研究者詳細 - 小野寺　理

論文 - 小野寺　理

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USP10 inhibits aberrant cytoplasmic aggregation of TDP-43 by promoting stress granule clearance. 国際誌

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年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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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年1月

Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy. 国際誌

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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Neuronal Intranuclear Inclusion Disease Presenting with Voice Tremor 国際誌

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年12月

Parkinson's disease and parkinsonism: Clinicopathological discrepancies on diagnosis in three patients. 国際誌

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年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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[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年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

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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年11月

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年10月

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年10月

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年10月

Do patients with multiple system atrophy have decreased nocturnal urinary concentration? 国際誌

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

Clinical autonomic research : official journal of the Clinical Autonomic Research Society 2021年9月

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年9月

Hemiplegic-type ALS: clinicopathological features of two autopsied patients. 国際誌

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年9月

[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年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

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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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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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年9月

[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年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

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Predictive markers based on transcriptome modules for vinorelbine-based adjuvant chemotherapy for lung adenocarcinoma patients. 国際誌

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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Immunological abnormalities in patients with early-onset ataxia with ocular motor apraxia and hypoalbuminemia. 国際誌

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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Pyloric-gland metaplasia may be an origin of cancer and intestinal metaplasia with possible CDX2 expression. 国際誌

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

Gastroenterology report 9 ( 4 ) 370 - 373 2021年8月

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