研究者詳細 - 小野寺　理

論文 - 小野寺　理

分割表示 492 件中 341 - 360 件目／全件表示 >>

Reliability of the Japanese version of the scale for the assessment and rating of ataxia (SARA) 査読

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年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）

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.

Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice 査読

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

A patient with anti-aquaporin 4 antibody who presented with recurrent hypersomnia, reduced orexin (hypocretin) level, and symmetrical hypothalamic lesions 査読

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology 査読

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年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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 (<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

Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology 査読

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年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 (< 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

Molecular mechanism for spinocerebellar ataxias 査読

Osamu Onodera

Clinical Neurology 49 ( 11 ) 750 - 752 2009年

記述言語：日本語掲載種別：研究論文（国際会議プロシーディングス）

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

Molecular mechanism for spinocerebellar ataxias 査読

Osamu Onodera

Clinical Neurology 49 ( 1 ) 1 - 8 2009年

記述言語：日本語出版者・発行元：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

Electroclinical features of epilepsy in patients with juvenile type dentatorubral-pallidoluysian atrophy 査読

Kiyoshi Egawa, Yukitoshi Takahashi, Yuko Kubota, Hideki Kubota, Yushi Inoue, Takeki Fujiwara, Osamu Onodera

EPILEPSIA 49 ( 12 ) 2041 - 2049 2008年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 < 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

Cardiac sympathetic denervation in Parkinson's disease linked to SNCA duplication 査読

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年11月

Development of a high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis 査読

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年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Marinesco-Sjögren syndrome with atrophy of the brain stem tegmentum and dysplastic cytoarchitecture in the cerebral cortex. 査読

Sakai K, Tada M, Yonemochi Y, Nakajima T, Onodera O, Takahashi H, Kakita A

Neuropathology : official journal of the Japanese Society of Neuropathology 28 ( 5 ) 541 - 546 2008年10月

Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population 査読

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families 査読

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions 査読

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Sporadic ataxias in Japan - a population-based epidemiological study 査読

Shoji Tsuji, Osamu Onodera, Jun Goto, Masatoyo Nishizawa

CEREBELLUM 7 ( 2 ) 189 - 197 2008年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia 査読

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Mutational analysis in early-onset familial dementia in the Japanese population 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

TDP-43 mutation in familial amyotrophic lateral sclerosis 査読

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年

Contribution of APP duplication as a cause in a cohort of Japanese Alzheimer disease patients 査読

Kensaku Kasuga, Atsushi Shiga, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa, Takeshi Ikeuchi

NEUROSCIENCE RESEARCH 61 S264 - S264 2008年

Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families 査読

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年

　前のページ - 次のページ　

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25