子の解析(I. 一般演題, 第6回新潟精神医学交流会)

    田中 敏恒, 高橋 誠, 亀田 謙介, 飯田 眞, 五十嵐 修一, 田中 一, 辻 省次, 小野寺 理

    新潟医学会雑誌   109 ( 8 )   410 - 410   1995.8

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • 8)精神分裂病におけるドーパミンD2受容体遺伝子の解析(I. 一般演題, 第6回新潟精神医学交流会)

    福島 昇, 田中 敏恒, 高橋 誠, 亀田 謙介, 飯田 眞, 五十嵐 修一, 田中 一, 辻 省次, 小野寺 理

    新潟医学会雑誌   109 ( 8 )   409 - 410   1995.8

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • Paraneoplastic cerebellar degeneration-Characterization of anti-Yo antibody and underlying cancer

    TANAKA Keiko, TANAKA Masami, ONODERA Osamu, TSUJI Shoji

    35 ( 7 )   770 - 774   1995.7

     More details

  • 10)精神分裂病におけるドーパミンD2受容体遺伝子の解析(I. 一般演題, 平成6年度新潟大学医学部精神医学教室同窓会集談会)

    福島 昇, 田中 敏恒, 高橋 誠, 亀田 謙介, 飯田 眞, 五十嵐 修一, 田中 一, 辻 省次, 小野寺 理, 高橋 邦明

    新潟医学会雑誌   109 ( 5 )   254 - 255   1995.5

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • 11)精神分裂病におけるドーパミンD4受容体遺伝子の解析(I. 一般演題, 平成6年度新潟大学医学部精神医学教室同窓会集談会)

    田中 敏恒, 亀田 謙介, 飯田 眞, 五十嵐 修一, 田中 一, 辻 省次, 小野寺 理, 高橋 邦明

    新潟医学会雑誌   109 ( 5 )   255 - 256   1995.5

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • Molecular Genetics of Dentatorubral-Pallidoluysian Atriohy(DRPLA)Symposium Pathophysiology of Hereditary Neurologic Diseases

    Reiji KOIDE, Takeshi IKEUCHI, Osamu ONODERA

    Niigata medical journal   109 ( 4 )   185 - 189   1995.4

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1996029836

  • 成人病と分子生物学 成人発症の神経筋疾患と分子生物学 多因子遺伝病のモデルとしてのアルツハイマー病

    小野寺 理, 辻 省次

    臨床成人病   25 ( 1 )   40 - 44   1995.1

     More details

    Language:Japanese   Publisher:(株)東京医学社  

    researchmap

  • Molecular cloning of a full-lenght cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of theexpanded alleles in the CNS

    Osamu Onodera, Mutsuo Oyake, Hiroki Takano

    Annual report, Brain Research Institute, Niigata University   28   96 - 96   1995

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • 歯状核赤核・炎蒼球ルイ体萎縮症(DRPLA )遺伝子変異[CAG リピート増大] の中枢神経系内体細胞モザイクと神経変成の関連についいて

    高野 弘基, 小野寺 理, 五十嵐 修一

    新潟大学脳研究所業績集   28   110 - 110   1995

     More details

    Language:Japanese   Publisher:新潟大学  

    CiNii Article

    CiNii Books

    researchmap

  • Lack of association between dopamine D4 receptor gene and schizophrenia

    Toshihisa Tanaka, Shuichi Igarashi, Osamu Onodera

    Annual report, Brain Research Institute, Niigata University   28   114 - 114   1995

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • 左前頭葉内側面損傷による超皮質性運動失語における聴理解

    大槻 美佳, 相馬 芳明, 小野寺 理[他]

    新潟大学脳研究所業績集   28   91   1995

     More details

    Language:Japanese   Publisher:新潟大学  

    CiNii Article

    CiNii Books

    researchmap

  • 後脊髄動脈症候群のMRI所見

    奥泉 薫, 若杉 三奈子, 小野寺 理

    臨床神経学   34 ( 11 )   1116 - 1120   1994.11

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    両下肢の深部感覚障害と錐体路徴候,膀胱直腸障害で急性発症し,臨床所見およびMRI所見より後脊髄動脈症候群と診断した1例を報告した。MRIでは脊髄後方に対称性にT2強調画像,プロトン密度画像で高信号を示す領域を認めた

    CiNii Article

    researchmap

  • 遺伝子が同定されている遺伝性疾患 副腎白質ジストロフィーの原因遺伝子の同定

    小池 亮子, 小野寺 理, 辻 省次

    実験医学   12 ( 6 )   681 - 683   1994.4

     More details

    Language:Japanese   Publisher:(株)羊土社  

    researchmap

  • 疾患遺伝子解明の最前線 ポジショナルクローニングに必要な手段・方法 cDNAライブラリーの作製法

    小野寺 理, 辻 省次

    実験医学   12 ( 6 )   610 - 614   1994.4

     More details

    Language:Japanese   Publisher:(株)羊土社  

    researchmap

  • UNSTABLE EXPANSION OF CAG REPEAT IN HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)

    T IKEUCHI, R KOIDE, O ONODERA, H TANAKA, S IGARASHI, K ENDO, S TSUJI, H TAKAHASHI, F IKUTA, R KONDO, A ISHIKAWA, T HAYASHI, M SAITO, H NAITO, A TOMODA, T MIIKE

    NEUROLOGY   44 ( 4 )   A360 - A360   1994.4

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LITTLE BROWN CO  

    Web of Science

    researchmap

  • 筋緊張性ジストロフィーにおける遺伝子不安定領域の変化と臨床症候の関連について

    江口 郁代, 小池 亮子, 小野寺 理

    臨床神経学   34 ( 2 )   118 - 123   1994.2

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    35名の筋緊張性ジストロフィー患者の末梢血ゲノムDNAを用いサザンハイブリダイゼーション法で原因遺伝子のCTG増大の程度を測定し,臨床症状との比較検討を行った。発症年齢が早いほど繰り返し配列が増大する傾向が認められた。40から45歳での日常生活動作で重症度分類をした場合,stage 1で0.33±0.17(M±SD)kbp,stage 2で2.58±1.42kbp,stage 3で4.75±0.93kbpの増大を示し各群で有意差があった。知的機能とCTG増大程度とも明らかな相関関係があった

    CiNii Article

    researchmap

  • リコンビナントYo蛋白を用いたELISA法によるParaneoplastic cerebellar degeneration患者での自己抗体の検出

    田中 恵子, 田中 正美, 小野寺 理

    脳と神経   46 ( 1 )   47 - 51   1994.1

     More details

    Language:Japanese   Publisher:(株)医学書院  

    リコンビナントYo蛋白を作成し,ELISAシステムを確立した。この方法により新たに3例見いだし,長期生存している1例については治療による抗体価への影響についても検討した。プラズマフェレーシス後に抗体価はむしろリバウンドのため上昇し,抗体価を低下させるためには抗原刺激となっている腫瘍に対する治療が重要である

    CiNii Article

    researchmap

  • GENETIC-LINKAGE ANALYSIS OF THE GENE FOR MACHADO-JOSEPH DISEASE

    M NISHIZAWA, Y TAKIYAMA, S KAWASHIMA, H SAKAMOTO, M YOSHIDA, H TANAKA, K ENDO, T INUZUKA, O ONODERA, S TSUJI

    CYTOGENETICS AND CELL GENETICS   66 ( 1 )   17 - 17   1994

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • Passive transfer and active immunization with the recombinant leucine-zippr (Yo) protein as an attempt to establish an animal model of paraneoplastic cer ebellar degeneration

    Tanaka Keiko, Tanaka Masami, Onodera Osamu

    Annual report, Brain Research Institute, Niigata University   27   110 - 110   1994

     More details

    Language:English   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • Trial to establish an animal model of paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibody 1.Mice strains bearing different MHC molecules produce antibodies on immunization with recombinant Yo protein, a T-dependent antigen, but do not cause Purkinje cell loss

    Tanaka Masami, Tanaka Keiko, Onodera Osamu

    Annual report, Brain Research Institute, Niigata University   27   111 - 111   1994

     More details

    Language:English   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • ApoE-ε4 and early-onset Alzheimers

    Okuizumi Kaoru, Onodera Osamu, Tanaka Hajime

    Annual report, Brain Research Institute, Niigata University   27   102 - 102   1994

     More details

    Language:English   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • Unstable expansion of CAG repeat in hereditarydentatorubral-pallidoluysian atrophy(DRPLA)

    Koide Reiji, Ikeuchi Takeshi, Onodera Osamu

    Annual report, Brain Research Institute, Niigata University   27   104 - 104   1994

     More details

    Language:English   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

  • ファブリー病症例におけるα-ガラクトシダーゼA遺伝子の単塩基置換

    宮北 靖, 田中 一, 小野寺 理

    心筋の構造と代謝   16   295 - 300   1993.10

     More details

    Language:Japanese   Publisher:(株)六法出版社  

    researchmap

  • DELETIONS OF ALD GENE IN JAPANESE ADRENOLEUKODYSTROPHY PATIENTS

    R KOIKE, O ONODERA, H TABE, K KANEKO, T MIYATAKE, J MOSSER, CO SARDE, JL MANDEL, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   53 ( 3 )   913 - 913   1993.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • ヒト疾患病因遺伝子同定のための技術的進歩 ポジショナルクローニングの概念,原理,方法

    小野寺 理, 辻 省次

    日本臨床   51 ( 9 )   2225 - 2233   1993.9

     More details

    Language:Japanese   Publisher:(株)日本臨床社  

    researchmap

  • THE GENE FOR MACHADO-JOSEPH DISEASE MAPS TO HUMAN CHROMOSOME-14Q

    K ENDO, H TANAKA, Y TAKIYAMA, M NISHIZAWA, S KAWASHIMA, H SAKAMOTO, Y KARUBE, H SHIMAZAKI, M SOUTOME, M YOSHIDA, T YUASA, Y HORIKAWA, K OYANAGI, H NAGAI, T KONDO, M SEGAWA, Y NOMURA, E YOSHIDA, N SAKURAI, T INUZUKA, O ONODERA, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   53 ( 3 )   997 - 997   1993.9

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • Isolation of Human Chromosome Specific Expressed SequenceTagged-Sites. : An Approach to Positional Cloning of Adrenoleukodystrophy

    Osamu ONODERA

    Niigata medical journal   107 ( 8 )   738 - 752   1993.8

     More details

    Language:Japanese   Publisher:Niigata University  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1994156767

  • THE GENE FOR MACHADO-JOSEPH DISEASE MAPS TO HUMAN CHROMOSOME-14Q

    Y TAKIYAMA, M NISHIZAWA, H TANAKA, S KAWASHIMA, H SAKAMOTO, Y KARUBE, H SHIMAZAKI, M SOUTOME, K ENDO, S OHTA, Y KAGAWA, KANAZAWA, I, Y MIZUNO, M YOSHIDA, T YUASA, Y HORIKAWA, K OYANAGI, H NAGAI, T KONDO, T INUZUKA, O ONODERA, S TSUJI

    NATURE GENETICS   4 ( 3 )   300 - 304   1993.7

     More details

    Language:English   Publisher:NATURE PUBLISHING CO  

    Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Z(max) = 9.719).

    Web of Science

    researchmap

  • CA dinucleotide repeat polymorphismを用いたDuchenne型筋ジストロフィーの非保因者診断(第2報)

    近藤 浩, 青木 賢樹, 小野寺 理

    厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィーの臨床病態と遺伝相談及び疫学に関する研究   平成4年度   47 - 49   1993.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    researchmap

  • 筋緊張性ジストロフィー症における遺伝子不安定領域の変化と臨床症状の関連について

    田中 恵子, 江口 郁代, 小野寺 理

    厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィー及び関連疾患の成因と治療法開発に関する研究   平成4年度   88 - 91   1993.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    researchmap

  • Adrenoleukodystrophy遺伝子のポジショナルクローニングに向けてのストラテジー 染色体特異的,組織特異的cDNAの単離について

    辻 省次, 田部 浩行, 小野寺 理

    厚生省精神・神経疾患研究委託費研究報告書 遺伝子解析による神経疾患発現機構に関する研究   平成4年度   69 - 73   1993.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    Xq28の領域に存在し脳で発現している遺伝子を同定する目的で,ヒト脳cDNAライブラリーをプローブとしてヒトXq24-Xqter由来のクローン化したゲノムDNAに対してハイブリダイゼーションを行い,1個の陽性クローンを得た。ホモロジー検索では既知のものとの相同性はなかった。この遺伝子は中枢神経,筋,肝,脾,精巣,副腎で発現がみられた。この遺伝子は,Xq28内のcolor pigment geneを含む900Kbpの領域に存在し,アルツハイマー病の原因遺伝子の候補遺伝子となりうると考えられる。このような方法は,染色体の他の領域に存在する遺伝子についても有用と考えられる

    researchmap

  • オリーブ橋小脳萎縮症(OPCA)とMachado-Joseph病(MJD)におけるMRI所見 橋横走線維の診断的有用性について

    出塚 次郎, 小野寺 理, 湯浅 竜彦

    臨床神経学   33 ( 3 )   289 - 293   1993.3

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    MRI T2強調画像における橋横走線維の信号強度の増加所見がOPCAとMachado-Joseph病(MJD)の鑑別診断に有用であるか否かを検索した。OPCA群18例では全例でT2強調画像における橋横走線維の信号強度増加が認められたのに対し,MJD群では同所見は全く認められなかった。橋横走線維のT2強調画像における高信号化はOPCAで特徴的であり,MJDでは橋被蓋部の萎縮が特徴的であった

    CiNii Article

    CiNii Books

    researchmap

  • X染色体の解析と伴性神経疾患遺伝子

    小野寺 理, 金子 清俊, 田部 浩行

    蛋白質・核酸・酵素   38 ( 3 )   354 - 360   1993.2

     More details

    Language:Japanese   Publisher:共立出版(株)  

    researchmap

  • 1)ベーチェット病にてシクロスポリン長期投与中に脳トキソプラズマ症を併発した1例(演題 3, 第27回新潟画像医学研究会)

    滝川 真吾, 出塚 次郎, 小野寺 理, 中野 亮一, 米持 洋介, 田中 恵子, 辻 省次, 高橋 均, 阿部 達也, 伊藤 寿介, 阿部 博史

    新潟医学会雑誌   107 ( 2 )   189 - 190   1993.2

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

  • ヒトゲノム解析の新展開 巨大ゲノムDNAをクローン化する コスミドcontigの作製と遺伝子の探索

    金子 清俊, 田部 浩行, 小野寺 理

    Molecular Medicine   30 ( 2 )   194 - 200   1993.1

     More details

    Language:Japanese   Publisher:(株)中山書店  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1994068837

  • ISOLATION OF 11 NEW EXPRESSED SEQUENCE-TAGGED SITES FROM HUMAN-CHROMOSOME REGION XQ24-]QTER

    O ONODERA, H KOBAYASHI, K KANEKO, ST WARREN, T MIYATAKE, S TSUJI

    CYTOGENETICS AND CELL GENETICS   64 ( 3-4 )   190 - 190   1993

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:KARGER  

    Web of Science

    researchmap

  • ポジショナルクローニングによる疾患遺伝子の解明 副腎白質ジストロフィーのポジショナルクローニングへのアプローチ

    小野寺 理, 小林 央, 田部 浩行

    細胞工学   11 ( 10 )   739 - 744   1992.10

     More details

    Language:Japanese   Publisher:(株)学研メディカル秀潤社  

    researchmap

  • CA dinucleotide repeat polymorphismを用いたDuchenne型筋ジストロフィーの非保因者診断

    保住 功, 小野寺 理, 近藤 類

    厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィーの臨床病態と遺伝相談及び疫学に関する研究   平成3年度   59 - 61   1992.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    researchmap

  • CONSTRUCTION OF HUMAN XQ24-QTER HNCDNA LIBRARY HIGHLY ENRICHED IN HUMAN-DERIVED HNCDNA

    O ONODERA, H KOBAYASHI, ST WARREN, T MIYATAKE, S TSUJI

    AMERICAN JOURNAL OF HUMAN GENETICS   49 ( 4 )   444 - 444   1991.10

     More details

    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:UNIV CHICAGO PRESS  

    Web of Science

    researchmap

  • 4)両側視床に病変を認めたBehcet病の1例(I.一般演題, 第23回新潟画像医学研究会)

    菊川 公紀, 小野寺 理, 米田 誠, 宮下 光太郎, 杉谷 想一, 湯浅 龍彦, 宮武 正

    新潟医学会雑誌   104 ( 11 )   977 - 978   1990.11

     More details

    Language:Japanese   Publisher:新潟医学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/1992047315

  • A case of rigid spine syndrome with rimmed vacuole

    O. Onodera, M. Yamazaki, T. Atsumi, T. Miyatake, T. Izumi

    Clinical Neurology   30 ( 5 )   516 - 519   1990

     More details

    Language:Japanese  

    Scopus

    PubMed

    researchmap

  • 運動後心停止の1例 運動負荷試験による自律神経関与の評価

    小野寺 理

    日本内科学会雑誌   78 ( 5 )   720 - 720   1989.5

     More details

    Language:Japanese   Publisher:(一社)日本内科学会  

    researchmap

  • Rigid spine syndromeに見られたrimmed vacuoleの筋組織化学的検討

    小野寺 理

    臨床神経学   28 ( 12 )   1493 - 1493   1988.12

     More details

    Language:Japanese   Publisher:(一社)日本神経学会  

    researchmap

  • Rimmed vacuoleを認めたRigid spine syndromeの一例

    宮武 正, 小野寺 理, 山崎 元義

    厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィー症及び関連疾患の病態とその病因に関する研究   昭和62年度   31 - 35   1988.3

     More details

    Language:Japanese   Publisher:厚生省精神・神経疾患研究班  

    researchmap

▶ display all

Industrial property rights

  • HTRA1変異と家族性虚血性脳小血管病との関連

    辻 省次, 小野寺 理

     More details

    Applicant:国立大学法人 東京大学

    Application no:特願2011-545523  Date applied:2010.4

    Announcement no:特表2012-523819  Date announced:2012.10

    J-GLOBAL

    researchmap

  • HTRA1変異と家族性虚血性脳小血管病との関連

    辻 省次, 小野寺 理

     More details

    Applicant:国立大学法人 東京大学

    Application no:特願2011-545523  Date applied:2010.4

    Patent/Registration no:特許第5737721号  Date issued:2015.5

    J-GLOBAL

    researchmap

Awards

  • 新潟日報文化賞

    2021.11  

     More details

  • 新潟大学学長表彰

    2009   新潟大学  

    小野寺 理ら

     More details

  • 日本神経学会賞

    2008   日本神経学会  

    小野寺 理

     More details

  • ベルツ賞 佳作賞

    2002  

    辻省次, 小野寺, 理 ら

     More details

Research Projects

  • 脳小血管の細胞外基質の摂動を起こす細胞群の同定と、その制御機構の解読

    Grant number:22H00466

    2022.4 - 2025.3

    System name:科学研究費助成事業 基盤研究(A)

    Research category:基盤研究(A)

    Awarding organization:日本学術振興会

    小野寺 理, 加藤 泰介, 塚田 啓道, 齋藤 理恵

      More details

    Grant amount:\42510000 ( Direct Cost: \32700000 、 Indirect Cost:\9810000 )

    researchmap

  • 脊髄運動ニューロン固有のRNA制御プログラムとALS病態の関連

    Grant number:19H03543

    2019.4 - 2023.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    矢野 真人, 小野寺 理, 矢野 佳芳

      More details

    Grant amount:\16250000 ( Direct Cost: \12500000 、 Indirect Cost:\3750000 )

    本研究は、運動ニューロンに特徴的な発現を示すRNA結合蛋白質を選別し、得られたRNA結合蛋白質を機能解析をする事で、脊髄運動ニューロン固有のRNA制御プログラムを解明し、その生理的機能及びALSなどの運動ニューロン病の病態との関連性を明らかするものである。我々は、これまで約1500種類存在すると言われるRNA結合蛋白質の中で、Qki5蛋白質が運動ニューロン特異的な発現を示す唯一のRNA結合蛋白質であることを見出した。次に、我々が行ってきた生体内RNA結合蛋白質機能解析戦略である1塩基解像度の蛋白質-RNA相互作用マッピング解析HITS-CLIPとRNAシーケンス技術にマウス遺伝学を組み合わせた解析を実施し、脊髄運動ニューロン固有のRNA制御プログラムを解明し、Qki5の生理的機能及び病態との関連性の解析を進めている。これまでに、発生段階および成体の脊髄における免疫組織学的解析を行い、Qki5蛋白質が神経細胞の中で運動ニューロンにおいてのみ発現する特徴的な発現パターンを有していることが明らかとなった。さらにヒトiPS細胞由来神経細胞を用いたシングルセルトランスクリプトーム解析を行ったところ、免疫組織学的解析で得られた特徴的なパターンと一致し、Qki5の発現は、運動ニューロン特異的分子isl-1遺伝子と同じクラスターに存在していることが明らかとなった。さらに、Qki5のHITS-CLIP解析およびQki5をノックダウンさせた運動ニューロンを用いたトランスクリプトーム解析を実施し運動ニューロン固有の標的下流RNA群の探索を行い、新たなQki5の標的遺伝子群や新規のCryptic exonの発見、また運動ニューロン変性と密接に関わる標的遺伝子群を同定することができた。運動ニューロン特異的CreドライバーマウスとQk遺伝子のコンディショナル欠損マウスを交配し、分子生物学的解析、組織学的解析および行動学的解析による表現型解析を進めている。

    researchmap

  • Approach to neurodegenerative disorders by elucidation of the excretion pathway of the brain.

    Grant number:19H01043

    2019.4 - 2022.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    ONODERA OSMAU

      More details

    Grant amount:\45500000 ( Direct Cost: \35000000 、 Indirect Cost:\10500000 )

    We found that HTRA1-deficient mice serve as a model animal for age-related changes similar to those in small cerebral blood vessels. Quantitative DIA proteomics and GO analysis revealed that the main abnormality is in the extracellular matrix and matrizomes, with fibronectin as a hub protein as a starting point. Accumulation of fibronectin is a common phenomenon in age-related cerebral microvascular changes. We found that candesartan suppressed this change. In addition, they found that candesartan also reduced cerebral blood flow and vasodilatability. In addition, they found that treatment with candesartan improved the vasodilatory changes. The results clearly indicate that extracellular proteostasis plays a major role in the homeostasis of proteins in the brain.

    researchmap

  • 成人発症白質脳症の実際と有効な医療施策に関する研究班

    2018 - 2020

    System name:領域別基盤研究分野における難病の医療水準の向上や患者のQOL向上に資する研究(30080201)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\8000000 ( Direct Cost: \4000000 、 Indirect Cost:\3000000 )

    researchmap

  • Tauopathy affecting astrocytes: diversity in the tau pathology and the astrocytic molecular feature

    Grant number:17H03554

    2017.4 - 2020.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Takahashi Hitoshi

      More details

    Grant amount:\17290000 ( Direct Cost: \13300000 、 Indirect Cost:\3990000 )

    Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised by tau-positive globular glial inclusions, such as globular astrocytic inclusions (GAIs).Neuropathologically, we identified 6 cases of GTT and classified 3 and 3 cases into Type II and Type III, respectively. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than Type II. Neuronal cytoplasmic inclusions (NCIs) were divisible into three subgroups in terms of shape: diffuse granular, thick-cord-like, and round/horseshoe-shaped structures.Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. These findings indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

    researchmap

  • ポリグルタミン病に対する蛋白質凝集阻害薬の開発(大阪大学B-49)

    2017 - 2019

    System name:シーズB

    Awarding organization:医療研究開発推進事業費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\44000000 ( Direct Cost: \22000000 、 Indirect Cost:\6600000 )

    researchmap

  • TGF-βシグナルを標的にしたCARASILの新規治療シーズの探索

    2017 - 2019

    System name:希少難治性疾患に対する画期的な医薬品医療機器等の実用化に関する研究:薬事承認を目指すシーズ探索研究(ステップ0)

    Awarding organization:日本医療研究開発機構研究費

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\36800000 ( Direct Cost: \18400000 、 Indirect Cost:\5520000 )

    researchmap

  • ゲノム編集を用いた優性遺伝性中枢神経疾患の治療方法の開発

    2017 - 2019

    System name:【IRUD Beyond+ゲノム編集】希少難治性疾患・未診断疾患領域における革新的開発候補物の非臨床POC確立を目指す研究

    Awarding organization:日本医療研究開発機構研究費

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\40000002 ( Direct Cost: \20000001 、 Indirect Cost:\5999999 )

    researchmap

  • Strategies for overcoming vascular dementia focusing on dynamic functions of cerebral small vessels.

    Grant number:16H02656

    2016.4 - 2019.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    Onodera Osamu

      More details

    Grant amount:\46670000 ( Direct Cost: \35900000 、 Indirect Cost:\10770000 )

    Overcoming dementia is an urgent task, and vascular dementia is one of the leading causes. Recently, a cerebral small vessel is noted and is called cerebral small vessel disease. Disorders of neural activity-dependent blood supply regulatory mechanisms have been advocated as the pathological condition. However, its molecular mechanism has not been well characterized. We isolated the causative gene for hereditary cerebral small vessel disease, HTRA1, and clarified that this disease is due to an increase in tissue growth factor signal. Furthermore, we defined the molecular pathogenesis of cerebral small vessel disease in mice with degeneration of smooth muscle and pericytes similar to sporadic cerebrovascular disease.

    researchmap

  • Elucidation of the significance of MAPT polymorphism associated with sporadic tauopathies by using genome editing method.

    Grant number:16K15479

    2016.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    Onodera Osamu

      More details

    Grant amount:\3380000 ( Direct Cost: \2600000 、 Indirect Cost:\780000 )

    MAPT gene polymorphism is known in diseases that allow accumulation of tau, but it was difficult to analyze the significance of the polymorphism. By using the CORRECT method applying CRISPR-Cas 9 method, we introduce disease-related MAPT polymorphisms and investigate the expression level of tau gene and its effect on splicing. The introduction rate of genome editing improves 1.0% by standard method up to 4.5%. However, the efficiency was still low, and it was revealed that there is a possibility that it may be markedly different depending on genes. When splicing of MAPT was examined using the edited cells, it was confirmed that the ratio of 4R/3Rtau was increased. This cell line can be applied to drug screening to improve the ratio.

    researchmap

  • 重合体形成阻害を標的としたポリグルタミン病の新規治療法開発

    Grant number:16K09670

    2016.4 - 2018.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    他田 正義, 小野寺 理

      More details

    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    (1) 重合体形成阻害を分子標的としたモデル線虫による薬剤スクリーニング:初期スクリーニングで得られた約300の候補薬の中から既に本邦で臨床使用されている25薬剤を抽出し、ポリグルタミン病モデル線虫を用いて治療効果を検討した。その結果、6薬剤がモデル線虫の封入体面積・総数を有意に減少させた。この中で、既に広く臨床使用されている QAI-39095 に注目し、モデル線虫の表現型解析および生化学的解析を行った。QAI-39095投与により、封入体数・面積の減少、運動能の改善、寿命の延長、重合体量の減少が生じることを確認した。
    (2) マチャド・ジョセフ病患者由来線維芽細胞からのiPS細胞の樹立:熊本大学発生医学研究所の協力を得て、SCA3患者2名の皮膚組織からiPS細胞の樹立を試みたが、不成功に終わった。
    (3) 小脳性運動失調の新たな定量評価法の開発:iPad を用いた上肢運動機能評価システム iPatax (iPad Application for Evaluating Ataxia) を開発した。健常者および小脳失調症患者を対象とした解析で、視標追跡課題における速度の変動係数が小脳性運動失調の臨床重症度と高い正の相関を示すことを明らかにした。さらに、脊髄小脳変性症 (SCD) 患者の自然歴や治療効果判定に iPatax視標追跡検査が有用であることを示した。また、Kinectセンサーを用いた3次元歩行解析システムを開発した。
    (4) 患者に対する治療介入試験:SCD患者29例を対象として、禁煙薬であるバレニクリン酒石酸塩の有効性と安全性を検討した。8週間の服用で嘔気を7例 (24.1%) に認めたが、重篤な副作用は認めなかった。高用量群(2mg/日)と低用量群(0.5mg/日)の2群比較において、8週間の服用により、高用量群では低用量群に比して臨床評価スケールSARAの歩行項目が有意に改善した。また、治療効果判定に iPatax視標追跡検査が有用であることを示した。

    researchmap

  • 成人発症白質脳症の医療基盤に関する調査研究班

    2016 - 2017

    System name:領域別基盤研究分野(客観的な指標に基づく疾病概念が確立されている疾病が対象)(28080401)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3324000 ( Direct Cost: \1662000 、 Indirect Cost:\1038000 )

    researchmap

  • Brain Protein Aging and Dementia Control(International Research Activities Supporting Program)

    Grant number:15K21714

    2015.11 - 2019.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Research category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Awarding organization:Japan Society for the Promotion of Science

    Sobue Gen, YANAI kazuhiko, TAKASHIMA akihiko, HASEGAWA masato, ONODERA osamu, OKANO hideyuki, SAHARA naruhiko, ADACHI hiroaki, ANDO kanae, AKAMATSU wado, UCHIYAMA keiji, OHTA etsuro, OKADA yohei, ONO masahiro, KAIBUCHI kozo, KATO koichi, SAKAGUCHI suehiro, TAINAKA kazuki, TAKAHASHI ryosuke, TANAKA hiromitsu, NAGAI yoshitaka, HASHIMOTO tadafumi, HASEGAWA takafumi, HAMADA kozo, FUKADA masaki, FUKUDA mitsunori, FURUKAWA yoshiaki, MATSUI hideaki, MIZUTA kotaro, MOCHIZUKI hideki, YAMADA kaoru, MORISHITA hideaki, HISANAGA shinichi

      More details

    Grant amount:\58760000 ( Direct Cost: \45200000 、 Indirect Cost:\13560000 )

    Firstly, we established the secretariat and relating committees in order to promote the international joint research and global communications.During the past four years, 43 researchers presented their research achievements abroad, and 24 distinguished foreign researchers were invited to Japan by our programs. With more than 500 participants in total, we held two international symposiums, the international workshop, the international tau symposium as well as the joint meeting with PACTALS to promote the joint research and the establishment of research networks on a global basis.
    Notably, we succeeded to publish eBook composed by 22 papers in “Frontiers in Neuroscience.” This was highly effective to appeal our research achievements to the world. Through our original website, annual reports of research activities and annual newsletters, our research achievements were also effectively and successfully notified to researchers, especially those of relating to our research fields.

    researchmap

  • Crosstalk between stress granules and autophagy in protein degradation

    Grant number:15H04704

    2015.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Fujii Masahiro, Komatsu Masaaki, Takahashi Masahiko, Kageyama Shun, Hara Toshifumi, Higuchi Masaya, Saito Kousuke, Koyama Akihide, Katsuragi Yoshinori, Kakihana Taichi

      More details

    Grant amount:\16900000 ( Direct Cost: \13000000 、 Indirect Cost:\3900000 )

    USP10 plays an important role in the formation of stress granule. I established systemic USP10-knockout (USP10-KO) mice. USP10-KO mice developed pancytopenia, and died within 300 days. This pancytopenia was completely restored by transplantation of normal bone marrows into USP10-KO mice. Furthermore, I found that apoptosis of hematopoietic stem cells is aggravated in USP10-KO mice. SCL (stem cell factor) inhibits the apoptosis of hematopoietic stem cells, but this inhibition was significantly attenuated by USP10 depletion in hematopoietic stem cells. USP10 mutants indicated that deubiquitinase activity of USP10 is critical for inhibition of apoptosis of hematopoietic stem cells. The present study suggests that USP10 and stress granules participate in the maintenance of hematopoietic stem cells.

    researchmap

  • 新規臨床評価方法によるフォールディング病の化学シャペロンでの病態抑制効果の検討

    2015

    System name:障害者対策総合研究事業(新規)

    Awarding organization:障害者対策総合研究開発事業

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\14042000 ( Direct Cost: \7021000 、 Indirect Cost:\2101978 )

    researchmap

  • Mechanism of protein aging from the point of turbulence of nucleic acid metabolism or its exclusion mechanism.

    Grant number:26117006

    2014.7 - 2019.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Research category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Awarding organization:Japan Society for the Promotion of Science

    Onodera Osamu, Kakita Akiyoshi

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\113360000 ( Direct Cost: \87200000 、 Indirect Cost:\26160000 )

    Proteins that cause dementia are "transformed into pathogenic proteins and accumulated" in "selected nervous systems" with aging. This process is accompanied by "quantitative and qualitative alterations in proteins." The amount of protein is controlled by production and degradation, production is controlled by mRNA, and degradation is controlled by intracellular degradation systems and extracellular efflux mechanisms. We found that the RNA metabolism mechanism of TDP-43 causing age-related neurodegenerative diseases is disturbed. Furthermore, by disrupting RNA metabolism in vivo, we succeeded in causing fragmentation of TDP-43 and inducing apoptosis.

    researchmap

  • Amyotrophic Lateral Sclerosis and TDP-43: Elucidation of molecular neuropathology in terms of spread from its beginning

    Grant number:26250017

    2014.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    Takahashi Hitoshi, KAKITA Akiyoshi, SAKIMURA Kenji, IKEUCHI Takeshi

      More details

    Grant amount:\39780000 ( Direct Cost: \30600000 、 Indirect Cost:\9180000 )

    We found that TDP-43 regulates the level of-its-own protein by alternative splicing within exon 6. Surprisingly, we found that the proportion of TDP-43 mRNA associated with this autoregulation increases in the spinal cord of ALS patients. It was confirmed that this mutant co-localized with TDP-43 immuno-positive inclusion body in anterior horn cells of ALS patients. This suggested that this abnormal protein may be the beginning of ALS lesion.
    We reevaluated the cortical TDP-43 pathology in cases of sporadic ALS, using semi-quantitative estimation of pTDP-43-positive dystrophic neurite in the temporal neocortex,the case were divided into three groups, types 1, 2a and 2b. Type 2b has characteristic clinicopathological features. Considering the patient survaival time and severity of motor neuron loss, each group was regarded as independent subtype, indicating that transition from type 1 to type 2a, or from type 2a to type 2b during the disease course appeared unlikely.

    researchmap

  • Heterogeneity of TDP-43 pathology and clinicopathologic correlations in sporadic amyotrophic lateral sclerosis

    Grant number:26640029

    2014.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    TAKAHASHI Hitoshi, TOYOSHIMA Yasuko, TADA Mari, ONODERA Osamu

      More details

    Grant amount:\3380000 ( Direct Cost: \2600000 、 Indirect Cost:\780000 )

    A nuclear protein,TDP-43, is the major pathological protein in ALS. We attempted to clarify the corticalpathology in cases of sporadic amyotrophic lateral sclerosis (ALS: n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (classical ALS: ALS-C, n = 63), and those with such inclusions (ALS with temporal lesions: ALS-T, n = 33). Furthermore, the ALS-T cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: ALS-T/few DNs (n = 22) and ALS-T/many DNs (n = 11). Considering the patient survival time and severity of motor neuron loss in each group, transition from ALS-C to ALS-T, or from ALS-T/few DNs to ALS-T/many DNs during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype.

    researchmap

  • Establishment of TDP-43 C-terminal deficient mice using zinc finger nuclease and application to the model for amyotrophic lateral sclerosis

    Grant number:25461271

    2013.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SATO TOSHIYA, KODERA YOSHIO, ONODERA OSAMU

      More details

    Grant amount:\5070000 ( Direct Cost: \3900000 、 Indirect Cost:\1170000 )

    To investigate the physiological functions of the C-terminal region (CTR) of TDP-43, we established eight lines of CTR deficient mice using zinc finger nuclease. Mutant TDP-43 mice carrying a deletion within 6 amino acids in the middle of CTR (A) appeared normal even in the homozygote, whereas homozygous mice carrying a large deletion of the N- (B; 262-348) or C-terminal (C; 345-414) half of CTR showed embryonic lethality. In the brains of heterozygous B or C mice, a comparable level of the truncated protein corresponding to the large deletion was observed only in B mice. The truncated TDP-43 was exclusively in the cytoplasm fraction, thus it could not show physiological function in the nucleus. These results show N-terminal half of CTR is essential for maintaining nuclear function of TDP-43, whereas C-terminal half of CTR is important for the protein stability.

    researchmap

  • Approach to cerebral small vessel disease: lesson from CARASIL.

    Grant number:25293200

    2013.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Onodera Osamu, SATO Toshiya, TOYOSHIMA Yasuko, KOYAMA Akihide

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\18720000 ( Direct Cost: \14400000 、 Indirect Cost:\4320000 )

    Cerebral small-vessel disease (CSVD) is a neurological disorder involving white matter lesions. CSVD is frequently observed in an elderly population and causes cognitive impairment and motor dysfunction. However little is known about a molecular pathogenesis for CSVD. Cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), an autosomal-recessive inherited cerebral small vessel disease (CSVD), involves severe leukoaraiosis, multiple lacunar infarcts, early-onset alopecia, and spondylosis deformans without hypertension. High-temperature requirement serine peptidase A1 (HTRA1) gene mutations cause CARASIL by decreasing HTRA1 protease activity. We have investigated the HTRA1 deficit mouse. We found that these mice showed mural cell and internal elastic membrane degeneration. We found fibronectin and protein X accumulates at the internal membrane. The pathological findings of the mouse resemble those of CARASIL as well as sporadic CSVD.

    researchmap

  • Developing new therapeutic drugs that inhibit oligomer formation of polyglutamine disease proteins based on the hypothesis of oligomer toxicity in polyglutamine diseases

    Grant number:25461272

    2013.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Tada Masayoshi, Onodera Osamu

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    We developed new therapeutic drugs that inhibit oligomer formation of polyglutamine disease proteins based on the hypothesis of oligomer toxicity in polyglutamine diseases. Using a disease nematode model, we found a small compound that inhibit oligomer formation of disease proteins and ameliorate motor function of the nematode model. We also developed a novel system using iPad for the quantitative assessment of cerebellar ataxia. In addition, we started a clinical trial to investigate the safety and efficiency of varenicline (Champix), a prescription medication used to treat nicotine addiction, in the treatment of spinocerebellar degenerations.

    researchmap

  • Autoreguation of TDP-43 in ALS

    Grant number:25253065

    2013.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    Nishizawa Masatoyo, ONODERA Osamu, ISHIHARA Tomohiko, KAKITA Akiyoshi, SATO Toshiya

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\45890000 ( Direct Cost: \35300000 、 Indirect Cost:\10590000 )

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. We show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons; especially neurons with mislocalized TDP-43; the amount of TARDBP mRNA is increased in the cytoplasm. Our observations suggests that that the absence of nuclear TDP-43 induces an abnormal autoregulation.

    researchmap

  • Identification of splicing factors that bind to expanded GGGGCC repeat and TDP-43 mRNA

    Grant number:25670417

    2013.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    Onodera Osamu

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Expansion of a GGGGCC (G4C2) repeat in the first intron of C9ORF72 is the most common cause of familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS). TAR DNA-binding protein 43 (TDP-43), encoded by TARDBP, is a major component of neuronal cytoplasmic inclusions, which are observed in affected neurons in patients with ALS. TDP-43 pathology is also observed in patients with the G4C2 repeat expansion. We have hypothesized that the repeat expansion might cause dysregulation of the alternative splicing of TDP-43 mRNA. We generated (G4C2)9 repeats as a normal control or (G4C2)82 repeats expression vectors and identified binding proteins. We transfected these RBPs siRNA into HEK293T cells and analyzed the TDP-43 alternative splicing. We performed in-situ hybridization and immunofluorescent double staining analysis using HEK293T cells. We found two G4C2 binding RBPs. However, we could not observe these proteins co-localized with (G4C2)82 repeats foci.

    researchmap

  • U12依存性スプライシングとALSサーキットパソロジー

    Grant number:25110714

    2013.4 - 2015.3

    System name:科学研究費助成事業 新学術領域研究(研究領域提案型)

    Research category:新学術領域研究(研究領域提案型)

    Awarding organization:日本学術振興会

    小野寺 理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\15600000 ( Direct Cost: \12000000 、 Indirect Cost:\3600000 )

    ALSのサーキットパソロジーには次の2点1) TDP-43病理像の錐体路への選択性,2)細胞死の運動神経への選択性の解明が必要であり,各々について研究を進めた.本年度は,引き続きTDP-43病理像の錐体路への選択性についてて検討した.TDP-43遺伝子変異,及び C9ORF72変異によるALS/FTLDの発見は,組織への選択性を規定する因子が,遺伝子ではなく,侵される細胞側の特性にあることを示す.その細胞側の特性として,我々は細胞でのTDP-43 mRNA の制御機構の相違を考え,これを検討した.これに示唆を与える事実として,まずTDP-43は自己量の制御機構をもち,最終エクソンがその制御の主体を担っている.同部は複数のスプライシング部位とpolyA結合部位をもつ.TDP-43 mRNA は核内に多量に存在する.また制御機構の乱れを示唆する所見として,疾患関連変異が最終エクソンに集中する.TDP-43変異を持つ患者由来人工多能性幹細胞由来の運動神経細胞ではTDP-43の増加が示唆されていることがあげられる.そこでTDP-43自身のmRNAの脊髄運動神経細胞での検討を行った.神経細胞でのTDP-43 mRNAの細胞内での核,細胞質における存在比率と,を検討した.in situ hybridization 法を用い高感度に,かつ定量的にTDP-43 mRNAを測定できる系を開発し,本方法による検討を行った.その結果ALS脊髄運動神経細胞においてTDP-43 mRNAの細胞内局在の変化を同定した.本発見は細胞毎のTDP-43量調節について検討を加える基盤となる.

    researchmap

  • 遺伝性脳小血管病およびその類縁疾患の診断基準の確立と治療法の研究

    2013

    System name:難治性疾患等克服研究事業(難治性疾患克服研究事業)(継続)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2800000 ( Direct Cost: \1400000 、 Indirect Cost:\1500000 )

    researchmap

  • 遺伝性脳小血管病およびその類縁疾患の診断基準の確立と治療法の研究

    2012 - 2013

    System name:難治性疾患等克服研究事業(新規)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4000000 ( Direct Cost: \2000000 、 Indirect Cost:\1500000 )

    researchmap

  • ALS and TDP-43: Dose the splicing failure underlie the pathogenesis of ALS?

    Grant number:23240049

    2011.4 - 2014.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    HITOSHI Takahashi, TOYOSHIMA Yasuko, ONODERA Osamu, KUWANO Ryozo, SAKIMURA Kenji, KAKITA Akiyoshi, YOKOYAMA Minesuke

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\45890000 ( Direct Cost: \35300000 、 Indirect Cost:\10590000 )

    Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease. For a development of therapeutic methods for this disease, we investigated the splicing variants of TDP-43, and its own function associated with splicing for other genes. We found that THP-43 has menu splicing variants, and investigate the mechanism how splicing factors influence this splicing. In addition, we found some of the mutation with ALS10, which is caused by a mutation in TDP-43, affects the efficiency of its own splicing. These findings may open new avenue for the investigation of the pathogenesis of ALS.

    researchmap

  • 細胞内膜構造に注目した運動神経病の画期的な治療法の開発

    2011 - 2012

    System name:障害者対策総合研究事業(継続)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17694000 ( Direct Cost: \8847000 、 Indirect Cost:\4903000 )

    researchmap

  • An immunohistochemical study on nuclear bodies in neurodegenerativediseases with abnormal protein aggregates

    Grant number:23659184

    2011 - 2012

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    TAKAHASHI Hitoshi, TOYOSHIMA Yasuko, ONODERA Osamu

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    The kinetics of two nuclear bodies, PML and Cajal bodies, werestudied in multiple system atrophy (MSA) and sporadic amyotrophic lateral sclerosis (ALS),respectively. In MSA, in the nuclei of the pontine nuclei neurons, PML bodies were found tobe deformed in the presence of r-synuclein-positive intranuclear inclusions: the roundstructures changed to rod-like or linear abnormal ones. Statistically, the entire volume ofPML bodies was significantly decreased in MSA group (n=5) than in control group (n=5). InALS, in the nuclei of the lumbar anterior horn cells, the number of Cajal bodies was significantly decreased in ALS group (n=5: 8.06+/-4.41) than in control group (n=5:17.19+/-4.09). It is tempting to speculate that in MSA and ALS, these decreases of PML andCajal bodies, which are associated with neuronal viability, play an important role inneuronal cell death in relation to abnormalities of r-synuclein and TDP-43, respectively.

    researchmap

  • 遺伝性脳小血管病の病態機序の解明と治療法の開発

    2011

    System name:難治性疾患克服研究事業(継続)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\10200000 ( Direct Cost: \5100000 、 Indirect Cost:\3000000 )

    researchmap

  • Molecular pathogenesis of cerebral small vessel disease.

    Grant number:22390174

    2010 - 2013

    System name:Grants-in-Aid for Scientific Research(基盤研究(B))

    Research category:基盤研究(B)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Osamu ONODERA, 豊島 靖子, Toshiya SATO, Hiroaki NOZAKI

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\18850000 ( Direct Cost: \14500000 、 Indirect Cost:\4350000 )

    Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to the HTRA protein family, whose members have dual activities as chaperones and serine proteases and also repress transforming growth factor-beta (TGF-beta) family signaling. We investigated the molecular pathogenesis of CARASIL in HTRA1 null mouse. By immunohistochemical analysis we have found the alteration in cerebral small vessels in the model. This model mouse could be useful for the investigation of the pathogenesis of cerebral small vessel disease.

    researchmap

  • 細胞内膜構造に注目した運動神経病の画期的な治療法の開発

    2010 - 2012

    System name:障害者対策総合研究事業(新規)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\19000000 ( Direct Cost: \9500000 、 Indirect Cost:\5000000 )

    researchmap

  • Molecular pathogenesis of ALS: approach from TDP-43 function.

    Grant number:22249036

    2010 - 2012

    System name:Grants-in-Aid for Scientific Research(基盤研究(A))

    Research category:基盤研究(A)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Masatoyo NISHIZAWA, 阿部 学, Ryozo KUWANO, Toshiya SATOU, 横関 明男, Osamu ONODERA, Akiyoshi KAKITA, Manabu ABE

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\48880000 ( Direct Cost: \37600000 、 Indirect Cost:\11280000 )

    Disappearance of TAR-DNA binding protein 43 kDa (TDP-43) from the nucleuscontributes to the pathogenesis of amyotrophic lateral sclerosis (ALS), but the nuclearfunction of TDP-43 is not yet fully understood. TDP-43 associates with nuclear bodiesincluding Gemini of coiled bodies (GEMs). GEMs contribute to the biogenesis ofuridine-rich small nuclear RNA (U snRNA), a component of splicing machinery. Thenumber of GEMs and a subset of U snRNAs decrease in spinal muscular atrophy, alower motor neuron disease, suggesting that alteration of U snRNAs may also underliethe molecular pathogenesis of ALS. We investigated the number of GEMs andU11/12-type small nuclear ribonucleoproteins (snRNP) by immunohistochemistry andthe level of U snRNAs using real-time quantitative RT-PCR in ALS tissues. GEMsdecreased in both TDP-43-depleted HeLa cells and spinal motor neurons in ALSpatients. Levels of several U snRNAs decreased in TDP-43-depleted SH-SY5Y andU87MG cells. The level of U12 snRNA was decreased in tissues affected by ALS butnot in tissues unaffected by ALS. These findings suggest that loss of TDP-43 functiondecreases the number of GEMs, which is followed by a disturbance of pre-mRNAsplicing by the U11/U12 spliceosome in tissues affected by ALS.

    researchmap

  • Analysis of TDP-43 functions and modeling for ALS using conditional knockout mice

    Grant number:22590925

    2010 - 2012

    System name:Grants-in-Aid for Scientific Research(基盤研究(C))

    Research category:基盤研究(C)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Toshiya SATO, Onodera OSAMU, Hirokawa SACHIKO

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    To investigate the physiological functions of TAR DNA-binding protein 43 kDa (TDP-43), we established TDP-43 conditional knockout (cKO) mice and evaluated the validity of disease models for amyotrophic lateral sclerosis (ALS). As a result of the autoregulation, TDP-43 mRNAs were recovered to wild type levels in various tissues of heterozygous TDP-43 KO (Tardbp^+/-) mice. This recovery would prevent from the emergence of abnormal phenotypes. On the other hand, TDP-43 mRNA level in unfertilized oocytes obtained from heterozygous mice was reduced by half. This haploinsufficiency would account for the delay of early embryonic development. Because homozygous (Tardbp^-/-) mice died by early post-implantation stage, we established neuron-specific KO (Tardbp^flox/flox、NSE-Cre^+) mice using NSE39-Cre mice. Neuron-specific KO mice showed sever neurological phenotypes with a median survival of 20 days. Pathologically, chromatolysis and abnormal-shaped mitochondria, characteristic features of ALS, were observed in lumbar motor neurons.

    researchmap

  • Mathematic statistical analyses of relationship between severity of neurological symptom and MRI measurements of white matter injury

    Grant number:22591318

    2010 - 2012

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    TERAJIMA Kenshi, AKAZAWA Kouhei, ONODERA Osamu

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    The purposes of this project are: 1) to develop a computer-based method of characterizing white matter injury; 2) to develop a method of analyzing white matter injury by using modern MR techniques; and 3) to integrate these two methods mathematically and statistically. This report overviews the results of this project as follows. Firstly, we proposed a mathematic statistical model of growth cone behavior that employs multiple sensors designed for simulating the signal transduction system. Secondly, we found biomarkers of disease severity in multiple system atrophy of cerebellar type (MSA-C) by imaging disease specific regions using proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 T system. Finally, we analyzed relationship between severity of clinical symptoms of a patient with white matter injury and MRI measurements of the lesions.

    researchmap

  • 天然変性タンパク質の機能解析によるALSの病態機序の解明

    Grant number:22113506

    2010 - 2011

    System name:科学研究費補助金(新学術領域研究(研究領域提案型))

    Research category:新学術領域研究(研究領域提案型)

    Awarding organization:文部科学省

    小野寺 理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5980000 ( Direct Cost: \4600000 、 Indirect Cost:\1380000 )

    ALSの原因遺伝子としてfused in sarcoma/translated in liposarcoma(FUS/TLS)やTDP-43が見いだされた.これらの遺伝子の発見は,ALS研究において新たな病態機序を提唱するに至った.驚くことに,何れの遺伝子もRNA結合能を持ち,RNA代謝において機能すると考えられている.さらに何れの蛋白質も,天然変性蛋白領域を高頻度で含んでいること,さらにその変性領域に変異が集中している.特にTDP-43は現在まで30種類以上の変異が報告されているが,そのほとんどすべてがC末の本来的に不規則な領域に集中している.またC末は単独では凝集体を形成しやすい.このため,これらの蛋白質の天然変性領域の機能を明らかにすることが,本症の病態解明において重要である.しかし,この天然変性蛋白領域の機能については全く明らかとなっていない.我々はTDP-43には新しい多数のスプライシングバリアントが存在し,このスプライシングバリアントの多くが天然変性蛋白領域に関係していることを見いだした.この事実からTDP-43の天然変性蛋白領域はTDP-43の安定性に深く寄与しており,これを欠くTDP-43のスプライシングバリアントは凝集性を増すことを見いだした.この発見により,TDP-43の天然変性蛋白領域の本症への関与が示された.

    researchmap

  • 遺伝性脳小血管病の病態機序の解明と治療法の開発

    2010 - 2011

    System name:平成22年度難治性疾患克服研究事業(新規)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\10700000 ( Direct Cost: \5350000 、 Indirect Cost:\4500000 )

    researchmap

  • Identification for serum biomarker for ALS associated with the function of TDP-43

    Grant number:22659169

    2010 - 2011

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    ONODERA Osamu

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3190000 ( Direct Cost: \2800000 、 Indirect Cost:\390000 )

    Amyotrophic lateral sclerosis(ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons. In the ALS motor neurons, TAR DNA-binding protein of 43 kDa(TDP-43) is dislocated from the nucleus to cytoplasm and forms inclusions, suggesting that loss of a nuclear function of TDP-43 may underlie the pathogenesis of ALS. TDP-43 functions in RNA metabolism include regulation of transcription, mRNA stability, and alternative splicing of pre-mRNA. However, a function of TDP-43 in tissue affected with ALS has not been elucidated. We sought to identify the molecular indicators reflecting on a TDP-43 function. Using exon array analysis, we observed a remarkable alteration of splicing in several genes as a result of the depletion of TDP-43 expression in two types of cultured cells. In the cells treated with TDP-43 siRNA, wild-type splicing variants decreased and transcripts lacking some exons increased. The RNA binding ability of TDP-43 was necessary for inclusion and exclusion of these exons. Moreover, we found an increment of splicing varinats in motor cortex, spinal cord and spinal motor neurons collected by laser microdissection with ALS. Our results suggest a loss of TDP-43 function in tissues affected with ALS, supporting the hypothesis that a loss of function of TDP-43 underlies the pathogenesis of ALS.

    researchmap

  • 遺伝性脳小血管病の病態機序の解明と治療法の開発

    2009

    System name:難治性疾患克服研究事業(二次公募)

    Awarding organization:厚生労働科学研究費補助金

    小野寺理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17400000 ( Direct Cost: \8700000 、 Indirect Cost:\4000000 )

    researchmap

  • L-plastin ; the possibility as a surrogate marker of polyglutamine diseases.

    Grant number:20500322

    2008 - 2010

    System name:Grants-in-Aid for Scientific Research(基盤研究(C))

    Research category:基盤研究(C)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Yasuko TOYOSHIMA, Osamu ONODERA, Hitoshi TAKAHASHI

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    L-plastin is a protein involved in actin filament organization and endocytotic processes. We found that the expression of L-plastin increased in the brains of polyglutamine diseases. We examined the relations about the L-plastin and polyglutamine. L-plastin was shown to come to have much expression in the progress of several weeks in vitro. It is thought that L-plastin may be related with a phenomenon to need time before polyglutamine disease develops.

    researchmap

  • Amyotrophic lateral sclerosis and TDP-43 : elucidation of the entire neuropathological picture and molecular pathomechanism

    Grant number:20240037

    2008 - 2010

    System name:Grants-in-Aid for Scientific Research(基盤研究(A))

    Research category:基盤研究(A)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Hitoshi TAKAHASHI, 譚 春鳳, Yasuko TOYOSHIMA, Osamu ONODERA, ChenーFeng TAN, Akiyoshi KAKITA, Kenji SAKIMURA, Ryozo KUWANO, Minesuke YOKOYAMA

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\37440000 ( Direct Cost: \28800000 、 Indirect Cost:\8640000 )

    We examined clinicopathologically and immunohistochemically a large series of sporadic amyotrophic lateral sclerosis (SALS) cases, including those having long disease durations with artificial respiratory support. In each case, various brain regions were immunostained with an antibody against TDP-43, showing occurrence of TDP-43-positive neuronal (NCIs) and glial cytoplasmic inclusions in many regions, including the lower motor neuron nuclei. The results obtained indicate that SALS is a multisystem neuro-glial proteinopathy of TDP-43 and can show two pathological phenotypes (types 1 and 2 ; type 2 can be distinguished from type 1 by the presence of TDP-43-positive NCIs in the frontotemoral cortex, hippocampal formation, neostriatum and substantia nigra). We also generated a transgenic TDP-43 KO mouse model for further biochemical and molecular analyses on the pathomechanisms underlying SALS. The several data obtained strongly suggest that our next target is "splicing abnormalities of TDP-43".

    researchmap

  • 核内小体機能不全による非翻訳リボ核酸の異常による運動神経細胞死の研究

    Grant number:20659139

    2008 - 2009

    System name:科学研究費補助金(萌芽研究, 挑戦的萌芽研究)

    Research category:萌芽研究, 挑戦的萌芽研究

    Awarding organization:文部科学省

    小野寺 理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3200000 ( Direct Cost: \3200000 )

    筋萎縮性側索硬化症(ALS)の病態機序は不明であり,有効な治療法はない.治療法開発には運動神経細胞死の病態機序の解明が必須である.ALS患者の神経細胞にはTDP-43の異常蓄積が認められる.TDP-43は核蛋白であり,他の核内小体であるCajal小体,Gemと共局在する.興味深いことに,これらの核内小体には,遺伝性運動神経細胞死を来たす原因遺伝子であるSMNとアプラタキシンも局在する.このことから運動神経細胞死において核内小体が重要な役割を果たすと考え,これを検証する.具体的には,神経細胞死においてCajal小体を始めとする核内小体の挙動を検討する.さらに,核内小体が,その成熟に関与する非翻訳RNA(ncRNA)の量的変化を解析する.対象は孤発性ALS,TDP-43変異をもつ家族性ALS,TDP-43欠損マウス,変異TDP-43導入マウス,アプラタキシン欠損マウスとする.ALS患者において,Cajal小体の数,ncRNAの解析を行い,それらが有意差をもってALS群の患者運動神経細胞,神経組織で低下していることを示した.

    researchmap

  • Impairment of quality control system for nucleic acids and neurodegenerative disorders.

    Grant number:19390236

    2007 - 2009

    System name:Grants-in-Aid for Scientific Research(基盤研究(B))

    Research category:基盤研究(B)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Osamu ONODERA, Toshiaki TAKAHASHI, Tetsutaro OZAWA, Yasuko TOYOSHIMA

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\15990000 ( Direct Cost: \12300000 、 Indirect Cost:\3690000 )

    researchmap

  • The spectrum of pathological involvement in Japanese multiple system atrophy

    Grant number:19590983

    2007 - 2008

    System name:Grants-in-Aid for Scientific Research(基盤研究(C))

    Research category:基盤研究(C)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Tetsutaro OZAWA, Hitoshi TAKAHASHI, Osamu ONODERA

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\1430000 ( Direct Cost: \1100000 、 Indirect Cost:\330000 )

    researchmap

  • Elucidation of molecular mechanisms of neurological diseases based on genome analysis

    Grant number:17019006

    2005 - 2009

    System name:Grants-in-Aid for Scientific Research(特定領域研究)

    Research category:特定領域研究

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Shoji TSUJI, 後藤 順, 高橋 祐二, 百瀬 義雄, Osamu ONODERA, Shigeo MURAYAMA, Jun GOTO, Yuji TAKAHASHI

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\781600000 ( Direct Cost: \781600000 )

    This study has focused on elucidation of molecular mechanisms of neurological diseases based on genome analysis, and, eventually, to develop disease-modifying therapy for neurological diseases. This study focused on the broad range of neurological diseases ranging from single gene diseases to polygenic diseases. To facilitate the linkage study for familial diseases, a high throughput linkage analysis system (SNP HiTLink) employing SNP microarrays has been developed and applied for many diseases. Regarding single gene diseases, we have discovered the causative gene for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). For sporadic diseases, we have identified a strong disease suseceptibility gene for Parkinson disease. The result emphasizes the paradigm shift from common disease-common variants hypothesis to common disease-multiple rare variants hypothesis.

    researchmap

  • Atherapeutic approach to polyglutamine diseases by the activation of cellularproteolyticpathways

    Grant number:17300109

    2005 - 2007

    System name:Grants-in-Aid for Scientific Research(基盤研究(B))

    Research category:基盤研究(B)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Mitsunori YAMADA, Osamu ONODERA, Hitoshi TAKAHASHI

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\11920000 ( Direct Cost: \10900000 、 Indirect Cost:\1020000 )

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. In the studies of DRPLA, we have demonstrated that diffuse accumulation of mutant atrophi-1, DRPLA causative protein, in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions, was the predominant pathologic condition and involved a wide range of central nervous system regions far beyond the systems previously reported to be affected. The novel lesion distribution varies depending on the expanded sizes of CAG repeats, and may be responsible for a variety of clinical features, such as dementia and epilepsy in DRPLA. These pathologic conditions suggest that the degradation of accumulated mutant proteins may serve as a target for a new therapeutic approach to polyglutamine diseases. In the human DRPLA brains, we found that accumulated mutant atrophin-1 was decreased selectively in the hypertrophic neurons in the inferior olivary hypertrophy. Experimentally induced hypertrophy of the inferior olive in DRPLA mouse models also showed the decrease or disappearance of accumulated mutant proteins. Expression profile analyses demonstrated hypertrophy-dependent up- and down-regulations of genes. EttanTM DIGE (2-D Fluorescence Difference Gel Electrophoresis) analyses detected several molecules that were specifically induced in the hypertrophic olivary neurons.

    researchmap

  • 内在性相補鎖RNAによる遺伝子発現調節機構に注目したシヌクレイン関連蛋白の解析

    Grant number:16659229

    2004 - 2005

    System name:科学研究費補助金(萌芽研究)

    Research category:萌芽研究

    Awarding organization:文部科学省

    小野寺 理, 柿田 明美

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2800000 ( Direct Cost: \2800000 )

    多系統萎縮症(MSA)は本邦に一万人程の罹患患者がいると考えられるが,その原因および有効な治療戦略は提案されていない。本症はGlial Cytoplasmic Inclusion(GCI)というα-synucleinからなる神経細胞内封入体を特徴とする。α-synucleinが主成分である神経細胞内封入体にはパーキンソン病で認められるLewy小体があるがGCIではsynphilin-1の存在が特徴的である。このことからsynphilin-1とシヌクレイン関連蛋白の関与が疑われている(Acta Neuropathol 2002 103)。我々はこれらの遺伝子の特定のハプロタイプが疾患感受性を規定すると考え,synphilin-1を含むシヌクレイン関連遺伝子のMSA患者群におけるSNPsとEM法を用いたハプロタイプ解析を行った。しかし,これら遺伝子の翻訳領域のハプロタイプ解析では疾患群と対照群で差を見いだすことはできなかった。今年度はsynphilin-1近傍のマーカーにて,有意差を認める領域を同定し,本領域の一塩基置換が,疾患の発症との関与を示した.

    researchmap

  • New polyglutamine diseases : from the neuropathologies to the identification of genes responsible for the diseases

    Grant number:16390104

    2004 - 2005

    System name:Grants-in-Aid for Scientific Research(基盤研究(B))

    Research category:基盤研究(B)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Hitoshi TAKAHASHI, Yasuko TOYOSHIMA, Mitsunori YAMADA, Osamu ONODERA

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\6000000 ( Direct Cost: \6000000 )

    We have studied three patients with pathologically different hereditary spinocerebellar ataxia characterized by 1C2-immunopositive intranuclear inclusions in the affected CNS neurons, namely, polyglutamine diseases. We have also tried to identify the gene responsible for each hereditary disease.(1)We have described a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum ; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.(2)In one of the other two cases, immunoblotting analyses with a monoclonal antibody specific for expanded polyglutamine stretches (1C2) revealed the presence of immunopositive proteins. Furthermore, we identified multiple spots, one of which might be the disease-related protein, using two-dimensional electrophoresis and two-dimensional immunoblotting methods. Further studies are needed to identify the gene responsible for the disease.(3)In the final case, we are trying the same methods to identify the disease-related protein and the causative gene abnormality.

    researchmap

  • Transcriptional disturbance and Neurodegeneration.

    Grant number:15390272

    2003 - 2004

    System name:Grants-in-Aid for Scientific Research(基盤研究(B))

    Research category:基盤研究(B)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Osamu ONODERA, Mutsuo OYAKE, Shuichi IGARASHI

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\14900000 ( Direct Cost: \14900000 )

    By using isogenic stable inducible cell lines, we showed the polyglutamine stretch suppressed the CRE dependent transcription in their early stage. However their repressive effects were not so dramatically different in different cell lines which have different length of polyglutamine stretch. Furthermore its repressive effect is not affected the existence of aggregate formation. Taken together CRE mediated transcriptional repression was not a pathogenic for polyglutamine disease. By using these cell lines, we showed the expanded polyglutamine stretch retained in cell, speciously in nucleus by length dependent manner. The UPS, one of the main systems to degradate unfolded proteins in cells, was not suppressed in these cell lines. Therefore we speculated that polyglutamine stretch itself has resistance to degradation, thus accumulate in nucleus.The other neurodegenerative disorders, early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH/AOA1) is caused by mutation of APTX. We show the APTX binds to X-ray repair cross-complementing group 1 protein, which is the scaffold protein for base excision repair (BER) machinery in single strand DNA break repair (SSBR), and made complex with poly (ADP-ribose) polymerase. These findings support the idea that APTX might take an important role in SSBR system.

    researchmap

  • Identified the causative gene for EAOH end elucidation the molecular mechanisms of neurodegeneration in EAOH

    Grant number:14207029

    2002 - 2003

    System name:Grants-in-Aid for Scientific Research(基盤研究(A))

    Research category:基盤研究(A)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Shoji TSUJI, Mutsuo OYAKE, Osamu ONODERA, Jun GOTO

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\39650000 ( Direct Cost: \30500000 、 Indirect Cost:\9150000 )

    We have previously identified the causative gene for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), an autosomal recessive neurodegenerative disease. We named the causative gene "aprataxin". This study was aimed to elucidate the molecular mechanisms of neurodegeneration in EAOH and, furthermore, to establish the therapeutic strategies for this diseases. In previous studies we showed that there are two major isoforms of aprataxin mRNA, of which we demonstrated that long form aprataxin is the component essential for its physiological function. Furthermore, we identified that aprataxin interacts with XRCC1 (X-ray repair cross complementing group 1) based on yeast two hybrid assay as well as im nuno coprecipitation experiments, raising the possibility that aprataxin has a physiological function in single strand DNA break repair (SSBR). In vitro reconstitution experiments of SSBR demonstrated that aprataxin contains 5'-phophatase as well as 3'-phophatase activities.Taken together these findings suggest that aprataxin is a new member of molecules involved in SSBR.

    researchmap

  • Research for the role of dystrophic neurites in neuronal cell dysfunction of Polyglutamine disease

    Grant number:13670635

    2001 - 2002

    System name:Grants-in-Aid for Scientific Research(基盤研究(C))

    Research category:基盤研究(C)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Osamu ONODERA, Mutsuo OYAKE

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3600000 ( Direct Cost: \3600000 )

    To understand the pathogenetic mechanisms underlying polyglutamine diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA).We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with γ-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on microtubules to the MTOC, where they remain as distinct "aggresomes".Then we have established several stable cell lines, which expressed polyQ stretches under control of tetracycline. In these cell lines, the integration sites are identical so we could exclude the effect of a chromosomal localization of integrated cDNA. Using these stable cell lines we have seen the turnover rates of polyQ stretch is different.In future we will analysis the effects of the difference of the fate of polyQ stretch by their length on neuronal cell function, specially their axonal transport system.

    researchmap

  • Molecular mechanisms of neurodegeneration

    Grant number:12210008

    2000 - 2004

    System name:Grants-in-Aid for Scientific Research(特定領域研究(C), 特定領域研究)

    Research category:特定領域研究(C), 特定領域研究

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Shoji TSUJI, 小宅 睦郎, 成瀬 聡, Osamu ONODERA, 清水 潤, Jun GOTO, Yuji TAKAHASHI

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\244200000 ( Direct Cost: \244200000 )

    To date, 9 polyglutamine diseases including dentatorubral-pallidoluysian atrophy (DRPLA) have been identified to be caused by abnormal expansion of CAG repeats coding for polyglutamine stretches. To elucidate the molecular mechanisms of neurodegeneration in polyglutamine diseases, we first attempted to create mouse models that closely replicate pathophysiologic processes in human brains. To accomplish this aim, we tried to create transgenic mice carrying a full-length mutant human DRPLA gene as a single copy gene. The Q129 mouse carrying a largely expanded CAG repeats (129) showed strong neurological phenotypes including ataxia, myoclonus and epilepsy. Based on detailed neuropathological analyses, we found that neuronal loss was not detected despite the strong phenotypes, suggesting that neuronal death is not the essential processes in neurodegeneration. We furthermore found that intranuclear accumulation of mutant DRPLA proteins is the essential neuropathological findings. This observation raises the possibility that nuclear dysfunction underlies the neurodegeneration in polyglutamine diseases. Based on cell culture systems, we demonstrated that CREB-dependent transcriptional activation is severely suppressed employing a reporter system. We further demonstrated activation of endogenous c-fos transcription is also strongly suppressed by expanded polyglutamine stretches. To further elucidate the mechanisms of transcriptional dysregulation in polyglutamine diseases, we have conducted detailed expression profiling analyses using Q76, Q113 and Q129, carrying a full-length mutant human DRPLA gene as a single copy gene with various lengths of expanded CAG repeats (76, 113 and 129 repeat units). We found that substantial number of genes were suppressed in time-dependent and repeat length-dependent manners. Among the down-regulated genes, many cAMP-responsive genes (c-fos and EGR1) are included Taken together, we have demonstrated that suppression of CREB-dependent transcriptional activation is strongly suppressed by expanded polyglutamine stretches and restoration of such suppression is the target for developing therapeutic approaches for polyglutamine diseases.

    researchmap

  • Elucidation of molecular mechanisms of neurodegenerative diseases caused by expansion of CAG repeats

    Grant number:12307014

    2000 - 2001

    System name:Grants-in-Aid for Scientific Research(基盤研究(A))

    Research category:基盤研究(A)

    Awarding organization:Ministry of Education, Culture, Sports, Science and Technology

    Shoji TSUJI, Osamu ONODERA, Hisashi KOBAYASHI

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid)  Grant type:Competitive

    Grant amount:\34980000 ( Direct Cost: \31200000 、 Indirect Cost:\3780000 )

    This study was aimed to elucidate molecular mechanisms ofheurodegetterative diseases caused by expansion of CAG repeats. To accomplish this aim, two strategies! have been employed; 1. Molecular cloning of CAG repeat-containing cDNAs expressed in human brains as the candidate genes for hereditary neurodegenerative diseases, and 2. Elucidation of mechanisms of neurodegeherati6n : caused by expahded; CAG repeats coding for polyglutarnine stretches. As the former approach, we screened human brain cDNA libraries using (CAG)10 or (CAG)20 oligbnucleotide probes. Excluding overlapping clones, we have identified 92 independent cDNA clones as the CAG repeat-containing CDNA clones. Among the 92 clones, we selected 41 clones as the CDNA clones carrying > 10 CAG repeats. These cDNA clones are beihg screeried as the candfdate genes for hereditary neurddegenerative disease. As the latter approach, we focused our study to elucidate the mechanisms of nuclear dysfunctions as a result of nuclear transport and intranuclear accumulation of mutant protein carrying expanded polyglutamine stretches. We performed expression pro filing of Q129 mice catfying a full-length mutant DRPEA gene carrying a largely expanded GAG repeat (129 repeat units) that have been developed in our laboratory. Detailed expression pro filing analysis revealed 78 down-regulated genes and 16 up-regulated genes. The alteration of expression levels is observed as a time-dependent manner. Many cAMP-resporisive genes were included in the dpwh-regulated genes, confirming our hypothesis that CREB-dependent transcriptional activation is suppressed by expanded polyglutamine stretches.

    researchmap

  • ポリグルタミン病における凝集体と神経細胞死の関連の解明と凝集体阻害剤の探求

    Grant number:11770325

    1999 - 2000

    System name:科学研究費補助金(奨励研究(A))

    Research category:奨励研究(A)

    Awarding organization:文部科学省

    小野寺 理

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2100000 ( Direct Cost: \2100000 )

    遺伝性脊髄小脳変性症の内、現在8疾患がCAG繰り返し配列によりコードされる増大したポリグルタミン鎖により引き起こされることが明らかとなっている。これらの疾患ではCAGリピート数の増加に伴い発症年齢が若年化する傾向が知られているが、同じCAGリピート数でも疾患間で発症年齢が異なる。この理由については明らかにされていない。昨年度、我々はポリグルタミン鎖周辺のアミノ酸配列が増大ポリグルタミン鎖の凝集体形成能に影響を与える可能性を考え、truncated ataxin2,huntingtin,DRPLAP,ataxin3においてその凝集体形成能の違いと,凝集体形成能に及ぼす周辺アミノ酸配列の影響,及び個々のポリグルタミン病との関連を検討しCAGリピートの長さ依存性に34から36リピート間に閾値を持って凝集体形成能の増加を認めること、56CAGリピートを共通に含むtruncated ataxin2,huntingtin,DRPLAP,ataxin3の発現ではtruncated ataxin2及びhuntingtinがtruncated DRPLAP及びataxin3に比べ高率な凝集体形成能を示し、ヒトでの疾患重症度との傾向と相関することを報告した。今年度は同蛋白の凝集体形成能を変異を導入することにより変化させることができるか否かをtrancated ataxin2の変異導入体を用い検討した。凝集体形成能には周辺アミノ酸配列の疎水性が大きく関与していることが疑われたため,疎水性アミノ酸を親水性アミノ酸に変えた変異体を作成し、その凝集体形成能を検討した。その結果親水性アミノ酸導入変異体では凝集体形成が強く抑制された。この結果は増大ポリグルタミン鎖の凝集体形成能が僅かなアミノ酸変異により変化得る可能性を示している.

    researchmap

  • Neurodegenerative diseases

      More details

    Grant type:Competitive

    researchmap

▶ display all

 

Teaching Experience

  • 医学序説 I

    2021
    Institution name:新潟大学

  • 臓器別講義・演習Ⅰ

    2020
    Institution name:新潟大学

  • 臨床医学講義(集中)

    2020
    Institution name:新潟大学

  • 医学序説 II

    2020
    Institution name:新潟大学

  • 脳神経系

    2017
    Institution name:新潟大学

  • 医科学研究特論

    2015
    Institution name:新潟大学

  • 医科学総合演習

    2014
    Institution name:新潟大学

  • 神経内科学

    2008
    -
    2015
    Institution name:新潟大学

▶ display all