研究者総覧

松浦 徹 (マツウラ トオル)

  • 内科学講座(神経内科学部門) 教授
Last Updated :2021/12/07

研究者情報

学位

  • 医学博士(北海道大学)

ホームページURL

J-Global ID

研究キーワード

  • 遺伝子   遺伝学   神経科学   脳神経疾患   脳・神経   RNA   スプライシング異常   脊髄小脳失調症10型   筋強直性ジストロフィー   非翻訳領域リピート病   

研究分野

  • ライフサイエンス / 神経内科学
  • ライフサイエンス / 医化学
  • ライフサイエンス / 分子生物学

経歴

  • 2013年 - 現在  自治医科大学医学部内科学講座神経内科学部門教授
  • 2009年  岡山大学院医歯薬学総合研究科脳神経内科学准教授
  • 2005年  名古屋大学大学院医学系研究科・神経遺伝情報学准教授Graduate School of Medicine
  • 2002年  Assistant Professor, Molecular and Human Genetics, Baylor College of Medicine
  • 2000年  Instructor, Neurology, Baylor College of Medicine
  • 1998年  Postdoctoral Fellow, Neurology, Baylor College of Medicine
  • 1997年  北海道大学医学部附属病院 神経内科医員
  • 1988年  北海道職員

学歴

  • 1982年 - 1988年   自治医科大学   医学部

所属学協会

  • The Society for Neuroscience (SFN)   American Society of Human Genetics (ASHG)   日本分子生物学会   日本内科学会   日本頭痛学会   日本認知症学会   

研究活動情報

論文

  • Different impacts on brain function depending on the mode of delivery.
    Ikeda K, OnimaruH, Matsuura T, Kawakami K
    Brain Research 1720 146289  2019年10月 [査読有り][通常論文]
  • PLEKHG5遺伝子の複合ヘテロ塩基置換を認めた進行性運動感覚ニューロパチーの孤発例
    嶋崎 晴雄, 古谷 浩平, 横瀬 美里, 鈴木 雅之, 金 蓮姫, 小澤 忠嗣, 松薗 構佑, 益子 貴史, 小出 玲爾, 松浦 徹, 藤本 茂
    臨床神経学 58 Suppl. S270 - S270 (一社)日本神経学会 2018年12月 [査読有り][通常論文]
  • 嶋崎 晴雄, 益子 貴史, 古谷 浩平, 横瀬 美里, 鈴木 雅之, 金 蓮姫, 小澤 忠嗣, 松薗 構佑, 小出 玲爾, 松浦 徹, 藤本 茂
    神経治療学 35 6 S240 - S240 (一社)日本神経治療学会 2018年11月 [査読有り][通常論文]
  • Misato Yokose, Kohei Furuya, Masayuki Suzuki, Tadashi Ozawa, Younhee Kim, Kumiko Miura, Kosuke Matsuzono, Takafumi Mashiko, Mari Tada, Reiji Koide, Haruo Shimazaki, Tohru Matsuura, Shigeru Fujimoto
    Neuro-ophthalmology (Aeolus Press) 42 5 309 - 311 2018年10月 [査読有り][通常論文]
     
    Vertical gaze palsy is rarely a neurological symptom, although it has been observed in some cases. Here, we report the case of a patient presenting with complete upward and downward gaze palsy. In this case, a small lesion in the left rostral midbrain was observed on diffusion-weighted magnetic resonance (MR) images, and the lesion was considered to cause the ocular symptom. We consider that vertical gaze palsy is an important clue to an accurate topical diagnosis of a brain lesion.
  • Kosuke Matsuzono, Naoto Arai, Masayuki Suzuki, Younhee Kim, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Tohru Matsuura, Shigeru Fujimoto
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 6 e110-e112 - e112 2018年06月 [査読有り][通常論文]
     
    Although foam sclerotherapy to varicose veins is now a popular treatment because of its high efficacy and safety, some neurologic complications have recently been reported. Presently, the effectiveness and safety of intravenous recombinant tissue-type plasminogen activator therapy to stroke following foam sclerotherapy remain unclear. Here, we report the case of a 68-year-old woman whose ischemic symptoms following foam sclerotherapy were treated by intravenous recombinant tissue-type plasminogen activator. After she was admitted, the venous thrombosis in her right soleus vein and a patent foramen ovale causing the right-to-left shunt were revealed. Thus, we diagnosed the ischemic symptoms were due to paradoxical embolism following foam sclerotherapy. After intravenous recombinant tissue-type plasminogen activator therapy, there was no complication and the outcome was good. Our case suggests the effectiveness and the safety of intravenous recombinant tissue-type plasminogen activator therapy to paradoxical embolism following foam sclerotherapy.
  • Pure motor isolated finger palsyを呈した脳梗塞の70歳男性例
    平山 果歩, 横瀬 美里, 小澤 忠嗣, 金 蓮姫, 松薗 構佑, 益子 貴史, 小出 玲爾, 嶋崎 晴雄, 松浦 徹, 藤本 茂
    臨床神経学 58 4 249 - 249 (一社)日本神経学会 2018年04月 [査読有り][通常論文]
  • 下肢静脈瘤硬化療法に続発した奇異性脳塞栓症に対してrt-PA治療を施行した68歳女性例
    鈴木 雅之, 松薗 構佑, 新井 直人, 金 蓮姫, 小澤 忠嗣, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 松浦 徹, 藤本 茂
    臨床神経学 58 1 53 - 53 (一社)日本神経学会 2018年01月 [査読有り][通常論文]
  • Ocular flutterが再発の初期徴候であったびまん性大細胞型B細胞性リンパ腫の1例
    黒田 百恵, 古谷 浩平, 金 蓮姫, 小澤 忠嗣, 松薗 構佑, 益子 貴史, 小出 玲爾, 松浦 徹, 翁 家国, 藤本 茂
    日本内科学会関東地方会 638回 40 - 40 日本内科学会-関東地方会 2017年12月 [査読有り][通常論文]
  • 脳虚血症状の出現から2年以内の経過で両側内頸動脈閉塞に至った甲状腺機能亢進症合併類もやもや病の一例
    鈴木 雅之, 松薗 構佑, 金 蓮姫, 小澤 忠嗣, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 松浦 徹, 藤本 茂
    脳循環代謝 29 1 192 - 192 (一社)日本脳循環代謝学会 2017年11月 [査読有り][通常論文]
  • Takafumi Mashiko, Eiji Sakashita, Katsumi Kasashima, Kaoru Tominaga, Kenji Kuroiwa, Yasuyuki Nozaki, Tohru Matsuura, Toshiro Hamamoto, Hitoshi Endo
    JOURNAL OF BIOLOGICAL CHEMISTRY 291 29 14996 - + 2016年07月 [査読有り][通常論文]
     
    Cytoplasmic protein aggregates are one of the pathological hallmarks of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FT LD). Several RNA-binding proteins have been identified as components of inclusion bodies. Developmentally regulated RNA-binding protein 1 (Drbl)/RNA-binding motif protein 45 is an RNA-binding protein that was recently described as a component in ALS- and FTLD-related inclusion bodies. However, the molecular mechanism underlying cytoplasmic Drbl aggregation remains unclear. Here, using an in vitro cellular model, we demonstrated that Drbl co-localizes with cytoplasmic aggregates mediated by TAR DNA-binding protein 43, a major component of ALS and FTLD-related inclusion bodies. We also defined the domains involved in the subcellular localization of Drbl to clarify the role of Drbl in the formation of cytoplasmic aggregates in ALS and FTLD. Drbl predominantly localized in the nucleus via a classical nuclear localization signal in its carboxyl terminus and is a shuttling protein between the nucleus and cytoplasm. Furthermore, we identify a double leucine motif serving as a nuclear export signal. The Drbl mutant, presenting mutations in both nuclear localization signal and nuclear export signal, is prone to aggregate in the cytoplasm. The mutant Drb 1-induced cytoplasmic aggregates not only recruit TAR DNA-binding protein 43 but also decrease the mitochondrial membrane potential. Taken together, these results indicate that perturbation of Drbl nuclear cytoplasmic trafficking induces toxic cytoplasmic aggregates, suggesting that mislocalization of Drbl is involved in the cause of cytotoxicity in neuronal cells.
  • Guiying Chen, Akio Masuda, Hiroyuki Konishi, Bisei Ohkawara, Mikako Ito, Masanobu Kinoshita, Hiroshi Kiyama, Tohru Matsuura, Kinji Ohno
    SCIENTIFIC REPORTS 6 25317  2016年04月 [査読有り][通常論文]
     
    Myotonic dystrophy type 1 (DM1) is caused by abnormal expansion of CTG repeats in the 3' untranslated region of the DMPK gene. Expanded CTG repeats are transcribed into RNA and make an aggregate with a splicing regulator, MBNL1, in the nucleus, which is called the nuclear foci. The nuclear foci sequestrates and downregulates availability of MBNL1. Symptomatic treatments are available for DM1, but no rational therapy is available. In this study, we found that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone (PBZ), upregulated the expression of MBNL1 in C2C12 myoblasts as well as in the HSA(LR) mouse model for DM1. In the DM1 mice model, PBZ ameliorated aberrant splicing of Clcn1, Nfix, and Rpn2. PBZ increased expression of skeletal muscle chloride channel, decreased abnormal central nuclei of muscle fibers, and improved wheel-running activity in HSALR mice. We found that the effect of PBZ was conferred by two distinct mechanisms. First, PBZ suppressed methylation of an enhancer region in Mbnl1 intron 1, and enhanced transcription of Mbnl1 mRNA. Second, PBZ attenuated binding of MBNL1 to abnormally expanded CUG repeats in cellulo and in vitro. Our studies suggest that PBZ is a potent therapeutic agent for DM1 that upregulates availability of MBNL1.
  • Hiroki Imada, Takashi Sakatani, Mikio Sawada, Tohru Matsuura, Noriyoshi Fukushima, Imaharu Nakano
    PATHOLOGY INTERNATIONAL 65 10 549 - 553 2015年10月 [査読有り][通常論文]
     
    Rosai-Dorfman disease (RDD) is a benign histiocytic proliferative disorder characterized by the accumulation of histiocytes in lymph nodes and various other organs. RDD seldom involves the central nervous system, and cases of purely intracranial RDD are particularly rare. We report a case of purely intracranial RDD involving the brainstem that was diagnosed at autopsy. A 68-year-old woman visited our hospital because of visual disturbances and loss of energy. Magnetic resonance imaging revealed an obscure mass in the brainstem. Despite exhaustive work-ups, the etiology of the intracranial mass remained unclear. The patient died of respiratory depression, and an autopsy was performed for pathological investigation. Macroscopically, a pink pale mass 2.5cm in diameter was found in the brainstem, with no attachment to the dura. Histologically, it was composed of histiocytic cells with incorporation of small lymphocytes (emperipolesis). Immunohistochemical staining revealed that the cells were positive for CD68 and S100 and negative for CD1a, consistent with a diagnosis of RDD. Purely intracranial RDD is extremely rare and considered benign. To date, nine cases (including ours) have been reported. To our knowledge, this is the first case of intracranial RDD with autopsy. Although generally considered benign, RDD involving the brainstem might be lethal.
  • Rui Gao, Yongping Liu, Anabela Silva-Fernandes, Xiang Fang, Adriana Paulucci-Holthauzen, Arpita Chatterjee, Hang L. Zhang, Tohru Matsuura, Sanjeev Choudhary, Tetsuo Ashizawa, Arnulf H. Koeppen, Patricia Maciel, Tapas K. Hazra, Partha S. Sarkar
    PLOS GENETICS 11 1 e1004834  2015年01月 [査読有り][通常論文]
     
    Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-delta pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.
  • Tomoaki Kameda, Michito Namekawa, Haruo Shimazaki, Daisuke Minakata, Tohru Matsuura, Imaharu Nakano
    CEPHALALGIA 34 13 1093 - 1096 2014年11月 [査読有り][通常論文]
     
    Background Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and reversible cerebral vasoconstriction on angiographic findings. It can be difficult to diagnose when initial angiography is normal. Case results A 30-year-old woman was admitted because of sudden-onset thunderclap headache and seizure on postpartum day 7. Brain MRI on fluid-attenuated inversion recovery (FLAIR) showed hyperintense vessel sign (HVS), which usually means slow flow due to severe proximal arterial stenosis. However, magnetic resonance angiography (MRA) indicated that proximal arteries was normal. After nicardipine treatment, her symptoms improved dramatically. Follow-up FLAIR on day 7 showed complete resolution of HVS, while a series of MRAs revealed reversible multifocal segmental vasoconstriction. Conclusions HVS on initial FLAIR is useful for an early diagnosis of reversible cerebral vasoconstriction syndrome. As the delayed vasoconstriction on MRA can be observed, reversible cerebral vasoconstriction syndrome may progress from distal small to proximal larger arteries.
  • Yoshihiro Yamashita, Tohru Matsuura, Tatsuaki Kurosaki, Yoshinobu Amakusa, Masanobu Kinoshita, Tohru Ibi, Ko Sahashi, Kinji Ohno
    NEUROBIOLOGY OF DISEASE 69 200 - 205 2014年09月 [査読有り][通常論文]
     
    Myotonic dystrophy type 1 (DM1) is caused by transcription of CUG repeat RNA, which causes sequestration of muscleblind-like 1 (MBNL1) and upregulation of CUG triplet repeat RNA-binding protein (CUG-BP1). In DM1, dysregulation of these proteins contributes to many aberrant splicing events, causing various symptoms of the disorder. Here, we demonstrate the occurrence of aberrant splicing of LIM domain binding 3 (LDB3) exon 11 in DM1 skeletal muscle. Exon array surveys, RT-PCR, and western blotting studies demonstrated that exon 11 inclusion was DM1 specific and could be reproduced by transfection of a minigene containing the CTG repeat expansion. Moreover, we found that the LDB3 exon 11-positive isoform had reduced affinity for PKC compared to the exon 11-negative isoform. Since PKC exhibits hyperactivation in DM1 and stabilizes CUG-BP1 by phosphorylation, aberrant splicing of LDB3 may contribute to CUG-BP1 upregulation through changes in its affinity for PKC. (C) 2014 Elsevier Inc All rights reserved.
  • Kota Sato, Nobutoshi Morimoto, Kentaro Deguchi, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF CLINICAL NEUROSCIENCE 21 8 1341 - 1343 2014年08月 [査読有り][通常論文]
     
    Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder that causes muscle weakness, disability, respiratory failure, and eventually death. However, some ALS patients are diagnosed only after development of respiratory failure. To study the reason for delayed diagnosis of ALS, we reviewed cases of ALS patients with respiratory failure. We retrospectively reviewed all 200 patients diagnosed with sporadic ALS in our hospital from January 2001 to April 2011. Among them, we focused on seven patients who were diagnosed only after developing respiratory failure. We reviewed their clinical characteristics and demographics. The mean time from onset to a correct diagnosis was 15.6 +/- standard deviation of 8.0 months. Two patients had already been intubated at a previous hospital because they presented with severe respiratory failure and required emergency intubation. One patient was intubated upon arrival to our hospital. We identified three reasons for the delay in diagnosis: delayed referral to a neurologist (four patients); a shortage of neurologists in rural areas (three patients); and an atypical clinical course with respiratory failure as the initial symptom (two patients). Three patients had undergone emergency intubation without giving informed consent. To provide an informed choice and to avoid unwanted intubation for ALS patients, we suggest extending neurological knowledge of ALS to general practitioners. (C) 2014 Elsevier Ltd. All rights reserved.
  • Takahiro Nakayama, Harumasa Nakamura, Yasushi Oya, Takashi Kimura, Ichiro Imahuku, Kinji Ohno, Ichizo Nishino, Koji Abe, Tohru Matsuura
    JOURNAL OF HUMAN GENETICS 59 3 129 - 133 2014年03月 [査読有り][通常論文]
     
    Myotonic dystrophy type 2 (DM2) is more common than DM1 in Europe and is considered a rare cause of myotonic dystrophies in Asia. Its clinical course is also milder with more phenotypic variability than DM1. We herein describe the first known Asian family (three affected siblings) with DM2 based on clinical and genetic analyses. Notably, two of the affected siblings were previously diagnosed with limb-girdle muscular dystrophy. Myotonia (the inability of the muscle to relax) was absent or only faintly present in these individuals. The third sibling had grip myotonia and is the first known Asian DM2 patient. The three DM2 siblings share several systemic characteristics, including late-onset, proximal-dominant muscle weakness, diabetes, cataracts and asthma. Repeat-primed PCR across the DM2 repeat revealed a characteristic ladder pattern of a CCTG expansion in all siblings. Southern blotting analysis identified the presence of 3400 repeats. Further DM2 studies in Asian populations are needed to define the clinical presentation of Asian DM2 and as yet unidentified phenotypic differences from Caucasian patients.
  • NVU保護作用を介したスタチンのアルツハイマー病に対する予防効果
    倉田 智子, 宮崎 一徳, 森本 展年, 太田 康之, 表 芳夫, 池田 佳生, 松浦 徹, 阿部 康二
    臨床神経学 53 12 1483 - 1483 (一社)日本神経学会 2013年12月
  • アルツハイマー病に対するスタチンのNVUへの保護効果の検討
    倉田 智子, 宮崎 一徳, 森本 展年, 太田 康之, 出口 健太郎, 池田 佳生, 松浦 徹, 阿部 康二
    Dementia Japan 27 4 512 - 512 (一社)日本認知症学会 2013年10月
  • 岡山大学神経内科でのDonepezilとGalantamineの比較検討
    倉田 智子, 佐藤 恒太, 表 芳夫, 太田 康之, 池田 雅美, 出口 健太郎, 出口 章子, 池田 佳生, 松浦 徹, 阿部 康二
    日本老年医学会雑誌 50 5 691 - 691 (一社)日本老年医学会 2013年09月
  • Tohru Matsuura, Tatsuaki Kurosaki, Yoshio Omote, Narihiro Minami, Yukiko K Hayashi, Ichizo Nishino, Koji Abe
    Journal of human genetics 58 8 564 - 5 2013年08月 [査読有り][通常論文]
  • Syoichiro Kono, Kentaro Deguchi, Nobutoshi Morimoto, Tomoko Kurata, Shoko Deguchi, Tohru Yamashita, Yoshio Ikeda, Tohru Matsuura, Hisashi Narai, Nobuhiko Omori, Yasuhiro Manabe, Taijyun Yunoki, Yoshiki Takao, Sanami Kawata, Kenichi Kashihara, Koji Abe
    Journal of Stroke and Cerebrovascular Diseases 22 3 190 - 196 2013年04月 [査読有り][通常論文]
     
    In October 2005 in Japan, the recombinant tissue plasminogen activator (tPA) alteplase was approved for patients with acute ischemic stroke within 3 hours of onset at a dose of 0.6 mg/kg. The present study was undertaken to assess the safety and efficacy of alteplase in Japan. Between October 2005 and December 2009, a total of 114 consecutive patients admitted to 4 hospitals received intravenous tPA within 3 hours of stroke onset. Clinical backgrounds and outcomes were investigated. The patients were divided into 2 chronological groups: an early group, comprising 45 patients treated between October 2005 and December 2007, and a later group, comprising 69 patients treated between January 2008 and December 2009. The mean time from arrival at the hospital to the initiation of treatment was significantly reduced in the later group, from 82.6 minutes to 70.9 minutes. Intracerebral hemorrhage (ICH) occurred in 26 patients (22.8%) compared with patients without ICH, these patients had a significantly higher prevalence of cardiogenic embolism (88.5% vs 58.0%) greater warfarin use (26.8% vs 6.8%) higher mean National Institutes of Health Stroke Scale (NIHSS) scores on admission (16 vs 10), at 3 days after admission (14 vs 5), and at 7 days after admission (13.5 vs 3) and a lower Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (7.8 vs 9.1). Patients who received edaravone had a higher prevalence of cardiogenic embolism (70.9% vs 36.4%), a higher recanalization rate (77.7% vs 36.4%), and lower NIHSS scores on admission and at 3 and 7 days after admission compared with those who did not receive edaravone. Our data suggest that administration of intravenous alteplase 0.6 mg/kg within 3 hours of stroke onset is safe and effective, that the NIHSS and Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score are useful predictors of ICH after tPA administration, and that warfarin-treated patients are more likely to develop symptomatic ICH despite an International Normalized Ratio < 1.7. © 2013 by National Stroke Association.
  • Oscar Hernandez-Hernandez, Celine Guiraud-Dogan, Geraldine Sicot, Aline Huguet, Sabrina Luilier, Esther Steidl, Stefanie Saenger, Elodie Marciniak, Helene Obriot, Caroline Chevarin, Annie Nicole, Lucile Revillod, Konstantinos Charizanis, Kuang-Yung Lee, Yasuhiro Suzuki, Takashi Kimura, Tohru Matsuura, Bulmaro Cisneros, Maurice S. Swanson, Fabrice Trovero, Bruno Buisson, Jean-Charles Bizot, Michel Hamon, Sandrine Humez, Guillaume Bassez, Friedrich Metzger, Luc Buee, Arnold Munnich, Nicolas Sergeant, Genevieve Gourdon, Mario Gomes-Pereira
    BRAIN 136 957 - 970 2013年03月 [査読有り][通常論文]
     
    Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology.
  • アルツハイマー病モデルマウスを用いたスタチンによる抗炎症効果の検討
    倉田 智子, 宮崎 一徳, 森本 展年, 太田 康之, 池田 佳生, 松浦 徹, 阿部 康二
    臨床神経学 52 12 1557 - 1557 (一社)日本神経学会 2012年12月
  • Xuemei Zhang, Fengfeng Tian, Hiromi Kawai, Tomoko Kurata, Shoko Deguchi, Kentaro Deguchi, Jingwei Shang, Ning Liu, Wentao Liu, Yoshio Ikeda, Tohru Matsuura, Tatsushi Kamiya, Koji Abe
    Translational Stroke Research 3 4 435 - 441 2012年12月 [査読有り][通常論文]
     
    To investigate the effects of amlodipine in combination with atorvastatin on carotid atherosclerotic changes in metabolic syndrome, 8-week-old Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or amlodipine in combination with atorvastatin for 28 days. Histological studies of common carotid arteries showed that lipid deposition determined by Sudan III staining was significantly reduced in rats treated with amlodipine or atorvastatin alone and was further reduced by amlodipine in combination with atorvastatin. Immunohistochemical studies of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, the arterial calcification initiator bone morphogenetic protein (BMP) 2, the angiogenic factor Notch1, and the smooth muscle cell marker α-smooth muscle actin (SMA) showed that the high expression of all four protein in vehicle-treated rats was greatly decreased by amlodipine, atorvastatin, or amlodipine in combination with atorvastatin, in ascending order. Double immunostaining showed marked colocalization of TNF-α with bone morphogenetic protein 2 and Notch1 with α-SMA in the vehicle group, which was greatly reduced by amlodipine plus atorvastatin. These data suggest that combination therapy may be more effective in preventing atherosclerotic processes and subsequent carotid vascular events than administrating amlodipine or atorvastatin alone in metabolic syndrome. © 2012 Springer Science+Business Media, LLC.
  • 岡山大学病院神経内科における認知症診療
    倉田 智子, 表 芳夫, 太田 康之, 池田 雅美, 森本 展年, 池田 佳生, 松浦 徹, 阿部 康二
    日本老年医学会雑誌 49 6 824 - 825 (一社)日本老年医学会 2012年11月
  • 地域住民の一般健診受診者におけるタッチパネル式簡易認知症スクリーニング検査の有用性
    表 芳夫, 倉田 智子, 太田 康之, 池田 雅美, 森本 展年, 池田 佳生, 松浦 徹, 阿部 康二
    日本老年医学会雑誌 49 6 825 - 825 (一社)日本老年医学会 2012年11月
  • 佐藤 恒太, 森本 展年, 倉田 智子, 太田 康之, 出口 健太郎, 池田 佳生, 松浦 徹, 阿部 康二
    神経治療学 29 5 645 - 645 (一社)日本神経治療学会 2012年09月
  • 佐藤 恒太, 倉田 智子, 太田 康之, 池田 雅美, 河野 祥一郎, 出口 健太郎, 出口 章子, 池田 佳生, 亀高 さつき, 村岡 万梨絵, 薮中 裕子, 松浦 徹, 阿部 康二
    神経治療学 29 5 668 - 668 (一社)日本神経治療学会 2012年09月
  • Tatsuaki Kurosaki, Shintaroh Ueda, Takafumi Ishida, Koji Abe, Kinji Ohno, Tohru Matsuura
    PLoS ONE 7 6 e38379 - - 2012年06月 [査読有り][通常論文]
     
    Myotonic dystrophy type 2 (DM2) is a subtype of the myotonic dystrophies, caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the zinc finger protein 9 (ZNF9) gene. The expansions are extremely unstable and variable, ranging from 75-11,000 CCTG repeats. This unprecedented repeat size and somatic heterogeneity make molecular diagnosis of DM2 difficult, and yield variable clinical phenotypes. To better understand the mutational origin and instability of the ZNF9 CCTG repeat, we analyzed the repeat configuration and flanking regions in 26 primate species. The 3′-end of an AluSx element, flanked by target site duplications (5′-ACTRCCAR-3′or 5′-ACTRCCARTTA-3′), followed the CCTG repeat, suggesting that the repeat was originally derived from the Alu element insertion. In addition, our results revealed lineage-specific repetitive motifs: pyrimidine (CT)-rich repeat motifs in New World monkeys, dinucleotide (TG) repeat motifs in Old World monkeys and gibbons, and dinucleotide (TG) and tetranucleotide (TCTG and/or CCTG) repeat motifs in great apes and humans. Moreover, these di- and tetra-nucleotide repeat motifs arose from the poly (A) tail of the AluSx element, and evolved into unstable CCTG repeats during primate evolution. Alu elements are known to be the source of microsatellite repeats responsible for two other repeat expansion disorders: Friedreich ataxia and spinocerebellar ataxia type 10. Taken together, these findings raise questions as to the mechanism(s) by which Alu-mediated repeats developed into the large, extremely unstable expansions common to these three disorders. © 2012 Kurosaki et al.
  • 脳卒中易発症高血圧ラット(SHR-SP)におけるシロスタゾールの多面的効果の検討
    表 芳夫, 出口 健太郎, 田 豊豊, 河相 裕美, 劉 文涛, 劉 檸, 倉田 智子, 山下 徹, 太田 康之, 池田 佳生, 松浦 徹, 阿部 康二
    日本抗加齢医学会総会プログラム・抄録集 12回 185 - 185 (一社)日本抗加齢医学会 2012年06月
  • Yoshihiro Yamashita, Tohru Matsuura, Jun Shinmi, Yoshinobu Amakusa, Akio Masuda, Mikako Ito, Masanobu Kinoshita, Hirokazu Furuya, Koji Abe, Tohru Ibi, Koo Sahashi, Kinji Ohno
    Journal of Human Genetics 57 6 368 - 374 2012年06月 [査読有り][通常論文]
     
    Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles. We analyzed 72 exons by RT-PCR and found that 27 were aberrantly spliced, whereas 45 were not. Among these, 25 were novel and especially splicing aberrations of LDB3 exon 4 and TTN exon 45 were unique to DM1. Retrospective analysis revealed that four parameters efficiently detect aberrantly spliced exons: (i) the signal intensity is high (ii) the ratio of probe sets with reliable signal intensities (that is, detection above background P-value0.000) is high within a gene (iii) the splice index (SI) is high and (iv) SI is deviated from SIs of the other exons that can be estimated by calculating the deviation value (DV). Application of the four parameters gave rise to a sensitivity of 77.8% and a specificity of 95.6% in our data set. We propose that calculation of DV, which is unique to our analysis, is of particular importance in analyzing the exon array data. © 2012 The Japan Society of Human Genetics All rights reserved.
  • Nobutoshi Morimoto, Kazunori Miyazaki, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, Dongchon Kang, Tomomi Ide, Koji Abe
    Journal of Neuroscience Research 90 6 1200 - 1208 2012年06月 [査読有り][通常論文]
     
    Increasing evidence indicates that oxidative stress is an important mechanism underlying motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). Mitochondrial DNA (mtDNA) is highly susceptible to oxidative damage and has little potential for repair, although mitochondrial transcription factor A (TFAM) plays essential roles in maintaining mitochondrial DNA by reducing oxidative stress, promoting mtDNA transcription, and regulating mtDNA copy number. To analyze a possible therapeutic effect of TFAM on ALS pathology, double transgenic mice overexpressing G93A mutant SOD1 (G93ASOD1) and human TFAM (hTFAM) were newly generated in the present study. Rotarod scores were better in G93ASOD1/hTFAM double-Tg mice than G93ASOD1 single-Tg mice at an early symptomatic stage, 15 and 16 weeks of age, with a 10% extension of the onset age in double-Tg mice. The number of surviving MNs was 30% greater in double-Tg mice with end-stage disease, at 19 weeks, with remarkable reductions in the amount of the oxidative stress marker 8-OHdG and the apoptotic marker cleaved caspase 3 and with preserved COX1 expression. Double-immunofluorescence study showed that hTFAM was expressed specifically in MNs and microglia in the spinal cords of double-Tg mice. The present study suggests that overexpression of TFAM has a potential to reduce oxidative stress in MN and delay onset of the disease in ALS model mice. © 2012 Wiley Periodicals, Inc.
  • Kota Sato, Nobutoshi Morimoto, Tohru Matsuura, Yasuyuki Ohta, Masatoshi Tsunoda, Yoshio Ikeda, Koji Abe
    Neurological Research 34 5 512 - 517 2012年06月 [査読有り][通常論文]
     
    Objective: To assess cerebrospinal fluid (CSF) flow dynamics involvement in the pathogenesis of amyotrophic lateral sclerosis (ALS), we conducted CSF flow studies on 40 individuals with motor neuron diseases (MNDs) including ALS, and 28 age-matched normal and disease [cervical spondylosis (CS)] controls. Methods: The CSF pulsatile velocity anterior to the cervical cord at level C5 during one heart beat was determined non-invasively by phase-contrast electrocardiography-triggered magnetic resonance imaging. Results: In MND, caudal CSF velocity peaked at 25% of the cardiac cycle after the R wave (UTc/RR), showing an increased delay in comparison to normal controls, while amplitude Hc was significantly larger than that in CS. Discussion: We conclude that CSF flow dynamics of MND differ from those of controls and may thus facilitate differentiation of MND from CS. © W. S. Maney & Son Ltd 2012.
  • 岡山大学病院神経内科における認知症診療
    倉田 智子, 尾関 太一, 太田 康之, 池田 雅美, 森本 展年, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    臨床神経学 52 5 388 - 388 (一社)日本神経学会 2012年05月
  • Tohru Matsuura, Narihiro Minami, Hajime Arahata, Kinji Ohno, Koji Abe, Yukiko K Hayashi, Ichizo Nishino
    Journal of human genetics 57 3 219 - 20 2012年03月 [査読有り][通常論文]
  • Tomoko Kurata, Yoshio Omote, Masami Ikeda, Nobutoshi Morimoto, Satsuki Kametaka, Marie Muraoka, Yuko Yabunaka, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    2012 ICME International Conference on Complex Medical Engineering, CME 2012 Proceedings 215 - 217 2012年 [査読有り][通常論文]
     
    The needs and importance of the simple screening examination for dementia have risen recently. In the present study, we corrected the patients of Alzheimer's disease, and performed the standard examination for dementia and a simple computerized touch panel-type screening test for the early diagnosis of dementia (touch panel-type screening test), and compared the scores. There is a good correlation MMSE score and a simple computerized touch panel-type screening test by single regression analysis. And so, a simple computerized touch panel-type screening test is very useful for assessment of dementia. © 2012 IEEE.
  • Kentaro Deguchi, Syoichiro Kono, Shoko Deguchi, Nobutoshi Morimoto, Masami Ikeda, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, Takashi Kanbayashi, Toshiyuki Takahashi, Koji Abe
    JOURNAL OF THE NEUROLOGICAL SCIENCES 312 1-2 18 - 20 2012年01月 [査読有り][通常論文]
     
    Here we report a case with positive serum anti-aquaporin 4 (AQP4) antibody who presented with hypersomnolence, symmetrical hypothalamic lesions and a reduced CSF orexin (hypocretin) level without optic nerve and spinal cord lesions on MRI. All of the symptoms, MRI finding and CSF orexin level improved simultaneously after steroid therapy. AQP4 is a member of the AQP superfamily which is strongly expressed in the hypothalamus where orexin (hypocretin)-containing neurons are primarily concentrated. Although there have been only a few reports similar to our case, the present case suggests a close relationship between the positive serum anti-AQP4 antibody and symmetrical hypothalamic lesions with hypersomnolence and without optic /spinal lesion, which is improved by steroid treatment. 2011 Elsevier B.V. All rights reserved.
  • アルツハイマー型認知症患者におけるタッチパネル式簡易認知症スクリーニング検査の有用性
    倉田 智子, 表 芳夫, 太田 康之, 池田 雅美, 森本 展年, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    神経心理学 27 4 347 - 347 日本神経心理学会 2011年12月
  • 岡山大学病院神経内科における認知症診療
    倉田 智子, 太田 康之, 池田 雅美, 森本 展年, 尾関 太一, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    神経心理学 27 4 348 - 348 日本神経心理学会 2011年12月
  • SCA31および他の小脳失調症における聴覚障害の検討
    池田 佳生, 倉田 智子, 山下 徹, 太田 康之, 出口 章子, 出口 健太郎, 武久 康, 城 洋志彦, 松浦 徹, 阿部 康二
    臨床神経学 51 12 1358 - 1358 (一社)日本神経学会 2011年12月
  • ALSモデルマウス脊髄血管におけるneurovascular unitの異常
    河野 祥一郎, 宮崎 一徳, 太田 康之, 森本 展年, 倉田 智子, 池田 佳生, 松浦 徹, 阿部 康二
    臨床神経学 51 12 1361 - 1361 (一社)日本神経学会 2011年12月
  • 筋強直性ジストロフィー2型(DM2)患者の筋CT所見
    中山 貴博, 今福 一郎, 中村 治雅, 大矢 寧, 西野 一三, 松浦 徹, 阿部 康二
    臨床神経学 51 12 1383 - 1383 (一社)日本神経学会 2011年12月 [査読有り][通常論文]
  • AmlodipineとAtorvastatin併用によるZuckerラット脳梗塞モデルにおける神経保護効果
    河相 裕美, 出口 健太郎, 出口 章子, 山下 徹, 太田 康之, 表 芳夫, 倉田 智子, 池田 佳生, 松浦 徹, 阿部 康二
    脳循環代謝 23 1 132 - 132 (一社)日本脳循環代謝学会 2011年11月
  • 当院における特発性低髄液圧症候群4例の検討
    出口 健太郎, 松薗 構佑, 香西 由子, 河野 祥一郎, 出口 章子, 森本 展年, 倉田 智子, 池田 佳生, 松浦 徹, 阿部 康二
    日本頭痛学会誌 38 2 256 - 256 (一社)日本頭痛学会 2011年11月 [査読有り][通常論文]
  • Hiroshi Kaneko, Hiroshi Kitoh, Tohru Matsuura, Akio Masuda, Mikako Ito, Monica Mottes, Frank Rauch, Naoki Ishiguro, Kinji Ohno
    HUMAN GENETICS 130 5 671 - 683 2011年11月 [査読有り][通常論文]
     
    Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2. We identified a dominant missense mutation, c.3235G > A in COL1A1 exon 45 predicting p.G1079S, in a Japanese family with mild OI. As mutations in exon 45 exhibit mild to lethal phenotypes, we tested if disruption of an exonic splicing cis-element determines the clinical phenotype, but detected no such mutations. In the Japanese family, juvenile-onset hyperuricemia cosegregated with OI, but not in the previously reported Italian and Canadian families with c.3235G > A. After confirming lack of a founder haplotype in three families, we analyzed PRPSAP1 and PRPSAP2 as candidate genes for hyperuricemia on chr 17 where COL1A1 is located, but found no mutation. We next resequenced the whole exomes of two siblings in the Japanese family and identified variable numbers of previously reported hyperuricemia-associated SNPs in ABCG2 and SLC22A12. The same SNPs, however, were also detected in normouricemic individuals in three families. We then identified two missense SNVs in ZPBP2 and GPATCH8 on chromosome 17 that cosegregated with hyperuricemia in the Japanese family. ZPBP2 p.T69I was at the non-conserved region and was predicted to be benign by in silico analysis, whereas GPATCH8 p.A979P was at a highly conserved region and was predicted to be deleterious, which made p.A979P a conceivable candidate for juvenile-onset hyperuricemia. GPATCH8 is only 5.8 Mbp distant from COL1A1 and encodes a protein harboring an RNA-processing domain and a zinc finger domain, but the molecular functions have not been elucidated to date.
  • Nobuhito Tanaka, Yoshio Ikeda, Yasuyuki Ohta, Kentaro Deguchi, Fengfeng Tian, Jingwei Shang, Tohru Matsuura, Koji Abe
    Brain Research 1370 246 - 253 2011年10月 [査読有り][通常論文]
     
    Reactive oxygen species and their detrimental effects on the brain after transient ischemia have been implicated in the pathogenesis of the ischemic injury. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system is currently recognized as the major cellular defense mechanism under oxidative stress, but the involvement of the Keap1-Nrf2 system in the ischemic brain injuries has not been fully investigated to date. In the present study, we investigated temporal changes of Keap1, Nrf2, and their downstream antioxidative proteins in post-ischemic mice brains with respect to spacial differences between the peri-infarct regions and the regions destined to infarct. In the peri-infarct regions, a steady level of Keap1 showed a decremental expression started at 2 h of reperfusion after 60 min of transient middle cerebral artery occlusion (tMCAO). In contrast, Nrf2 began to show a significant increase at 2 h with a peak at 8 h of reperfusion after tMCAO. Both Keap1 and Nrf2 are mainly expressed in neuronal cells but not in glial cells. In the same peri-infarct region, downstream antioxidative proteins such as thioredoxin, glutathione, and heme oxygenase-1 showed significant increases at later time-points of 24-72 h of reperfusion after tMCAO. In the regions destined to infarct, a similar trend of expression changes to those in the peri-infarct regions was observed in Keap1, Nrf2, and 3 downstream antioxidative proteins with much less reactions. The changes found in this study suggest that the induced antioxidative stress proteins after cerebral ischemia may play an important endogenous neuroprotective response under oxidative stress after ischemic stroke. © 2010 Elsevier B.V.
  • タッチパネル式簡易認知症スクリーニング検査のアルツハイマー型認知症患者における有用性
    倉田 智子, 表 芳夫, 太田 康之, 池田 雅美, 森本 展年, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    Dementia Japan 25 3 319 - 319 (一社)日本認知症学会 2011年10月
  • 地域住民の一般健診受診者におけるタッチパネル式簡易認知症スクリーニング検査の有用性
    表 芳夫, 倉田 智子, 太田 康之, 池田 雅美, 森本 展年, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    Dementia Japan 25 3 388 - 388 (一社)日本認知症学会 2011年10月
  • アルツハイマー病モデルマウスを用いたスタチンの認知機能への効果の検討
    倉田 智子, 宮崎 一徳, 森本 展年, 太田 康之, 池田 佳生, 松浦 徹, 阿部 康二
    Dementia Japan 25 3 420 - 420 (一社)日本認知症学会 2011年10月
  • 家系内に他の発症者を認めないM232R変異陽性家族性プリオン病の1例
    松薗 構佑, 池田 佳生, 香西 由子, 出口 章子, 倉田 智子, 森本 展年, 出口 健太郎, 松浦 徹, 阿部 康二
    NEUROINFECTION 16 2 190 - 190 日本神経感染症学会 2011年10月 [査読有り][通常論文]
  • アルツハイマー型認知症患者におけるタッチパネル式簡易認知症スクリーニング検査の有用性
    倉田 智子, 表 芳夫, 太田 康之, 池田 雅美, 森本 展年, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    日本神経心理学会総会プログラム・予稿集 35回 127 - 127 日本神経心理学会 2011年08月
  • 岡山大学病院神経内科における認知症診療
    倉田 智子, 太田 康之, 池田 雅美, 森本 展年, 尾関 太一, 亀高 さつき, 村岡 万梨絵, 藪中 裕子, 池田 佳生, 松浦 徹, 阿部 康二
    日本神経心理学会総会プログラム・予稿集 35回 127 - 127 日本神経心理学会 2011年08月
  • Xuemei Zhang, Shoko Deguchi, Kentaro Deguchi, Yasuyuki Ohta, Toru Yamashita, Jingwei Shang, Fengfeng Tian, Ning Liu, Wentao Liu, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF NEUROSCIENCE RESEARCH 89 8 1228 - 1234 2011年08月 [査読有り][通常論文]
     
    We examined the neuroprotective effects amlodipine and/or atorvastatin in metabolic syndrome (MetS) Zucker fatty rats against transient (90 min) middle cerebral artery occlusion (MCAO). The rats were pretreated with vehicle, amlodipine, atorvastatin, or amlodipine plus atorvastatin for 28 days, and 24 hr after transient MCAO the infarct size was assessed via hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and microtubule-associated protein 1 light chain 3 (LC3) expression were examined by immunohistochemistry to evaluate apoptosis and autophagy, respectively. Compared with the vehicle group, rats treated with amlodipine or atorvastatin alone showed a significant decrease in infarct volume (P < 0.01), which was further decreased in the amlodipine plus atorvastatin group (P < 0.001). Compared with the vehicle group, the numbers of TUNEL- and LC3-positive cells were markedly reduced by amlodipine or atorvastatin alone (P < 0.01) and further decreased by amlodipine plus atorvastatin (P < 0.001). The number of apoptotic TUNEL/autophagic LC3 double-positive cells was also significantly decreased with amlodipine or atorvastatin alone compared with vehicle (P < 0.01) and was further decreased by amlodipine plus atorvastatin (P < 0.001). These data suggest additive neuroprotective effects of combination amlodipine and atorvastatin treatment after acute ischemic stroke in MetS model Zucker rats. These effects are mediated, at least in part, via antiapoptotic and antiautophagic mechanisms. Further studies are now needed to expand these preliminary results to understand fully the mechanisms involved in the protective effects of amlodipine and atorvastatin against ischemic stroke. (C) 2011 Wiley-Liss, Inc.
  • Nobutoshi Morimoto, Kentaro Deguchi, Kota Sato, Taijun Yunoki, Shoko Deguchi, Yasuyuki Ohta, Tomoko Kurata, Yoshiki Takao, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF THE NEUROLOGICAL SCIENCES 307 1-2 74 - 78 2011年08月 [査読有り][通常論文]
     
    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease, which is characterized by progressive degeneration of spinal and bulbar innervating motor neurons. However, the underlying mechanisms of motor neuron death remain poorly understood. Several candidate disease biomarkers have been detected in cerebrospinal fluid of ALS patients. The present study analyzed various cerebral spinal fluid gas parameters in ALS patients and compared these values to controls, as well as patients with cervical spondylosis, Parkinson syndrome, and spinocerebellar degeneration. Cerebral spinal fluid pH positively correlated with the ALS functional rating scale in total and limb-type ALS patients. In addition, cerebral spinal fluid pH positively correlated with shorter disease duration (less than 22 weeks). These results suggested that cerebral spinal fluid pH provides a biomarker for ALS and could reflect mechanisms of disease progression in ALS patients. (C) 2011 Elsevier B.V. All rights reserved.
  • Motonori Takamiya, Yusei Miyamoto, Toru Yamashita, Kentaro Deguchi, Yasuyuki Ohta, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF NEUROSCIENCE RESEARCH 89 7 1125 - 1133 2011年07月 [査読有り][通常論文]
     
    Ischemic stroke is a major, urgent neurologic disorder in which reactive oxygen species (ROS) are deeply involved in the detrimental effects. Platinum nanoparticle (nPt) species are a novel and strong scavenger of such ROS, so we examined the clinical and neuroprotective effects of nPts in mouse ischemic brain. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. Upon reperfusion, nPt or vehicle was administered intravenously. At 48 hr after the tMCAO, motor function, infarct volume, immunohistochemistry of neurovascular components (endothelial NAGO, tight junctional occludin, and basal laminal collagen IV), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 hr after tMCAO was determined with oxidized hydroethidine. Compared with vehicle, treatment with nPts significantly improved the motor function and greatly reduced the infarct volume, especially in the cerebral cortex. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin but a great decrease of collagen IV and a remarkable increase of MMP-9. Treatment with nPts greatly reduced this decrease of collagen IV and activation of MMP-9 and, with large reductions of MMP-9 activation on zymography and superoxide production. The present study demonstrates that treatment with nPts ameliorates the neurological scores with a large reduction in infarct size as well as the preservation of outer components of the neurovascular unit (collagen IV) and inactivation of MMP-9. A strong reduction of superoxide anion production by nPts could account for such remarkable neurobehavioral and neuroprotective effects on ischemic stroke. (C) 2011 Wiley-Liss, Inc.
  • Hatasu Kobayashi, Koji Abe, Tohru Matsuura, Yoshio Ikeda, Toshiaki Hitomi, Yuji Akechi, Toshiyuki Habu, Wanyang Liu, Hiroko Okuda, Akio Koizumi
    AMERICAN JOURNAL OF HUMAN GENETICS 89 1 121 - 130 2011年07月 [査読有り][通常論文]
     
    Autosomal-dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. In this study, we performed genetic analysis of a unique form of SCA (SCA36) that is accompanied by motor neuron involvement. Genome-wide linkage analysis and subsequent fine mapping for three unrelated Japanese families in a cohort of SCA cases, in whom molecular diagnosis had never been performed, mapped the disease locus to the region of a 1.8 Mb stretch (LOD score of 4.60) on 20p13 (D20S906-D20S193) harboring 37 genes with definitive open reading frames. We sequenced 33 of these and observed a large expansion of an intronic GGCCTG hexanucleotide repeat in NOP56 and an unregistered missense variant (Phe265Leu) in C20orf194, but we found no mutations in PDYN and TGM6. The expansion showed complete segregation with the SCA phenotype in family studies, whereas Phe265Leu in C20orf194 did not. Screening of the expansions in the SCA cohort cases revealed four additional occurrences, but none were revealed in the cohort of 27 Alzheimer disease cases, 154 amyotrophic lateral sclerosis cases, or 300 controls. In total, nine unrelated cases were found in 251 cohort SCA patients (3.6%). A founder haplotype was confirmed in these cases. RNA foci formation was detected in lymphoblastoid cells from affected subjects by fluorescence in situ hybridization. Double staining and gel-shift assay showed that (GGCCUG)n binds the RNA-binding protein SRSF2 but that (CUG)(6) does not. In addition, transcription of MIR1292, a neighboring miRNA, was significantly decreased in lymphoblastoid cells of SCA patients. Our finding suggests that SCA36 is caused by hexanucleotide repeat expansions through RNA gain of function.
  • ALSモデルマウス脊髄微小血管のIn vivoイメージング
    宮崎 一徳, 正本 和人, 森本 展年, 太田 康之, 倉田 智子, 池田 佳生, 松浦 徹, 小畠 隆行, 菅野 巌, 阿部 康二
    JSMI Report 4 2 178 - 178 日本分子イメージング学会 2011年05月
  • Kazunori Miyazaki, Yasuyuki Ohta, Makiko Nagai, Nobutoshi Morimoto, Tomoko Kurata, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF NEUROSCIENCE RESEARCH 89 5 718 - 728 2011年05月 [査読有り][通常論文]
     
    Recent reports suggest that functional or structural defect of vascular components are implicated in amyotrophic lateral sclerosis (ALS) pathology. In the present study, we examined a possible change of the neurovascular unit consisting of endothelium (PCAM-1), tight junction (occludin), and basement membrane (collagen IV) in relation to a possible activation of MMP-9 in ALS patients and ALS model mice. We found that the damage in the neurovascular unit was more prominent in the outer side and preferentially in the anterior horn of ALS model mice. This damage occurred prior to motor neuron degeneration and was accompanied by MMP-9 up-regulation. We also found the dissociation between the PCAM-1-positive endothelium and GFAP-positive astrocyte foot processes in both humans and the animal model of ALS. The present results indicate that perivascular damage precedes the sequential changes of the disease, which are held in common between humans and the animal model of ALS, suggesting that the neurovascular unit is a potential target for therapeutic intervention in ALS. (C) 2011 Wiley-Liss, Inc.
  • Yoshio Ikeda, Makiko Nagai, Tomoko Kurata, Toru Yamashita, Yasuyuki Ohta, Shoko Nagotani, Kentaro Deguchi, Yasushi Takehisa, Yoshihiko Shiro, Tohru Matsuura, Koji Abe
    NEUROLOGICAL RESEARCH 33 4 427 - 432 2011年05月 [査読有り][通常論文]
     
    Objective: To investigate whether acoustic impairment can be one of the characteristic extracerebellar symptoms in sporadic and hereditary ataxias including spinocerebellar ataxia type 31 (SCA31). Methods: We investigated genotypes of dominant ataxia families, and determined a frequency of each form in our cohort of 154 families. Acoustic function in the groups of various forms of ataxia with multiple system atrophy of cerebellar predominance (MSA-C), cortical cerebellar atrophy (CCA), and hereditary ataxias including SCA31 was evaluated by using audiogram and brainstem auditory evoked potentials (BAEPs). Results: Genetic analysis of dominant ataxia families revealed that a frequency of SCA31 in our cohort was fewer than that reported from other areas of Japan, indicating that SCA31 is not widely distributed throughout Japan. Results of audiogram showed no significant difference of hearing levels among ataxic groups, and those of BAEPs did not support inner ear dysfunction in SCA31 in which hearing loss had initially been suggested as one of its characteristic symptoms. Conclusion: This study suggests that acoustic impairment is neither specific to SCA31, MSA-C and CCA nor useful in making a differential diagnosis among them.
  • Hiromi Kawai, Shoko Deguchi, Kentaro Deguchi, Toru Yamashita, Yasuyuki Ohta, Yoshio Omote, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Brain research 1382 308 - 14 2011年03月 [査読有り][通常論文]
     
    Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28days, and physical and serum parameters were analyzed, then 90min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.
  • Tomoko Kurata, Kazunori Miyazaki, Miki Kozuki, Violeta-Lukic Panin, Nobutoshi Morimoto, Yasuyuki Ohta, Makiko Nagai, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Brain Research 1371 161 - 170 2011年01月 [査読有り][通常論文]
     
    In addition to simply reducing the serum level of cholesterol, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have various pleiotrophic effects such as reducing oxidative stress, neuroinflammation, and neurotoxicity. However, such a pleiotrophic effect has not been fully studied in a new statin (pitavastatin). We examined and compared the effects of two strong statins (atorvastatin, 30 mg/kg/day, p.o. pitavastatin, 3 mg/kg/day, p.o.) on the serum level of lipids, cognitive dysfunction, senile plaque (SP) and phosphorylated tau-positive dystrophic neuritis (pτDN) in amyloid precursor protein (APP) transgenic (Tg) mice from 5 months (M) of age to 20 M. These two statins improved behavioral memory and reduced the numbers of SP and pτDN at 15 and 20 M without affecting serum lipid levels, but preserved mice brain weight in pitavastatin group at 20 M. These protective effects of statins took 10 M from the beginning of treatment to show an improvement in the present model mice, and sensitivity to the statin treatment was linked to behavioral memory, SP and pτDN in this order. These findings suggest that early treatment with both atorvastatin and pitavastatin prevented subsequent worsening of cognitive function and the amyloidogenic process, probably due to pleiotrophic effects, suggesting a therapeutic potential for Alzheimer's disease (AD). © 2010 Elsevier B.V. All rights reserved.
  • Hiromi Kawai, Shoko Deguchi, Kentaro Deguchi, Toru Yamashita, Yasuyuki Ohta, Jingwei Shang, Fengfeng Tian, Xuemei Zhang, Ning Liu, Wentao Liu, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Brain research 1368 317 - 23 2011年01月 [査読有り][通常論文]
     
    Stroke is a major neurologic disorder and a leading cause of death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat after 90 min of transient middle cerebral artery occlusion (tMCAO). The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and at 24h of tMCAO, infarct volume and immunohistochemical analyses were performed. The combination of AM plus AT treatment decreased the infarct volume stronger than each single treatment with AM or AT. The numbers of positive cells of oxidative stress markers such as 8-hydroxy-2'-deoxyguanosin (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), and advanced end glycation products (AGE) and inflammation markers such as tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1(MCP-1) decreased dramatically in the combination-treated group compared with single AM- or AT-treated group. The present study showed that single AM or AT treatment showed neuroprotective effects both with antioxidative and anti-inflammatory mechanisms, but combination therapy of AM plus AT presented a further synergistic benefit in acute ischemic neural damages.
  • Yasuyuki Ohta, Makiko Nagai, Kazunori Miyazaki, Nobuhito Tanaka, Hiromi Kawai, Takafumi Mimoto, Nobutoshi Morimoto, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    CELL TRANSPLANTATION 20 10 1657 - 1657 2011年 [査読有り][通常論文]
  • Jingwei Shang, Kentaro Deguchi, Yasuyuki Ohta, Ning Liu, Xuemei Zhang, Fengfeng Tian, Toru Yamashita, Yoshio Ikeda, Tohru Matsuura, Hiroshi Funakoshi, Toshikazu Nakamura, Koji Abe
    Journal of neuroscience research 89 1 86 - 95 2011年01月 [査読有り][通常論文]
     
    Hepatocyte growth factor (HGF) and glial cell line-derived neurotrophic factor (GDNF) are strong neurotrophic factors. However, their potentials in neurogenesis, angiogenesis, synaptogenesis, and antifibrosis have not been compared. Therefore, we investigated these effects of HGF and GDNF in cerebral ischemia in the rat. Wistar rats were subjected to 90 min of transient middle cerebral artery occlusion (tMCAO). Immediately after reperfusion, HGF or GDNF was given by topical application. BrdU was injected intraperitoneally twice daily 1, 2, and 3 days after tMCAO. On 14 day, we histologically evaluated infarct volume, antiapoptotic effect, neurogenesis, angiogenesis, synaptogenesis, and antifibrosis. Both HGF and GDNF significantly reduced infarct size and the number of TUNEL-positive cells, but only HGF significantly increased the number of BrdU-positive cells in the subventricular zone, and 5'-bromo-2'-deoxyuridine -positive cells differentiated into mature neurons on the ischemic side. Enhancement of angiogenesis and synaptogenesis at the ischemic boundary zone was also observed only in HGF-treated rats. HGF significantly decreased the glial scar formation and scar thickness of the brain pia mater after tMCAO, but GDNF did not. Our study shows that both HGF and GDNF had significant neurotrophic effects, but only HGF can promote the neurogenesis, angiogenesis, and synaptogenesis and inhibit fibrotic change in brains after tMCAO.
  • Ohta Y, Nagai M, Miyazaki K, Tanaka N, Kawai H, Mimoto T, Morimoto N, Kurata T, Ikeda Y, Matsuura T, Abe K
    Cell medicine 2 2 69 - 83 2011年 [査読有り][通常論文]
     
    Bone marrow (BM) cells from amyotrophic lateral sclerosis (ALS) patients show significantly reduced expression of several neurotrophic factors. Monotherapy with either wild-type (WT) BM transplantation (BMT) or granulocyte colony-stimulating factor (GCSF) has only a small clinical therapeutic effect in an ALS mouse model, due to the phenomenon of neuroprotection. In this study, we investigated the clinical benefits of combination therapy using BMT with WT BM cells, plus GCSF after disease onset in ALS mice [transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation]. Combined treatment with BMT and GCSF delayed disease progression and prolonged the survival of G93A mice, whereas BMT or GCSF treatment alone did not. Histological study of the ventral horns of lumbar cords from G93A mice treated with BMT and GCSF showed a reduction in motor neuron loss coupled with induced neuronal precursor cell proliferation, increased expression of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor and angiogenin), and neovascularization compared with controls (vehicle only). Compared with G93A microglial cells, most BM-derived WT cells differentiated into microglial cells and strongly expressed neurotrophic factors, combined BMT and GCSF treatment led to the replacement of G93A microglial cells with BM-derived WT cells. These results indicate combined treatment with BMT and GCSF has potential neuroprotective and angiogenic effects in ALS mice, induced by the replacement of G93A microglial cells with BM-derived WT cells. Furthermore, this is the first report showing the effects of combined BMT and GCSF treatment on blood vessels in ALS.
  • ALS患者における栄養管理と生命予後
    永井 真貴子, 森本 展年, 出口 健太郎, 名古谷 章子, 太田 康之, 武久 康, 池田 佳生, 松浦 徹, 阿部 康二
    臨床神経学 50 12 1198 - 1198 (一社)日本神経学会 2010年12月
  • TAT-FNK蛋白髄腔内投与によるALSモデルマウスへの蛋白治療の開発
    太田 康之, 永井 真貴子, 森本 展年, 宮崎 一徳, 武久 康, 倉田 智子, 池田 佳生, 松浦 徹, 麻生 貞光, 太田 成男, 阿部 康二
    臨床神経学 50 12 1231 - 1231 (一社)日本神経学会 2010年12月
  • Ning Liu, Kentaro Deguchi, Jingwei Shang, Xuemei Zhang, Fengfeng Tian, Toru Yamashita, Yasuyuki Ohta, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Journal of neuroscience research 88 16 3488 - 97 2010年12月 [査読有り][通常論文]
     
    Apoptosis is one of the mechanisms contributing to neuronal degeneration in ischemic stroke. In vivo imaging of annexin V (A5) was performed at 12 hr, 24 hr, 48 hr, and 4 days after 90-min transient middle cerebral artery occlusion (tMCAO) in mice with a fluorescent protein Cy5.5. Immunohistochemistry for heat shock protein 70 (HSP70), A5, and TUNEL were also performed with brain sections after the tMCAO. In vivo fluorescence was strongly observed at 48 hr over the head, especially with removal of both head skin and skull bone. Zonal ex vivo fluorescent signals were surrounding the ischemic core, and double-positive cells with Cy5.5/exogenous A5 antibody were found in this area. HSP70 was observed at the peak time of 24 hr; A5 became detectable at 12 hr, with increasing numbers until 48 hr. The number of TUNEL-positive cells increased at 24 hr and retained the high level until 4 days, showing a dissociating temporal pattern with A5. Double-positive cells for A5/TUNEL reached their peak at 48 hr. All the data suggest that some cells still have a chance to be rescued for a long period after acute cerebral ischemia. The in vivo Cy5.5 fluorescence representing A5 signal spatially surrounding the ischemic core temporally detects an early-stage apoptosis after cerebral ischemia.
  • マウス虚血脳での移植iPS細胞の解析
    河相 裕美, 山下 徹, 太田 康之, 出口 健太郎, 出口 章子, 張 雪梅, 池田 佳生, 松浦 徹, 阿部 康二
    脳循環代謝 22 1 127 - 127 (一社)日本脳循環代謝学会 2010年11月
  • FengFeng Tian, Kentaro Deguchi, Toru Yamashita, Yasuyuki Ohta, Nobutoshi Morimoto, Jingwei Shang, Xuemei Zhang, Ning Liu, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Autophagy 6 8 1107 - 14 2010年11月 [査読有り][通常論文]
     
    Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (Tg) mice, in vivo imaging of autophagy was performed at 1, 3 and 6 d after 60 min transient middle cerebral artery occlusion (tMCAO). Ex vivo imaging of autophagy, testing of the autophagy inhibitor 3-methyladenine (3-MA), estern blot analysis, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and fluorescent analyses were performed on brain sections following tMCAO. In vivo fluorescent signals were detected above the ischemic hemisphere through the skull bone at 1, 3 and 6 d after tMCAO, with a peak at 1 d. Similar results were obtained with ex vivo fluorescence imaging. western blot analysis revealed maximum LC3-I and LC3-II expression at 1 d after tMCAO and fluorescence immunohistochemistry demonstrated that GFP-LC3-positive cells were primarily neuronal, not astroglial or microglial, cells. The number of GFP-LC3/TUNEL double-positive cells was greater in the periischemic area than in the core. These results provided evidence of in vivo autophagy detection, with a peak at 1 d, in a live animal model following cerebral ischemia. This novel technique could be valuable for monitoring autophagic processes in vivo in live stroke patients, as well as for clarifying the detailed role of autophagy in the ischemic brain, as well as in other neurological diseases.
  • 進行性核上性麻痺と純粋無動症における臨床画像的検討
    倉田 智子, 宮崎 一徳, 森本 展年, 太田 康之, 瓦林 毅, 高尾 芳樹, 大田 泰正, 針谷 康夫, 真邊 泰宏, 池田 佳生, 松浦 徹, 東海林 幹夫, 阿部 康二
    日本神経心理学会総会プログラム・予稿集 34回 136 - 136 日本神経心理学会 2010年08月
  • ALSモデルマウス腰髄におけるNogo-AとそのレセプターであるNgRの変化(Changes of Nogo-A and receptor NgR in the lumbar spinal cord of ALS model mice)
    宮崎 一徳, 永井 真貴子, 森本 展年, 倉田 智子, 太田 康之, 武久 康, 池田 佳生, 松浦 徹, 阿部 康二
    神経化学 49 2-3 505 - 505 2010年08月
  • マウス虚血脳へのiPS細胞移植(Induced pluripotent stem cells transplanted in mouse Ischemic brain)
    河相 裕美, 山下 徹, 太田 康之, 出口 健太郎, 出口 章子, 張 雪梅, 池田 佳生, 松浦 徹, 阿部 康二
    神経化学 49 2-3 707 - 707 2010年08月
  • Jingwei Shang, Kentaro Deguchi, Toru Yamashita, Yasuyuki Ohta, Hanzhe Zhang, Nobutoshi Morimoto, Ning Liu, Xuemei Zhang, Fengfeng Tian, Tohru Matsuura, Hiroshi Funakoshi, Toshikazu Nakamura, Koji Abe
    JOURNAL OF NEUROSCIENCE RESEARCH 88 10 2197 - 2206 2010年08月 [査読有り][通常論文]
     
    Glial cell line-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF) are strong neurotrophic factors, which function as antiapoptotic factors. However, the neuroprotective effect of GDNF and HGF in ameliorating ischemic brain injury via an antiautophagic effect has not been examined. Therefore, we investigated GDNF and HGF for changes of infarct size and antiapoptotic and antiautophagic effects after transient middle cerebral artery occlusion (tMCAO) in rats. For the estimation of ischemic brain injury, the infarct size was calculated at 24 hr after tMCAO by HE staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed for evaluating the antiapoptotic effect. Western blot analysis of microtubule-associated protein 1 light chain 3 (LC3) and immunofluorescence analysis of LC3 and phosphorylated niTOR/Ser(2448) (p-mTOR) were performed for evaluating the antiautophagic effect. GDNF and HGF significantly reduced infarct size after cerebral ischemia. The amounts of LC3-I plus LC3-II (relative to p-tubulin) were significantly increased after tMCAO, and GDNF and HGF significantly decreased them. GDNF and HGF significantly increased p-mTOR-positive cells. GDNF and HGF significantly decreased the numbers of TUNEL-, LC3-, and LC3/TUNEL double-positive cells. LC3/TUNEL double-positive cells accounted for about 34.3% of LC3 plus TUNEL-positive cells. This study suggests that the protective effects of GDNF and HGF were greatly associated with not only the antiapoptotic but also the antiautophagic effects; maybe two types of cell death can occur in the same cell at the same time, and GDNF and HGF are capable of ameliorating these two pathways. (C) 2010 Wiley-Liss, Inc.
  • Hiromi Kawai, Toru Yamashita, Yasuyuki Ohta, Kentaro Deguchi, Shoko Nagotani, Xuemei Zhang, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 30 8 1487 - 1493 2010年08月 [査読有り][通常論文]
     
    Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5x10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1487-1493; doi: 10.1038/jcbfm.2010.32; published online 10 March 2010
  • Xuemei Zhang, Kentaro Deguchi, Toru Yamashita, Yasuyuki Ohta, Jingwei Shang, Fengfeng Tian, Ning Liu, Violeta Lukic Panin, Yoshio Ikeda, Tohru Matsuura, Koji Abe
    Brain research 1343 143 - 52 2010年07月 [査読有り][通常論文]
     
    Temporal and spatial differences and relationships of proteins relating to the ischemic penumbra were examined at 1, 3, 12, 24, and 48 h after 90 min of transient middle cerebral artery occlusion (tMCAO) in rats. 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that the apparent infarction focus first appeared at 1h after tMCAO, which then largely matured at 24h. Immunohistochemistry and Western blot indicated no or trace levels of c-fos, hypoxia inducible factor-1 alpha (HIF-1 alpha), heat shock protein 70 (HSP70), and annexin V (A5) positive cells in the sham control brain. Expression of c-fos increased quickly and widely within and outside of the affected arterial territory (peak at 1h), and that of HIF-1 alpha reached the maximum at 12h in a smaller area than c-fos. HSP70 began to be induced during the first few hours after tMCAO, peaked at 24h, then decreased within 48 h, while A5 was slightly expressed at 3h, then gradually increased until 48 h. Double immunofluorescent analyses showed that the colocalization rates of c-fos/HIF-1 alpha, HIF-1 alpha/HSP70, HSP70/A5, and A5/TUNEL were 40.6%, 58.4%, 42.1% and 61.0%, respectively. These data suggest that multiple molecular penumbra exist after 90 min of tMCAO in the rat brain where several different proteins participate in different temporal and spatial expression patterns. Thus, there is a window for rescue of ischemic neural cells from 12 to 48 h after injury.
  • 河野 祥一郎, 出口 健太郎, 名古谷 章子, 倉田 智子, 太田 康之, 池田 佳生, 松浦 徹, 阿部 康二, 伊藤 浩, 赤木 禎治
    Neurosonology 23 増刊 67 - 67 (一社)日本脳神経超音波学会 2010年06月
  • Nobutoshi Morimoto, Makiko Nagai, Kazunori Miyazaki, Yasuyuki Ohta, Tomoko Kurata, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Masato Asanuma, Koji Abe
    JOURNAL OF NEUROSCIENCE RESEARCH 88 8 1804 - 1811 2010年06月 [査読有り][通常論文]
     
    Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression increased in the spinal motor neurons. The activated form of p53 also increased and translocated to the nuclei of spinal motor neurons, followed by increased expression of p53-activated gene 608 (PAG608). This is the first report demonstrating that increased expression of PAG608 correlates with activation of phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis model. These results provide further evidence of the profound correlations between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism-related proteins. (C) 2010 Wiley-Liss, Inc.
  • 運動ニューロンのエイジングを示すALSモデルマウス脊髄前角の再生環境
    宮崎 一徳, 永井 真貴子, 森本 展年, 倉田 智子, 太田 康之, 武久 康, 池田 佳生, 松浦 徹, 阿部 康二
    日本抗加齢医学会総会プログラム・抄録集 10回 255 - 255 (一社)日本抗加齢医学会 2010年05月
  • 池田 佳生, 辻 徳生, 折戸 謙介, 松浦 徹, 石井 抱, 阿部 康二
    神経治療学 27 3 439 - 439 (一社)日本神経治療学会 2010年05月 [査読有り][通常論文]
  • Tohru Matsuura
    Clinical Neurology 50 11 984  2010年 [査読有り][通常論文]
  • Tatsuaki Kurosaki, Tohru Matsuura, Kinji Ohno, Shintaroh Ueda
    MOLECULAR BIOLOGY AND EVOLUTION 26 11 2573 - 2579 2009年11月 [査読有り][通常論文]
     
    Spinocerebellar ataxia type 10 is caused by ATTCT repeat expansion in the ATXN10 gene in humans. We studied the evolutionary history of the human genome to determine the time and mechanism of the acquisition of unstable ATTCT repeats in the genome. We found that long interspersed element-1 (LINE-1) was inserted into ATXN10 intron 9; Alu was then inserted in the middle of LINE-1; and endogenous retrovilcus K was lastly retrotransposed in the middle of Alu. The ATTCT repeat was located on the boundary between the 3'-end of the Alu element and the direct repeat arising from LINE-1. We determined nucleotide sequences of the orthologous region of 50 individuals representing 33 primate species and compared them with the human sequence. The analysis revealed that the ATTCT repeat is present only in human and apes. Old World monkeys also possess pentanucleotide repeats, but their motifs are TGTCT and GGTCT. New World monkeys and prosimians are not informative because they lack the corresponding region in ATXN10 intron 9. Our studies dictate two parsimonious scenarios of evolution. First, a TT (C) under barT motif arose from a TTTTT motif at the junction of Alu and LINE-1, which was followed by introduction of A to make an (A) under bar TTCT motif in horminoids. Second, an ATT (C) under barT motif wits directly generated from an ancestral ATM motif in the common ancestor of catarrhines. We also demonstrate that orangutan uniquely introduced G to make a (G) under bar TTCT motif and later C to make a GTTC (C) under bar motif, where newly introduced nucleotides are underlined. Our Studies reveal that nucleotide substitutions in a poly(A) tail of the Alu element and the following amplification of pentanucleotides occurred in the lineages of Old World monkeys and hominoids and that unstable ATTCT pentanucleotide repeats originated in the common ancestor of hominoids. These findings also highlight a new aspect of the role of retrotransposons in human disease and evolution, which might be useful in investigating the mystery of human uniqueness.
  • Nozomu Sato, Takeshi Amino, Kazuhiro Kobayashi, Shuichi Asakawa, Taro Ishiguro, Taiji Tsunemi, Makoto Takahashi, Tohru Matsuura, Kevin M. Flanigan, Sawa Iwasaki, Fumitoshi Ishino, Yuko Saito, Shigeo Murayama, Mari Yoshida, Yoshio Hashizume, Yuji Takahashi, Shoji Tsuji, Nobuyoshi Shimizu, Tatsushi Toda, Kinya Ishikawa, Hidehiro Mizusawa
    AMERICAN JOURNAL OF HUMAN GENETICS 85 5 544 - 557 2009年11月 [査読有り][通常論文]
     
    Spinocerebellar ataxia type 31 (SCA31) is an adult-onset autosomal-dominant neurodegenerative disorder showing progressive cerebellar ataxia mainly affecting Purkinje cells. The SCA31 critical region was tracked down to a 900 kb interval in chromosome 16q22.1, where the disease shows a strong founder effect. By performing comprehensive Southern blot analysis and BAC- and fosmid-based sequencing, we isolated two genetic changes segregating with SCA31. One was a single-nucleotide change in an intron of the thymidine kinase 2 gene (TK2). However, this did not appear to affect splicing or expression patterns. The other was an insertion, from 2.5-3.8 kb long, consisting of complex penta-nucleotide repeats including a long (TGGAA)(n) stretch. In controls, shorter (1.5-2.0 kb) insertions lacking (TGGAA)(n) were found only rarely. The SCA31 repeat insertion's length inversely correlated with patient age of onset, and an expansion was documented in a single family showing anticipation. The repeat insertion was located in introns of TK2 and BEAN (brain expressed, associated with Nedd4) expressed in the brain and formed RNA foci in the nuclei of patients' Purkinje cells. An electrophoretic mobility-shift assay showed that essential splicing factors, serine/arginine-rich splicing factors SFRS1 and SFRS9, bind to (UGGAA)(n) in vitro. Because (TGGAA)(n) is a characteristic sequence of paracentromeric heterochromatin, we speculate that the insertion might have originated from heterochromatin. SCA31 is important because it exemplifies human diseases associated with "inserted" microsatellite repeats that can expand through transmission. Our finding suggests that the ectopic microsatellite repeat, when transcribed, might cause a disease involving the essential splicing factors.
  • 本邦のCADASIL 7家系に於ける頭部MRI画像所見の特徴
    高宮 資宜, 表 芳夫, 太田 康之, 名古谷 章子, 出口 健太郎, 武久 康, 松浦 徹, 阿部 康二
    Dementia Japan 23 2 249 - 249 (一社)日本認知症学会 2009年08月
  • Katharine A. Hagerman, Haihe Ruan, Kerrie Nichol Edamura, Tohru Matsuura, Christopher E. Pearson, Yuh-Hwa Wang
    GENE 434 1-2 29 - 34 2009年04月 [査読無し][通常論文]
     
    Nucleosome packaging influences many aspects of DNA metabolism such as replication, repair and transcription, and via this link likely has further downstream effects on genome stability. The instability and expansion of repetitive sequences is associated with at least 42 human diseases yet the molecular conditions, contributing to repeat instability have remained largely undetermined. Previously we showed strong nucleosome formation on CAG repeats associated with spinocerebellar ataxia type 1 and very weak formation on CGG repeats associated with fragile X syndrome, and that interruption of these repeat tracts made the DNA behave more like random sequences. In this study, we determined nucleosome formation on pure and interrupted ATTCT pentanucleotides associated with spinocerebellar ataxia type 10 (SCA10). We report strong nucleosome formation on ATTCT repeats, like CAG tracts. Surprisingly, in contrast to the effect of interruptions on other repeat sequences, interruptions in the expanded ATTCT tracts further strengthened assembly with hyperacetylated histones under physiological conditions with NAP-1. These differences may contribute to phenotypic variation seen between families having pure and interrupted SCA10 repeats as well, as the overall genetic instability at the SCA10 locus. (c) 2008 Elsevier B.V. All rights reserved.
  • Yang Bian, Akio Masuda, Tohru Matsuura, Mikako Ito, Kazuya Okushin, Andrew G. Engel, Kinji Ohno
    HUMAN MOLECULAR GENETICS 18 7 1229 - 1237 2009年04月 [査読有り][通常論文]
     
    We recently reported that the intronic splice-site mutation IVS3-8G > A of CHRNA1 that encodes the muscle nicotinic acetylcholine receptor alpha subunit disrupts binding of a splicing repressor, hnRNP H. This, in turn, results in exclusive inclusion of the downstream exon P3A. The P3A(+) transcript encodes a non-functional alpha subunit that comprises 50% of the transcripts in normal human skeletal muscle, but its functional significance remains undetermined. In an effort to search for a potential therapy, we screened off-label effects of 960 bioactive chemical compounds and found that tannic acid ameliorates the aberrant splicing due to IVS3-8G > A but without altering the expression of hnRNP H. Therefore, we searched for another splicing trans-factor. We found that the polypyrimidine tract binding protein (PTB) binds close to the 3' end of CHRNA1 intron 3, that PTB induces skipping of exon P3A and that tannic acid increases the expression of PTB in a dose-dependent manner. Deletion assays of the PTB promoter region revealed that the tannic acid-responsive element is between positions -232 and -74 from the translation initiation site. These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression.
  • Teresa Almeida, Isabel Alonso, Sandra Martins, Eliana Marisa Ramos, Luisa Azevedo, Kinji Ohno, Antonio Amorim, Maria Luiza Saraiva-Pereira, Laura Bannach Jardim, Tohru Matsuura, Jorge Sequeiros, Isabel Silveira
    PLOS ONE 4 2 e4553  2009年02月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil.
  • Akio Masuda, Xin-Ming Shen, Mikako Ito, Tohru Matsuura, Andrew G. Engel, Kinji Ohno
    HUMAN MOLECULAR GENETICS 17 24 4022 - 4035 2008年12月 [査読無し][通常論文]
     
    In humans and great apes, CHRNA1 encoding the muscle nicotinic acetylcholine receptor alpha subunit carries an inframe exon P3A, the inclusion of which yields a nonfunctional alpha subunit. In muscle, the P3A(-) and P3A(+) transcripts are generated in a 1:1 ratio but the functional significance and regulation of the alternative splicing remain elusive. An intronic mutation (IVS3-8G > A), identified in a patient with congenital myasthenic syndrome, disrupts an intronic splicing silencer (ISS) and results in exclusive inclusion of the downstream P3A exon. We found that the ISS-binding splicing trans-factor was heterogeneous nuclear ribonucleoprotein (hnRNP) H and the mutation attenuated the affinity of hnRNP for the ISS similar to 100-fold. We next showed that direct placement of hnRNP H to the 3' end of intron 3 silences, and siRNA-mediated downregulation of hnRNP H enhances recognition of exon P3A. Analysis of the human genome suggested that the hnRNPH-binding UGGG motif is overrepresented close to the 3' ends of introns. Pursuing this clue, we showed that alternative exons of GRIP1, FAS, VPS13C and NRCAM are downregulated by hnRNP H. Our findings imply that the presence of the hnRNP H-binding motif close to the 3' end of an intron is an essential but underestimated splicing regulator of the downstream exon.
  • Tatsuaki Kurosaki, Tohru Matsuura, Kinji Ohno, Shintaroh Ueda
    NEUROGENETICS 9 2 151 - 152 2008年05月 [査読無し][通常論文]
  • Kaiping Gao, Akio Masuda, Tohru Matsuura, Kinji Ohno
    NUCLEIC ACIDS RESEARCH 36 7 2257 - 2267 2008年04月 [査読無し][通常論文]
     
    Yeast carries a strictly conserved branch point sequence (BPS) of UACUA (A) under barC, whereas the human BPS is degenerative and is less well characterized. The human consensus BPS has never been extensively explored in vitro to date. Here, we sequenced 367 clones of lariat RT-PCR products arising from 52 introns of 20 human housekeeping genes. Among the 367 clones, a misincorporated nucleotide at the branch point was observed in 181 clones, for which we can precisely pinpoint the branch point. The branch points were comprised of 92.3 A, 3.3 C, 1.7 G and 2.8 U. Our analysis revealed that the human consensus BPS is simply yUn (A) under bary, where the underlined is the branch point at position zero and the lowercase pyrimidines ('y') are not as well conserved as the uppercase U and A. We found that the branch points are located 2134 nucleotides upstream of the 3' end of an intron in 83 clones. We also found that the polypyrimidine tract spans 424 nucleotides downstream of the branch point. Our analysis demonstrates that the human BPSs are more degenerative than we have expected and that the human BPSs are likely to be recognized in combination with the polypyrimidine tract and/or the other splicing cis-elements.
  • Rui Gao, Tohru Matsuura, Mary Coolbaugh, Christine Zuehlke, Koichiro Nakamura, Astrid Rasmussen, Michael J. Siciliano, Tetsuo Ashizawa, Xi Lin
    EUROPEAN JOURNAL OF HUMAN GENETICS 16 2 215 - 222 2008年02月 [査読無し][通常論文]
     
    Trinucleotide repeat expansions are dynamic mutations causing many neurological disorders, and their instability is influenced by multiple factors. Repeat configuration seems particularly important, and pure repeats are thought to be more unstable than interrupted repeats. But direct evidence is still lacking. Here, we presented strong support for this hypothesis from our studies on spinocerebellar ataxia type 17 (SCA17). SCA17 is a typical polyglutamine disease caused by CAG repeat expansion in TBP (TATA binding protein), and is unique in that the pure expanded polyglutamine tract is coded by either a simple configuration with long stretches of pure CAGs or a complex configuration containing CAA interruptions. By small pool PCR (SP-PCR) analysis of blood DNA from SCA17 patients of distinct racial backgrounds, we quantitatively assessed the instability of these two types of expanded alleles coding similar length of polyglutamine expansion. Mutation frequency in patients harboring pure CAG repeats is 2-3 folds of those with CAA interruptions. Interestingly, the pure CAG repeats showed both expansion and deletion while the interrupted repeats exhibited mostly deletion at a significantly lower frequency. These data strongly suggest that repeat configuration is a critical determinant for instability, and CAA interruptions might serve as a limiting element for further expansion of CAG repeats in SCA17 locus, suggesting a molecular basis for lack of anticipation in SCA17 families with interrupted CAG expansion.
  • Tsukasa Saito, Yoshinobu Amakusa, Takashi Kimura, Osamu Yahara, Hitoshi Aizawa, Yoshio Ikeda, John W. Day, Laura P. W. Ranum, Kinji Ohno, Tohru Matsuura
    NEUROGENETICS 9 1 61 - 63 2008年02月 [査読無し][通常論文]
     
    Myotonic dystrophy type 2 (DM2) is caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3q21. All studied DM2 mutations have been reported in Caucasians and share an identical haplotype, suggesting a common founder. We identified a Japanese patient with DM2 and showed that the affected haplotype is distinct from the previously identified DM2 haplotype shared among Caucasians. These data strongly suggest that DM2 expansion mutations originate from separate founders in Europe and Japan and are more widely distributed than previously recognized.
  • Matsuura T
    Rinsho shinkeigaku = Clinical neurology 48 1 1 - 10 2008年01月 [査読有り][通常論文]
  • Tohru Matsuura
    Clinical Neurology 48 11 823 - 825 2008年 [査読有り][通常論文]
     
    Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited neurodegenerative disease caused by expansion of the ATTCT pentanucleotide repeat in intron 9 of a novel gene, ATXN10, on chromosome 22q13.3. It is clinically characterized by progressive ataxia, seizures, and anticipation, which can vary within and between families. The length of the expanded ATTCT repeats is highly unstable on paternal transmission and shows a variable degree of somatic and germline instabilty, revealing complex SCA10 genetic mechanisms. How this untranslated ATTCT expansion leads to neurodegeneration has been still controversial. Growing number of evidence indicates a gain-of-function RNA mechanism, similar to the myotonic dystrophies caused by non-coding CTG or CCTG repeat expansions.
  • Kentaro Sahashi, Akio Masuda, Tohru Matsuura, Jun Shinmi, Zhujun Zhang, Yasuhiro Takeshima, Masafumi Matsuo, Gen Sobue, Kinji Ohno
    NUCLEIC ACIDS RESEARCH 35 18 5995 - 6003 2007年09月 [査読無し][通常論文]
     
    We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5' splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189 249 U2-dependent 5' splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5' splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (R-i) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity=97.1%) and normal splicings in 36 of 38 sites (specificity=94.7%). Simulation of all possible exonic mutations at positions -3, -2 and -1 of the 189249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5' splice site.
  • Masatoshi Ichihara, Yoshiki Murakumo, Akio Masuda, Toru Matsuura, Naoya Asai, Mayumi Jijiwa, Maki Ishida, Jun Shinmi, Hiroshi Yatsuya, Shanlou Qiao, Masahide Takahashi, Kinji Ohno
    NUCLEIC ACIDS RESEARCH 35 18 e123  2007年09月 [査読無し][通常論文]
     
    We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (Delta G) is less than 34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole Delta G value in designing siRNAs.
  • M. Wakamiya, T. Matsuura, Y. Liu, G. C. Schuster, R. Gao, W. Xu, P. S. Sarkar, X. Lin, T. Ashizawa
    NEUROLOGY 67 4 607 - 613 2006年08月 [査読無し][通常論文]
     
    Background: Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. SCA10 is caused by an expansion of an ATTCT pentanucleotide repeat in intron 9 of the ataxin 10 (ATXN10) gene encoding an approximately 55-kd protein of unknown function. However, how this mutation leads to SCA10 is unknown. Methods: In an effort to understand the pathogenic mechanism of SCA10, the authors conducted a series of experiments to address the effect of repeat expansion on the transcription and RNA processing of the ATXN10 gene. In addition, we generated Sca10 (mouse ataxin 10 homolog)-null mice and addressed the role of Sca10 gene dosage on the cerebellum. Results: Mutant ATXN10 allele is transcribed at the normal level, and the pre-mRNA containing an expanded repeat is processed normally in patient-derived cells. Sca10-null mice exhibited embryonic lethality. Heterozygous mutants were overtly normal and did not develop SCA10 phenotype Conclusion: A simple gain of function or loss of function of ATXN10 is unlikely to be the major pathogenic mechanism contributing to the spinocerebellar ataxia type 10 phenotype.
  • Alonso, I, LB Jardim, O Artigalas, ML Saraiva-Pereira, T Matsuura, T Ashizawa, J Sequeiros, Silveira, I
    NEUROLOGY 66 10 1602 - 1604 2006年05月 [査読無し][通常論文]
  • T Matsuura, P Fang, CE Pearson, P Jayakar, T Ashizawa, BB Roa, DL Nelson
    AMERICAN JOURNAL OF HUMAN GENETICS 78 1 125 - 129 2006年01月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 10 ( SCA10) is one of numerous genetic disorders that result from simple repeat expansions. SCA10 is caused by expansion of an intronic ATTCT pentanucleotide repeat tract. It is clinically characterized by progressive ataxia, seizures, and anticipation, which can vary within and between families. We report two SCA10 families showing distinct frequencies of seizures and correlations of repeat length with age at onset. One family displayed uninterrupted ATTCT expansions, whereas the other showed multiple interruptions of the repeat by nonconsensus repeat units, which differed both in the length and/ or sequence of the repeat unit. Disease-causing microsatellite expansions have been assumed to be composed of uninterrupted pure repeats. Our findings for SCA10 challenge this convention and suggest that the purity of the expanded repeat element may be a disease modifier.
  • AI Seixas, MH Maurer, M Lin, C Callahan, A Ahuja, T Matsuura, CA Ross, FM Hisama, Silveira, I, RL Margolis
    AMERICAN JOURNAL OF MEDICAL GENETICS PART A 136A 1 87 - 89 2005年07月 [査読無し][通常論文]
  • S Buervenich, A Carmine, D Galter, HN Shahabi, B Johnels, B Holmberg, J Ahlberg, H Nissbrandt, J Eerola, O Hellstrom, P Tienari, T Matsuura, T Ashizawa, U Wullner, T Klockgether, A Zimprich, T Gasser, M Hanson, S Waseem, A Singleton, FJ McMahon, M Anvret, O Sydow, L Olson
    Arch Neurol 62 1 74 - 78 2005年01月 [査読無し][通常論文]
     
    Background: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. Patients: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. Results: The previously identified association with an ADH class IV allele remained significant (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PD patients but only in 6 controls (0.6%). This association was statistically significant (x(1)(2) = 7.5; 2-sided P=.007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. Conclusion: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.
  • T Matsuura, P Fang, Lin, X, M Khajavi, K Tsuji, A Rasmussen, RP Grewal, M Achari, ME Alonso, SM Pulst, HY Zoghbi, DL Nelson, BB Roa, T Ashizawa
    AMERICAN JOURNAL OF HUMAN GENETICS 74 6 1216 - 1224 2004年06月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by ataxia, seizures, and anticipation. It is caused by an expanded ATTCT pentanucleotide repeat in intron 9 of a novel gene, designated "SCA10." The ATTCT expansion in SCA10 represents a novel class of microsatellite repeat and is one of the largest found to cause human diseases. The expanded ATTCT repeat is unstably transmitted from generation to generation, and an inverse correlation has been observed between size of repeat and age at onset. In this multifamily study, we investigated the intergenerational instability, somatic and germline mosaicism, and age-dependent repeat-size changes of the expanded ATTCT repeat. Our results showed that (1) the expanded ATTCT repeats are highly unstable when paternally transmitted, whereas maternal transmission resulted in significantly smaller changes in repeat size; (2) blood leukocytes, lymphoblastoid cells, buccal cells, and sperm have a variable degree of mosaicism in ATTCT expansion; (3) the length of the expanded repeat was not observed to change in individuals over a 5-year period; and (4) clinically determined anticipation is sometimes associated with intergenerational contraction rather than expansion of the ATTCT repeat.
  • C Cagnoli, C Michielotto, T Matsuura, T Ashizawa, RL Margolis, SE Holmes, C Gellera, N Migone, A Brusco
    JOURNAL OF MOLECULAR DIAGNOSTICS 6 2 96 - 100 2004年05月 [査読無し][通常論文]
     
    At least 18 human genetic diseases are caused by expansion of short tandem repeats. Here we describe a successful application of a fluorescent PCR method for the detection of expanded repeats in FRDA1, SCA10, and SCA12 genes. Although this test cannot give a precise estimate of the size of the expansion, it is robust, reliable, and inexpensive, and can be used to screen large series of patients. it proved useful for confirming the presence of large expansions in the Friedreich ataxia gene following an ambiguous result of long-range PCR, as well as rapid pre-screening for large repeat expansions associated with Friedreich ataxia and SCA10 and the shorter repeat expansions associated with SCA12.
  • MA Knight, RJ McKinlay Gardner, M Bahlo, T Matsuura, JA Dixon, SM Forrest, E Storey
    BRAIN 127 1172 - 1181 2004年05月 [査読無し][通常論文]
     
    We describe a pedigree of Anglo-Celtic origin with a phenotypically unique form of dominantly inherited spinocerebellar ataxia (SCA) in 14 personally examined affected members. A remarkable observation is dentate nucleus calcification, producing a low signal on MRI sequences. Unusually for an SCA, dysarthria is typically the initial manifestation. Mild pyramidal signs and hypermetric saccades are noted in some. Its distinguishing clinical features, each present in a majority of affected persons, are palatal tremor, and a form of dysphonia resembling spasmodic dysphonia. Repeat expansion detection failed to identify either CAG/CTG or ATTCT/AGAAT repeat expansions segregating with the disease in this family. The testable SCA mutations have been excluded. On linkage analysis, the locus maps to chromosome 11, which rules out all the remaining mapped SCAs except for SCA5. While locus homogeneity with SCA5 is not formally excluded, we consider it rather unlikely on phenotypic grounds, and propose that this condition may represent an addition to the group of neurogenetic disorders subsumed under the rubric SCA. The International Nomenclature Committee has made a provisional assignment of 'SCA20', although firm designation will have to await a definite molecular distinction from SCA5.
  • RH Walker, A Rasmussen, D Rudnicki, SE Holmes, E Alonso, T Matsuura, T Ashizawa, B Davidoff-Feldman, RL Margolis
    Neurology 61 7 1002 - 1004 2003年10月 [査読無し][通常論文]
     
    Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.
  • MA Knight, ML Kennerson, RJ Anney, T Matsuura, GA Nicholson, P Salimi-Tari, RJM Gardner, E Storey, SM Forrest
    NEUROBIOLOGY OF DISEASE 13 2 147 - 157 2003年07月 [査読無し][通常論文]
     
    We have studied a large Australian kindred with a dominantly inherited pure cerebellar ataxia, SCA15. The disease is characterised by a very slow rate of progression in some family members, and atrophy predominantly of the superior vermis, and to a lesser extent the cerebellar hemispheres. Repeat expansion detection failed to identify either a CAG/CTG or ATTCT/AGAAT repeat expansions segregating with the disease in this family. A genome-wide scan revealed significant evidence for linkage to the short arm of chromosome 3. The highest two-point LOD score was obtained with D3S3706 (Z = 3.4, theta = 0.0). Haplotype analysis identified recombinants that placed the SCA15 locus within an 11.6-cM region flanked by the markers D3S3630 and D3S1304. The mouse syntenic region contains two ataxic mutants, itpr1(-/-) and opt, affecting the inositol 1,4,5-triphosphate type 1 receptor, ITPR1 gene. ITPR1 is predominantly expressed in the cerebellar Purkinje cells. Mutation analysis from two representative affected family members excluded the coding region of the ITPR1 gene from being involved in the pathogenesis of SCA 15. Thus, the itpr1(-/-) and opt ITPR1 mouse mutants, which each result in ataxia, are not allelic to the human SCA15 locus. (C) 2003 Elsevier Science (USA). All rights reserved.
  • VN Potaman, JJ Bissler, Hashem, VI, EA Oussatcheva, L Lu, LS Shlyakhtenko, YL Lyubchenko, T Matsuura, T Ashizawa, M Leffak, CJ Benham, RR Sinden
    JOURNAL OF MOLECULAR BIOLOGY 326 4 1095 - 1111 2003年02月 [査読無し][通常論文]
     
    A number of human hereditary diseases have been associated with the instability of DNA repeats in the genome. Recently, spinocerebellar ataxia type 10 has been associated with expansion of the pentanucleotide repeat (ATTCT)(n).(AGAAT)(n) from a normal range of ten to 22 to as many as 4500 copies. The structural properties of this repeat cloned in circular plasmids were studied by a variety of methods. Two-dimensional gel electrophoresis and atomic force microscopy detected local DNA unpairing in supercoiled plasmids. Chemical probing analysis indicated that, at moderate superhelical densities, the (ATTCT),.(AGAAT),, repeat forms an unpaired region, which further extends into adjacent A + T-rich flanking sequences at higher superhelical densities. The superhelical energy required to initiate duplex unpairing is essentially length-independent from eight to 46 repeats. In plasmids containing five repeats, minimal unpairing of (ATTCT)(5).(AGAAT)(5) occurred while 2D gel analysis and chemical probing indicate greater unpairing in A + T-rich sequences in other regions of the plasmid. The observed experimental results are consistent with a statistical mechanical, computational analysis of these supercoiled plasmids. For plasmids containing 29 repeats, which is just above the normal human size range, flanked by an A + T-rich sequence, atomic force microscopy detected the formation of a locally condensed structure at high superhelical densities. However, even at high superhelical densities, DNA strands within the presumably compact A + T-rich region were accessible to small chemicals and oligonucleotide hybridization. Thus, DNA strands in this "collapsed structure" remain unpaired and accessible for interaction with other molecules. The unpaired DNA structure functioned as an aberrant replication origin, in that it supported complete plasmid replication in a HeLa cell extract. A model is proposed in which unscheduled or aberrant DNA replication is a critical step in the expansion mutation. (C) 2003 Elsevier Science Ltd. All rights reserved.
  • Neurophysiological findings in SPG4 are variable, dependent on the type of spastin mutation.
    Neurology e-letters  2003年 [査読無し][通常論文]
  • I. Yabe, H. Sasaki, K. Tashiro, T. Matsuura, T. Takegami, T. Satoh
    JOURNAL OF MEDICAL GENETICS 39 8 46  2002年08月 [査読無し][通常論文]
  • RP Grewal, M Achari, T Matsuura, A Durazo, E Tayag, L Zu, SM Pulst, T Ashizawa
    ARCHIVES OF NEUROLOGY 59 8 1285 - 1290 2002年08月 [査読無し][通常論文]
     
    Background: Spinocerebellar ataxia type 10, an autosomal dominant disease characterized by ataxia and seizures, is caused by a large expansion of an unstable ATTCT pentanucleotide repeat. Objectives: To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families. Design: Clinical characterization and genotype-phenotype correlation. Setting: Studies at 2 medical schools with private practice referral. Patients: Twenty-two affected individuals from 2 large Mexican American pedigrees. Results: Of the 22 individuals, ataxia was the initial symptom in 2 1; seizure disorders developed in 11, mostly within several years following the onset of ataxia. The seizure frequency was different in the 2 families: 3 (25%) of 12 had seizures in family 1, and 8 (80%) of 10 had seizures in family 2 (P=.01). A brain magnetic resonance imaging or computed tomographic scan showed cerebellar atrophy in all patients examined. An electroencephalogram demonstrated epileptiform discharges in 4 of 8 patients studied. Although anticipation was apparent in both families, only family I showed a strong inverse correlation between age of onset and repeat number (r(2)=0.79, P=.001). In family 1, 8 transmissions, of which 7 were paternal, resulted in an average gain of 1940 repeats. In contrast, despite anticipation, 2 affected male subjects transmitted their expanded alleles to 8 progenies, with an average loss of 755 repeats, in family 2. Conclusions: Seizure is an integral part of the spinocerebellar ataxia type 10 phenotype, with documented morbidity and mortality. Family-dependent factors may alter the frequency of the seizure phenotype and the pattern of intergenerational repeat size changes, making the genotype-phenotype correlation complex.
  • T Sato, S Arulmozhiraja, H Niino, S Sasaki, T Matsuura, A Yabe
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 124 16 4512 - 4521 2002年04月 [査読有り][通常論文]
     
    Toward direct observation of benzdiynes, we investigated the wavelength-selective photolyses of five kinds of benzenetetracarboxylic dianhydride derivatives in nitrogen matrixes at 13 K. In the first step of the photolyses, all dianhydrides were converted into benzynedicarboxylic anhydrides with loss of CO and CO2 upon irradiation at 308 nm. In the second step, the benzyne intermediates were photolyzed at 266 nm. In these photolyses, the generation of two kinds of benzdiynes, 3,6-difluoro-1,4-benzdiyne and 3,6-b is (trifluoromethyl)-1,4-benzdiyne, was confirmed by good correspondence between observed and calculated IR spectra. These benzdiynes were converted into the corresponding hexatriynes upon further irradiation at 266 nm. Benzdiynes were not observed in the photolyses of the other three dianhydrides: only hexatriynes were observed as major photoproducts. These results suggested that benzdiynes were generated first and then converted into hexatriynes and that the efficiency of the decomposition of benzdiynes depended on the substituents. The dynamics of the generation and decomposition of benzdiynes in the matrixes was analyzed by using a successive reaction scheme.
  • H Fujigasaki, S Tardieu, A Camuzat, G Stevanin, E LeGuern, T Matsuura, T Ashizawa, A Durr, A Brice
    ANNALS OF NEUROLOGY 51 3 408 - 408 2002年03月 [査読無し][通常論文]
  • T Matsuura, LPW Ranum, Volpini, V, M Pandolfo, H Sasaki, K Tashiro, K Watase, HY Zoghbi, T Ashizawa
    NEUROLOGY 58 6 983 - 984 2002年03月 [査読無し][通常論文]
  • T Matsuura, T Ashizawa
    ANNALS OF NEUROLOGY 51 2 271 - 272 2002年02月 [査読無し][通常論文]
  • T Matsuura, T Ashizawa
    TRIPLE REPEAT DISEASES OF THE NERVOUS SYSTEMS 516 79 - 97 2002年 [査読有り][通常論文]
  • A Rasmussen, T Matsuura, L Ruano, P Yescas, A Ochoa, T Ashizawa, E Alonso
    ANNALS OF NEUROLOGY 50 2 234 - 239 2001年08月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by expansion of an unstable ATTCT repeat. SCA10 has been described as a pure cerebellar syndrome accompanied by seizures and has been recognized only in families of Mexican origin. We describe clinical and molecular findings of 18 patients in four Mexican families with SCA10. Affected individuals had an average age at onset of 26.7 years (range 14-44 years) and ATTCT repeats ranging from 920 to 4,140 repeats. We could not detect significant anticipation or correlation between repeat size and age at onset, probably due to the small sample size. In addition to pure cerebellar ataxia and seizures, patients often showed soft pyramidal signs, ocular dyskinesia, cognitive impairment, and/or behavioral disturbances. Brain magnetic resonance imaging showed predominant cerebellar atrophy, and nerve conduction studies indicated polyneuropathy in 66% of patients. One family showed hepatic, cardiac, and hematological. abnormalities in affected members. These findings suggest that a wide range of tissues may be affected in SCA10, including those outside of the cerebellum and cerebral cortex.
  • EK Tan, S Nagamitsu, T Matsuura, M Khajavi, J Jankovic, W Ondo, T Ashizawa
    NEUROSCIENCE LETTERS 305 1 70 - 72 2001年06月 [査読無し][通常論文]
     
    a particular alcohol dehydrogenase (ADH) polymorphism (allele A1) in the promoter region of the gene has been recently demonstrated to be associated with increased risk of Parkinson's disease (PD). In a case control study, we examine frequencies of ADH A1 allele in 100 PD patients (i.e. 200 alleles), 100 diseased controls (i.e. 200 alleles), and 194 healthy controls (i.e. 388 alleles). In addition, we study possible association of a combined non-amyloid component of plaque (NACP-Rep 1) allele and ADH A1 allele with risk of PD. There was no statistical significance of the frequencies of BDH A1 allele between PD patients 12/200 (6%), diseased controls 13/200 (6.5%), and healthy controls 20/388 (5.2%). No strong evidence of an association was found between ADH A1 allele and PD susceptibility in our study patients, There was also no suggestion of linkage disequilibrium between NACP-Rep 1 and ADH A1 alleles. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
  • S Nagamitsu, T Matsuura, M Khajavi, R Armstrong, C Gooch, Y Harati, T Ashizawa
    Neurology 55 11 1697 - 1703 2000年12月 [査読無し][通常論文]
     
    Objectives: To identify the disease-causing mutation and its molecular consequence for a clinically distinct type of myotonic myopathy. Backgrounds: The authors encountered a unique myotonic disorder of early onset in a 37-year-old man and his 47-year-old sister. Methods: After examining known loci of inherited myotonic disorders, the authors looked for mutations within the CLCN1 gene using single strand conformation polymorphism and direct sequencing. To investigate the disease mechanism, reverse transcriptase PCR analyses of total RNA were performed. Results: In the proband and his affected sister, two novel mutations comprising a compound heterozygous state in the CLCN1 gene were identified: 1) a base (G) insertion in exon 7 generating a premature termination codon (fs289X) in the D5 domain, and 2) a C-to-T substitution in exon 23 resulting in a missense mutation (P932L). These mutations accompanied a clinical phenotype that is distinguishable from recessive myotonia congenita by progressive generalized muscle weakness, severe distal muscle atrophy, joint contractures, high serum creatine kinase levels, and conspicuous myopathic changes on muscle histopathology. Reverse transcriptase PCR analyses detected only the P932L mutant mRNA in skeletal muscle, suggesting that the fs289X mRNA is degraded rapidly. Conclusions: These data suggest that fs289X is a null mutation, rendering the patients with the compound heterozygous genotype of fs289X/P932L to exclusively express P932L homomeric channels that may have caused the "dystrophic" phenotype.
  • T Matsuura, T Yamagata, DL Burgess', A Rasmussen, RP Grewal, K Watase, M Khajavi, AE McCall, CF Davis, L Zu, M Achari, SM Pulst, E Alonso, JL Noebels, DL Nelson, HY Zoghbi, T Ashizawa
    NATURE GENETICS 26 2 191 - 194 2000年10月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1.2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1.2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r(2)=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.
  • KJ Swoboda, BW Soong, C McKenna, ERP Brunt, M Litt, JF Bale, T Ashizawa, LB Bennett, AM Bowcock, ES Roach, D Gerson, T Matsuura, PT Heydemann, MP Nespeca, J Jankovic, M Leppert, LJ Ptacek
    NEUROLOGY 55 2 224 - 230 2000年07月 [査読無し][通常論文]
     
    Objective: To clinically characterize affected individuals in families with paroxysmal kinesigenic dyskinesia (PKD), examine the association with infantile convulsions, and confirm linkage to a pericentromeric chromosome 16 locus. Background PKD is characterized by frequent, recurrent attacks of involuntary movement or posturing in response to sudden movement, stress, or excitement. Recently, an autosomal dominant PKD locus on chromosome 16 was identified. Methods: The authors studied 11 previously unreported families of diverse ethnic background with PKD with or without infantile convulsions and performed linkage analysis with markers spanning the chromosome 16 locus. Detailed clinical questionnaires and interviews were conducted with affected and unaffected family members. Results: Clinical characterization and sampling of 95 individuals in 11 families revealed 44 individuals with paroxysmal dyskinesia, infantile convulsions, or both. Infantile convulsions were surprisingly common, occurring in 9 of 11 families. In only two individuals did generalized seizures occur in later childhood or adulthood. The authors defined a 26-cM region using linkage data in 11 families (maximum lod score 6.63 at empty set = 0). Affected individuals in one family showed no evidence for a shared haplotype in this region, implying locus heterogeneity. Conclusions: Identification and characterization of the PKD/infantile convulsions gene will provide new insight into the pathophysiology of this disorder, which spans the phenotypic spectrum between epilepsy and movement disorder.
  • EK Tan, T Matsuura, S Nagamitsu, M Khajavi, J Jankovic, T Ashizawa
    Neurology 54 5 1195 - 1198 2000年03月 [査読無し][通常論文]
     
    An allele (263bp) of the nonamyloid component of plaques (NACP)-Rep1 polymorphism has shown association with sporadic PD in a German population. The authors studied this polymorphism in 100 American PD patients and 100 healthy controls. The authors also studied 46 essential tremor (ET) and 55 Huntington's disease (HD) patients. Allele 263bp was significantly higher in PD patients (OR = 3.86) and ET patients (OR = 6.42) but not HD patients, compared with healthy controls. The association of allele 263bp with PD and ET suggests a possible etiologic link between these two conditions.
  • DL Burgess, T Matsuura, T Ashizawa, JL Noebels
    EPILEPSIA 41 1 24 - 27 2000年01月 [査読無し][通常論文]
     
    Purpose: Voltage-dependent calcium channel mutations have been associated with spinocerebellar ataxia in humans (SCA6) and with ataxia, progressive cerebellar degeneration, and epilepsy in mice (tottering, lethargic, and stargazer). A novel autosomal dominant spinocerebellar ataxia syndrome with epilepsy (SCA10) was recently mapped to chromosome 22q13. The human ortholog of the mouse stargazer locus, the calcium channel gamma subunit gene CA CNG2, also is located in this region. Because the phenotypes of stargazer mice and SCA10 patients were similar, consisting of both cerebellar ataxia and seizures, we hypothesized that CACNG2 was a likely candidate for the SCA10 locus. Methods: Polymerase chain reaction (PCR) based assays were developed for two polymorphic microsatellite markers near CACNG2. The location of CACNG2 was determined by linkage and haplotype analysis of the genotypes of 22 individuals from a human pedigree segregating SCA10. Results: SCA10 was previously localized distal to marker D22S1177 on chromosome 22q13. We determined that CACNG2 was linked to D22S283 and D22S1177 with the marker order: centromere-D22S283-bcmDLB1 (CACNG2)-D22S1177-D22S423-telomere. Thus CA CNG2 is located proximal to the SCA10 recombinant interval. Conclusions: Here we report the first genetic linkage of CACNG2 on chromosome 22q13 and exclude it as a candidate for SCA10. In addition, our data clarify the relation between the physical and genetic linkage maps of this region and will facilitate isolation of the SCA10 gene.
  • T Matsuura, H Sasaki, Yabe, I, K Hamada, T Hamada, M Shitara, K Tashiro
    JOURNAL OF NEUROLOGY 246 9 835 - 839 1999年09月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of unstable CAG repeats within the coding region of the novel gene, ataxin-2, on chromosome 12q24.1. We analyzed CAG repeat size of the SCA2 allele in two deceased patients (father and daughter) to investigate the repeat mosaicism in CNS regions. The CAG repeat size was examined using lymphoblastoid cell lines, frozen brain tissues, and paraffin-embedded tissues. In each patient the major repeat size of the expanded allele varied within the brain or spinal cord (father, 39-42; daughter, 39-47 repeats), and was smaller by three to eight repeats in the cerebellum than in other CNS regions. Our results are in agreement with the findings in other polyglutamine disorders showing somatic mosaicism.
  • T Matsuura, M Achari, M Khajavi, LL Bachinski, HY Zoghbi, T Ashizawa
    ANNALS OF NEUROLOGY 45 3 407 - 411 1999年03月 [査読無し][通常論文]
     
    We investigated a family with a new type of autosomal dominant cerebellar ataxia (ADCA) in which pure cerebellar ataxia is often accompanied with epilepsy. No CAG repeat expansions were detected at the spinocerebellar ataxia (SCA) type 1, 2, 3, 6, or 7 locus, and SCAs 4 and 5 were excluded by linkage analysis. We found linkage between the disease locus and D22S274 (Zmax = 3.86 at theta = 0.00) and two other makers in 22q13-qter. Haplotype analysis of the crossover events and the multipoint linkage mapping localized the disease locus to an 8.8-cM region between D22S1177 and D22S1160.
  • A Ogata, K Nagashima, K Yasui, T Matsuura, K Tashiro
    JOURNAL OF THE NEUROLOGICAL SCIENCES 159 2 135 - 139 1998年08月 [査読無し][通常論文]
     
    Thyrotropin-releasing hormone (TRH) has been reported to have some possibilities toward the treatment of affective CNS disorders. However, long term treatments with daily injections are often required. Effects of TRH-SR (sustained release microspheres of TRH) which is encapsulated in copoly (dl-lactic/glycolic acid) using an in-water drying method were investigated in experimental Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test and high performance liquid chromatography (HPLC) with an electrochemical detector (ECD). We have already reported that in adult Fischer rats killed 12 weeks after infection with JEV at the age of 13 days a marked decrease of tyrosine hydroxylase-positive neurons was found in the bilateral substantia nigra. TRH SR (3 mg/kg per 2 weeks, 4 times injections, subcutaneous [SC]) improved bradykinesia observed in the JEV-induced parkinsonism rats. Dopamine (DA) concentrations in the JEV-infected rats were profoundly reduced in the striatum as compared with controls. TRH-SR (3 mg/kg, once, SC) increased DA in the striatum 7 days after the injection. Although the pathomechanism of post-encephalitic parkinsonism is different from that of Parkinson's disease and TRH possesses a variety of CNS effects as well, these results suggest that TRH SR play a possible role in the treatment of Parkinson's disease in addition to post-encephalitic parkinsonism as a supportive drug of L-DOPA. (C) 1998 Elsevier Science B.V. All rights reserved.
  • Yabe, I, H Sasaki, T Matsuura, A Takada, A Wakisaka, Y Suzuki, T Fukazawa, T Hamada, T Oda, A Ohnishi, K Tashiro
    JOURNAL OF THE NEUROLOGICAL SCIENCES 156 1 89 - 95 1998年03月 [査読無し][通常論文]
     
    Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in the gene encoding the alpha(1A)-voltage-dependent-calcium channel subunit (CACNL1A4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prevalence of SCAB in the Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA m. The specificity and stability of the CAG repeat were examined in additional individuals and families with other miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12 proband cases with ADCA III, but not in others. The CAG repeat was 21-33 in the disease-associated alleles (n = 56), and 4-18 in normal alleles (n = 1148). Expanded alleles were stable during transmission, and a significant inverse correlation for CAG repeat number with age at onset was noted. Our results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified. (C) 1998 Elsevier Science B.V.
  • T Matsuura, H Sasaki, K Tashiro
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 64 2 161 - 161 1998年02月 [査読無し][通常論文]
  • T Matsuura, H Sasaki, A Wakisaka, T Hamada, F Moriwaka, K Tashiro
    JOURNAL OF THE NEUROLOGICAL SCIENCES 151 1 65 - 70 1997年10月 [査読無し][通常論文]
     
    Autosomal dominant spastic paraplegia (ADSP) is a genetically heterogenous disorder. To date, 3 loci of ADSP have been identified on chromosome 2p, 14q, and 15q, but specific gene mutations remain unknown. To determine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 individuals clinically examined, 15 were affected. The main feature in the affected individuals was a slowly progressive spastic paraplegia, associated with upper limb hyperreflexia (58%), reduction of vibration sense (27%) and bladder disturbance (13%). Age at onset ranged from 13 to 50 years with a mean of 30.3+/-14.2 (SD). There were 6 parent-child pairs with anticipation and at least 3 others with 'anti-anticipation'. Linkage with 14q and 15q ADSP loci was excluded, and a highly significant lod score was obtained only in the case of the 2p locus (Z(max) = 3.53 for D2S300/D2S352, at theta=0.00). Our study is the first to confirm the existence of 2p-linked ADSP in the Japanese. There is a significant variety in age at onset and disease severity in these 2p-linked families, but the implication for underlying ADSP mutation is not clear. (C) 1997 Elsevier Science B.V.
  • M Nakamura, S Mita, T Matuura, K Nagashima, H Tanaka, M Ando, M Uchino
    JOURNAL OF THE NEUROLOGICAL SCIENCES 150 2 161 - 165 1997年09月 [査読無し][通常論文]
     
    We examined the expression level of androgen receptor (AR) messenger RNA (mRNA) in the motoneurons from patients with X-linked spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) using in situ hybridization. Although AR mRNA was detected in motoneurons from the SBMA patient, the expression level was lower than that from the patients with ALS, despite similar loss of motoneurons. The expression level of AR mRNA in the dorsal nucleus of Clarke from the patient with SBMA was similar to that in the patients with ALS, suggesting that the qualities of the mRNA were similar in each spinal cord sample and that AR mRNA was uniquely reduced in the motoneurons of the SBMA patient. Decreased levels of AR mRNA map be involved in the pathogenesis of SBMA resulting in degeneration of motoneurons. (C) 1997 Elsevier Science B.V.
  • 伴性劣性球脊髄性筋萎縮症におけるアンドロゲン受容体発現と神経病変選択性の研究.
    北海道医学雑誌 71 785 - 789 1996年 [査読無し][通常論文]
  • H SASAKI, A WAKISAKA, T FUKAZAWA, K IWABUCHI, T HAMADA, A TAKADA, E MUKAI, T MATSUURA, T YOSHIKI, K TASHIRO
    JOURNAL OF THE NEUROLOGICAL SCIENCES 133 1-2 128 - 133 1995年11月 [査読無し][通常論文]
     
    Machado-Joseph disease (MJD) is caused by abnormal expansion of an unstable CAG repeat in a novel gene locating on chromosome 14q32.1. We analysed this CAG repeat polymorphism with 66 Japanese MJD patients, All the patients were selectively associated with abnormal expansion of the CAG repeat. Repeat length of the mutant allele did not overlap that of normal allele and closely correlated with not only age at onset but also with clinical phenotypes. CAG repeat size is apparently related to a wide variety of phenotypic presentations in MJD.
  • A OGATA, T MATSUURA, K TASHIRO, F MORIWAKA, T DEMURA, T KOYANAGI, K NAGASHIMA
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 57 10 1274 - 1275 1994年10月 [査読無し][通常論文]
  • T IHARA, H SASAKI, A WAKISAKA, A TAKADA, T YOSHIKI, T MATSUURA, T HAMADA, Y SUZUKI, K TASHIRO
    JAPANESE JOURNAL OF HUMAN GENETICS 39 3 305 - 313 1994年09月 [査読有り][通常論文]
     
    We did a linkage study of 2 multigenerational pedigrees with dominant olivopontocerebellar atrophy (OPCA) other than SCA1, with chromosome 12q microsatellites. Multipoint linkage analysis led to the conclusion that the disease locus locates within the 6.2 cM interval between IGF1 and D12S84/D12S105. This result coincides with that of Cuban ataxia pedigrees designated as SCA2. Our study provides genetic evidence that dominant OPCA in the Japanese consists of at least two genetically different disorders; SCA1 and SCA2.
  • T SATO, R DENNO, Y YUYAMA, T MATSUURA, Y KANISAWA, K HIRATA
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 24 4 360 - 362 1994年 [査読無し][通常論文]
     
    We present herein the case of a woman who developed unexpected complications following a laparoscopic cholecystectomy. The clinical manifestations were unique in that symptoms of obstructive jaundice were in fact caused by endo-clips which had migrated into the common bile duct, and the resulting choledochoduodenal fistula presented as persistant cholangitis. While the overall safety of this new procedure appears to be superior to that of open cholecystectomy, the risk of bile duct injury seems more likely. This case stresses the need for caution by surgeons, and emphasizes the necessity for careful surveillance and strict follow-up to ensure the safety of this procedure.
  • K YOSHIDA, F MORIWAKA, T MATSUURA, T HAMADA, K TASHIRO
    JAPANESE JOURNAL OF PSYCHIATRY AND NEUROLOGY 47 3 621 - 625 1993年09月 [査読有り][通常論文]
     
    A 68-year-old woman with parkinsonism showed cortical myoclonus and seizures under antiparkinsonian medication. Myoclonus was induced and enhanced by L-dopa, developing into generalized seizures. EEG was abnormal and somatosensory-evoked potentials (SEPs) showed giant SEPs, transcortical reflex (C reflex) and jerk locked potentials. Myoclonus and seizures disappeared after discontinuation of L-dopa and the introduction of valproate sodium (VPA). We described the occurrence of L-dopa-induced myoclonus and seizures in a case of parkinsonism with its SEPs findings,
  • T MATSUURA, A OGATA, T DEMURA, F MORIWAKA, K TASHIRO, T KOYANAGI, K NAGASHIMA
    NEUROSCIENCE LETTERS 158 1 5 - 8 1993年08月 [査読無し][通常論文]
     
    Androgens play an important role in motoneuron growth, development and regeneration. We proved the existence of androgen receptor (AR) in the motoneurons of the rat spinal cord by the immunohistochemical stain and Western blotting. The possibility that AR protein in spinal cord is expressed in tissue-specific form is proposed, being different from other androgen-dependent tissues. AR abnormality in X-linked spinal and bulbar muscular atrophy (SBMA) among a variety of motor neuron diseases were reported recently. Our study may give some clue to the AR abnormality leading to the degeneration of motoneurons.
  • T MATSUURA, Y SHIMIZU, H FUJIMOTO, T MIYAZAKI, S KANO
    LANCET 340 8834-5 1553 - 1553 1992年12月 [査読無し][通常論文]
  • T MATSUURA, T DEMURA, Y AIMOTO, T MIZUNO, F MORIWAKA, K TASHIRO
    NEUROLOGY 42 9 1724 - 1726 1992年09月 [査読無し][通常論文]
     
    X-linked spinal and bulbar muscular atrophy (SBMA) is usually associated with feminization and hypogonadism. We were unable to find androgen receptor (AR) in the scrotal skin of three patients with SBMA, and propose that AR abnormality is the cause of the disease.
  • T MATSUURA, Y KANISAWA, T SATO, T SAITO, K HIRATA
    Lancet 340 8814 306 - 306 1992年08月 [査読無し][通常論文]
  • Kennedy-Alter-Sung 症候群における骨格筋障害分布様式について-筋CTと筋力評価による比較検討.
    神経内科 37 1 - 6 1992年 [査読無し][通常論文]
  • T. Matsuura, Y. Aimoto, F. Moriwaka, K. Tashiro, K. Nonomura
    Clinical Neurology 31 3 291 - 295 1991年 [査読無し][通常論文]
  • 松本 博之, 長内 忍, 小野寺 壮吉, 秋葉 裕二, 中野 均, 大松 広伸, 松浦 修, 飛世 克之, 坂井 英一
    日本胸部疾患学会雑誌 28 7 961 - 970 1990年 [査読無し][通常論文]
  • Hidenao Sasaki, Akemi Wakisaka, Toshiaki Katoh, Michihiro C. Yoshida, Takeshi Hamada, Kohji Shima, Tohru Matsuura, Kunio Tashiro
    The Japanese Journal of Human Genetics 33 4 423 - 438 1988年12月 [査読有り][通常論文]
     
    Both autosomal dominant olivo-ponto-cerebellar atrophy (OPCA) and Holmes' ataxia are the progressive neurodegenerative disorders of adulthood with unknown biochemical defects. In order to determine the genetic locus and possible genetic heterogeneity, linkage study was performed in 19 OPCA families comprising 180 individuals with 60 affected patients, and two Holmes' ataxia families comprising 39 individuals with 10 affected patients. By using computer program LIPED, linkage of each disorder was analyzed to 12 blood groups, 5 red cell enzymes, HLA-A, -B, -C, and F13A. No evidence suggesting linkage to these two disorders was obtained in the markers examined, including three 6p markers such as HLA, GLO1, and F13A. Furthermore, in 14 out of 15 HLA-informative OPCA families, negative lod scores for OPCA with HLA were obtained at most recombination fractions. Our results provide further evidence suggesting the genetic heterogeneity of dominant OPCA. © 1988 The Japan Society of Human Genetics.
  • H SASAKI, A WAKISAKA, T KATOH, MC YOSHIDA, T HAMADA, K SHIMA, T MATSUURA, K TASHIRO
    JAPANESE JOURNAL OF HUMAN GENETICS 33 4 423 - 438 1988年12月 [査読有り][通常論文]
  • F. Moriwaka, K. Tashiro, T. Matsuura, S. Satoh, S. Doi, T. Kuramae
    Brain and Nerve 39 4 375 - 379 1987年 [査読有り][通常論文]
  • T. Matsuura, T. Chiba, K. Yamada, K. Shima, K. Tashiro
    Clinical Neurology 22 4 336 - 342 1982年 [査読有り][通常論文]
     
    Slow eye movements are reported in some neurological diseases, such as spinocerebellar degeneration, Huntington's chorea, progressive supranuclear palsy, Wilson's disease and so on. Most of the reported cases show horizontal slow eye movements predominantly, however vertical slow eye movements are extremely rare. This 25-year-old woman gradually developed unsteady gait, swallowing difficulty, slurred speech and learning disability since 14 years old. Neurologic examination showed cerebellar ataxia, dementia, hyperreflexia in lower extremities and occasional choreo-athetotic movements of hands. Furthermore, the most striking feature was vertical slow eye movements, though horizontal eye movement was normal. Electro-oculogram confirmed markedly slow pursuit eye movement, i.e. 0.06 Hz, in vertical direction. Liver-spleen scintigram showed mild splenomegaly, and sea-blue histiocytes were observed in bone marrow. Two cell types were recognized in sea-blue histiocytes, in which the cytoplasm of one type was filled with dense blue granules and the other with scattered granules. Simple foamy cells were also observed. Rectal biopsy revealed degenerative change in ganglion cells of Meissner and Auerbach. Sphingomyelinase activity of cultured skin-fibroblasts showed 56% of control levels. This finding suggests that the case is a variant of Niemann-Pick disease.

書籍

  • Spinocerebellar Ataxia Type 10 2002 Apr 23 [Updated 2019 Sep 19].
    松浦 徹 (担当:共著)
    In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1175/ 2019年09月
  • 「筋ジストロフィーの病型診断を進めるための手引き」(肢帯型・先天性・筋強直性ジストロフィーを念頭に)
    松浦 徹 (担当:分担執筆範囲:第3章 筋強直性ジストロフィー(1型が否定された場合の病型診断を念頭に))
    厚生労働科学研究費 難治性疾患政策研究事業 「筋ジストロフィーの標準的医療普及のための調査研究」班 編 2019年04月
  • Myotonic Dystrophy: Disease Mechanism, Current Management and Therapeutic Development
    松浦 徹 (担当:分担執筆範囲:Genetics of Myotonic Dystrophy)
    Springer 2018年10月
  • 非翻訳領域リピート病のRNA病態.
    ()
    Medical Science Digest 2006年
  • SCA10の分子遺伝学.
    ()
    神経研究の進歩 2006年
  • 非翻訳領域リピート病のRNA病態.
    ()
    Medical Science Digest 2006年
  • SCA10の分子遺伝学.
    ()
    神経研究の進歩 2006年
  • Spinocerebellar ataxia type 10: a disease caused by a large ATTCT repeat expansion.
    ()
    Adv Exp Med Biol 2002年
  • Spinocerebellar Ataxia Type 10: A Disease Caused by a Large ATTCT Repeat Expansion. In: Trinucleotide Expansions and Human Diseases.
    ()
    Timchenko L ed. Landes Bioscience, Georgetown 2002年
  • Spinocerebellar ataxia type 10: a disease caused by a large ATTCT repeat expansion.
    ()
    Adv Exp Med Biol 2002年
  • Spinocerebellar Ataxia Type 10: A Disease Caused by a Large ATTCT Repeat Expansion. In: Trinucleotide Expansions and Human Diseases.
    ()
    Timchenko L ed. Landes Bioscience, Georgetown 2002年
  • Spinocerebellar ataxia type 10. In: Genetics of Movement Disorders.
    ()
    Pulst SM ed. Academic Press, San Diego 2001年
  • SCA10遺伝子の同定―新しいリピート (pentanucleotide repeat) 病.
    ()
    臨床神経学 2001年
  • Spinocerebellar ataxia type 10. In: Genetics of Movement Disorders.
    ()
    Pulst SM ed. Academic Press, San Diego 2001年
  • SCA10遺伝子の同定―新しいリピート (pentanucleotide repeat) 病.
    ()
    臨床神経学 2001年
  • A glycoprotein detected with peanut agglutin: a specific marker of myelin and human lymphocyte lines. In: Japan intractable diseases research foundation publication No.26 Neuroimmunological diseases, recent in pathogenesis and treatment
    ()
    Igata A ed., University of Tokyo Press, Tokyo 1989年
  • A glycoprotein detected with peanut agglutin: a specific marker of myelin and human lymphocyte lines. In: Japan intractable diseases research foundation publication No.26 Neuroimmunological diseases, recent in pathogenesis and treatment
    ()
    Igata A ed., University of Tokyo Press, Tokyo 1989年

講演・口頭発表等

  • Pancreatic Cancer in FXTAS Individual: Altered DNA Damage Response?  [通常講演]
    松浦 徹
    9th International Conference on Unstable Microsatellites & Human Disease 2018年04月 口頭発表(一般)
  • オーバービュー:リピート病の病態と不安定性メカニズム  [通常講演]
    松浦 徹
    2017年度生命科学系学会合同年次大会(ConBio2017) 2017年12月 シンポジウム・ワークショップパネル(指名)
  • RNA disease mechanism in DM1 and SCA10 brain  [招待講演]
    松浦 徹
    第38回日本神経科学大会 2015年07月 シンポジウム・ワークショップパネル(指名)
  • 筋強直性ジストロフィーの分子病態~治療  [通常講演]
    松浦 徹
    第6回遺伝カウンセリングアドバンスドセミナー 2015年01月 公開講演,セミナー,チュートリアル,講習,講義等
  • Parkinsonism in SCAs  [招待講演]
    松浦 徹
    13th International Parkinson’s Disease Symposium in Takamatsu (iPDST) 2014年02月 口頭発表(招待・特別)
  • よくわかる“遺伝”  [招待講演]
    松浦 徹
    第54回日本神経学会学術大会 2013年05月 シンポジウム・ワークショップパネル(指名)
  • RNA-mediated disease mechanism of spinocerebellar ataxia type 10  [通常講演]
    松浦 徹
    7th International Conference on Unstable Microsatellites & Human Disease 2012年06月 口頭発表(一般)
  • RNA-mediated disease mechanism of spinocerebellar ataxia type 10  [招待講演]
    松浦 徹
    第51回日本神経学会学術大会 2010年05月 シンポジウム・ワークショップパネル(指名)
  • 脊髄小脳失調症10型と筋強直性ジストロフィーのRNA神経病態  [招待講演]
    松浦 徹
    第1回生体制御科学シンポジウム・第36回岡山脳研究セミナー 2010年03月 シンポジウム・ワークショップパネル(指名)
  • Misregulation of diacylglycerol kinase eta (DGKη) splicing as a potential cause of neuropsychiatric symptoms in myotonic dystrophy type 1  [通常講演]
    松浦 徹
    7th International Myotonic Dystrophy Consortium Meeting 2009年09月 口頭発表(一般)
  • 脊髄小脳失調症10型の分子遺伝学的解析  [招待講演]
    松浦 徹
    藤田保健衛生大学総合医科学研究所セミナー 2008年06月 口頭発表(招待・特別)
  • 脊髄小脳失調症10型の分子遺伝学的解析  [招待講演]
    松浦 徹
    第49回日本神経学会総会 2008年05月 シンポジウム・ワークショップパネル(指名)
  • Myotonic dystrophy type 2 in Japan: distinct ancestral origin from Caucasian families  [通常講演]
    松浦 徹
    6th international Myotonic Dystrophy Consortium Meeting 2007年09月 口頭発表(一般)
  • SCA10 Update  [招待講演]
    松浦 徹
    2005 Annual Membership Meeting of National Ataxia Foundation 2005年03月 公開講演,セミナー,チュートリアル,講習,講義等
  • “SCA10遺伝子の同定―新しいリピート (pentanucleotide repeat) 病”  [招待講演]
    芦澤哲夫, 松浦 徹
    第42回日本神経学会総会 2001年05月 シンポジウム・ワークショップパネル(指名)
  • Large expansion of ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10  [招待講演]
    松浦 徹
    125th Annual Meeting of the American Neurological Association 2000年10月 口頭発表(招待・特別)
  • Large expansion of ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10  [通常講演]
    松浦 徹
    50th Annual Meeting of the American Society of Human Genetics 2000年10月 口頭発表(招待・特別)

作品等

  • 平成19年度財団法人那古野医学振興会 研究奨励金 (40万円) 「筋強直性ジストロフィー2型のゲノム解析」
    2008年 -2008年
  • 平成18年度財団法人日本脳神経外科 学術研究助成 (50万円) 「非翻訳リピート病のスプライシング異常と治療の試み」
    2007年 -2007年
  • 平成18年度財団法人那古野医学振興会 研究奨励金 (60万円) 「筋強直性ジストロフィー2型の分子遺伝学的解析」
    2007年 -2007年
  • 厚生労働科学研究費補助金「難治性疾患克服研究事業」 (研究分担者) 「運動失調症に関する調査研究(西澤正豊)」130万円(H18)、110万円 (H19)
    2006年 -2007年
  • 名古屋大学医学部 平成19年度八木基金 海外研究交流助成(15万円)
    2007年
  • 2006年度財団法人武田科学振興財団医学系研究奨励金 (200万円) 「SCA10非翻訳領域リピート伸長変異の神経変性メカニズムの解明」
    2006年 -2006年
  • 第14回(平成18年度)財団法人市原国際奨学財団 研究助成 (50万円) 「脊髄小脳変性症10型非翻訳領域ATTCTリピート伸長変異の神経変性病態機構の解明」
    2006年 -2006年
  • 第24回(平成18年度)公益信託日本医学会総会記念医学振興基金 (100万円) 「脊髄小脳変性症10型非翻訳領域ATTCTリピート伸長変異の神経変性病態機構の解明」
    2006年 -2006年
  • 第20回(平成18年度)公益信託加藤記念難病研究助成基金(200万円) 「非翻訳領域リピート病の異常スプライシング修正の試み」
    2006年 -2006年
  • 第23回(平成18年度)日東学術振興財団(70万円) 「脊髄小脳変性症10型非翻訳領域ATTCTリピート伸長変異の神経変性病態機構の解明」
    2006年 -2006年
  • 第18年度(第1回)名古屋大学学術振興基金 (25万円) 「自然発症筋萎縮モデルラットAftm1の病態分子機構の解明」
    2006年 -2006年
  • 第23回(平成17年度) 財団法人三共生命科学研究振興財団研究助成 (200万円) 「筋緊張性ジストロフィーにおけるスプライシング異常補正薬スクリーニング」
    2005年 -2006年
  • Research Grants (Olivopontocerebellar atrophy and related disorders) from NORD ($40,000) “Characterization of the SCA10 ATTCT Expansion and Implications of the Sequence Configurations”
    2005年 -2005年
  • Research Grants from National Ataxia Foundation, MN, USA ($25,000) “The role of interruptions in SCA10 expansion and disease”
    2005年 -2005年
  • Research Grants (Olivopontocerebellar atrophy and related disorders) from NORD ($40,000) “Characterization of the SCA10 ATTCT Expansion and Implications of the Sequence Configurations”
    2005年 -2005年
  • Research Grants from National Ataxia Foundation, MN, USA ($25,000) “The role of interruptions in SCA10 expansion and disease”
    2005年 -2005年
  • Research Grants (Olivopontocerebellar atrophy and related disorders) from National Organization for Rare Disorders (NORD), CT, USA ($40,000) “Complete survey of SCA10 mutation in multiethnic ataxia patients”
    2003年 -2004年
  • Young Investigator Award from National Ataxia Foundation, MN, USA ($100,000) “RNA disease mechanism in spinocerebellar ataxia type 10”
    2003年 -2004年
  • Research Grants (Olivopontocerebellar atrophy and related disorders) from National Organization for Rare Disorders (NORD), CT, USA ($40,000) “Complete survey of SCA10 mutation in multiethnic ataxia patients”
    2003年 -2004年
  • Young Investigator Award from National Ataxia Foundation, MN, USA ($100,000) “RNA disease mechanism in spinocerebellar ataxia type 10”
    2003年 -2004年
  • Research Grants from National Ataxia Foundation, MN, USA ($30,000) “Search for an expansion mutation of ATTCT/AGAAT repeats in unassigned ataxia patients”
    2002年 -2002年
  • 第17回財団法人ブレインサイアンス振興財団 研究助成金 「Spinocerebellar ataxia type 10における病態機構の解析」
    2002年 -2002年
  • 第17回財団法人金原一郎記念医学医療振興財団基礎医学医療研究助成金「Spinocerebellar ataxia type 10 (SCA10) における変異RNA神経変性メカニズム」
    2002年 -2002年
  • Research Grants from National Ataxia Foundation, MN, USA ($30,000) “Search for an expansion mutation of ATTCT/AGAAT repeats in unassigned ataxia patients”
    2002年 -2002年
  • Research Grants from National Ataxia Foundation, MN, USA ($10,000) “Instability of the expanded SCA10 ATTCT pentanucleotide repeat ”
    2001年 -2001年
  • Research Grants from National Ataxia Foundation, MN, USA ($10,000) “Instability of the expanded SCA10 ATTCT pentanucleotide repeat ”
    2001年 -2001年

MISC

  • Isolated hand palsyを呈した脳梗塞 機能的MRIによる機能局在解析の検討
    古谷 浩平, 小澤 忠嗣, 大貫 良幸, 金 蓮姫, 横瀬 美里, 鈴木 雅之, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 松浦 徹, 川合 謙介, 藤本 茂 臨床神経学 58 (Suppl.) S279 -S279 2018年12月 [査読無し][通常論文]
  • 急性の精神症状を呈した症例における抗NMDA受容体抗体陽性率についての多施設共同研究
    安藤 喜仁, 嶋崎 晴雄, 塩田 勝利, 中尾 紘一, 島田 達洋, 倉田 和美, 黒田 仁一, 山下 晃弘, 佐藤 勇人, 佐藤 守, 衛藤 進吉, 大西 康則, 小林 勝司, 田中 惠子, 加藤 敏, 松浦 徹 臨床神経学 54 (Suppl.) S58 -S58 2014年12月 [査読無し][通常論文]
  • 滑川道人, 本多純子, 直井為任, 嶋崎晴雄, 松浦徹 日本神経学会学術大会プログラム・抄録集 55th 572 2014年 [査読無し][通常論文]
  • 林夢夏, 滑川道人, 角田顕子, 益子貴史, 小野さやか, 中尾紘一, 安藤喜仁, 澤田幹雄, 嶋崎晴雄, 松浦徹 日本神経学会学術大会プログラム・抄録集 55th 645 2014年 [査読無し][通常論文]
  • 世界初のプリオン蛋白遺伝子変異により発症した感覚自律神経性ニューロパチーの症例
    松薗 構佑, 池田 佳生, 佐藤 恒太, 香西 由子, 出口 章子, 倉田 智子, 森本 展年, 山下 徹, 出口 健太郎, 松浦 徹, 阿部 康二 臨床神経学 53 (5) 392 -392 2013年05月 [査読無し][通常論文]
  • SIADHを呈した抗アクアポリン4抗体関連脳症の1例
    出口 章子, 池田 佳生, 香西 由子, 松薗 構佑, 池田 雅美, 出口 健太郎, 森本 展年, 倉田 智子, 松浦 徹, 阿部 康二, 高橋 利幸 臨床神経学 53 (1) 69 -69 2013年01月 [査読無し][通常論文]
  • 岡山大学神経内科におけるSCD/MSA症例313例の検討
    池田 佳生, 大野 凌, 森本 展年, 倉田 智子, 出口 健太郎, 松浦 徹, 阿部 康二 臨床神経学 53 (1) 72 -72 2013年01月 [査読無し][通常論文]
  • α-synucleinopathyおよびtauopathyにおける脳MRI画像の検討
    武久 康, 倉田 智子, 森本 展年, 池田 佳生, 松浦 徹, 阿部 康二 臨床神経学 52 (12) 1510 -1510 2012年12月 [査読無し][通常論文]
  • 新しいALS/SCA crossroad mutation Asidan(SCA36)の嚥下障害
    森本 展年, 佐藤 恒太, 宮崎 一徳, 池田 佳生, 松浦 徹, 阿部 康二 臨床神経学 52 (12) 1517 -1517 2012年12月 [査読無し][通常論文]
  • 新しいALS/SCA crossroad mutation AsidanのRNA病態メカニズム
    松浦 徹, 明地 雄司, 池田 佳生, 森本 展年, 宮崎 一徳, 小林 果, 小泉 昭夫, 阿部 康二 臨床神経学 52 (12) 1400 -1400 2012年12月 [査読無し][通常論文]
  • 髄液抗GluRε2及び抗GluRδ2抗体陽性脳炎の1例
    松薗 構佑, 池田 佳生, 香西 由子, 出口 章子, 倉田 智子, 森本 展年, 出口 健太郎, 松浦 徹, 阿部 康二 臨床神経学 52 (6) 446 -446 2012年06月 [査読無し][通常論文]
  • 原発性胆汁性肝硬変に合併した多発筋炎の一例
    香西 由子, 池田 佳生, 出口 章子, 松薗 構佑, 出口 健太郎, 松浦 徹, 阿部 康二, 若林 宏, 池田 房雄 臨床神経学 52 (6) 450 -450 2012年06月 [査読無し][通常論文]
  • 高CK血症を合併した視神経脊髄炎(NMO)の2例
    出口 章子, 出口 健太郎, 松薗 構佑, 香西 由子, 河野 祥一郎, 森本 展年, 池田 雅美, 池田 佳生, 松浦 徹, 阿部 康二, 高橋 利幸 臨床神経学 52 (6) 448 -448 2012年06月 [査読無し][通常論文]
  • 岡山大学神経内科における特発性慢性肥厚性硬膜炎7例の検討
    香西 由子, 池田 佳生, 出口 章子, 松薗 構佑, 森本 展年, 高宮 資宜, 出口 健太郎, 山下 徹, 佐藤 恒太, 奈良井 恒, 真邊 泰宏, 松浦 徹, 阿部 康二 臨床神経学 52 (5) 383 -383 2012年05月 [査読無し][通常論文]
  • 掌蹠膿疱症に合併した両側遠位の上肢筋力低下の1例
    松薗 構佑, 河野 祥一郎, 香西 由子, 森本 展年, 出口 章子, 出口 健太郎, 池田 佳生, 松浦 徹, 阿部 康二 臨床神経学 52 (5) 386 -386 2012年05月 [査読無し][通常論文]
  • NOP56遺伝子イントロンにおける6塩基リピート拡張は脊髄小脳変性症36型を引き起こす
    小林 果, 阿部 康二, 松浦 徹, 池田 佳生, 人見 敏明, 土生 敏行, 劉 万洋, 奥田 裕子, 原田 浩二, 小泉 昭夫 日本衛生学雑誌 67 (2) 281 -281 2012年02月 [査読無し][通常論文]
  • Ning Liu, Kentaro Deguchi, Jingwei Shang, Xuemei Zhang, Fengfeng Tian, Toru Yamashita, Yasuyuki Ohta, Yoshio Ikeda, Tohru Matsuura, Koji Abe CEREBROVASCULAR DISEASES 34 122 -122 2012年 [査読無し][通常論文]
  • 「ALS様運動神経障害を伴う新規脊髄小脳変性症(SCA36) の原因遺伝子発見」
    小林果, 阿部康二, 松浦徹, 池田佳生, 人見敏明, 明地雄司, 土生敏行, 劉万洋, 奥田裕子, 小泉昭夫 第11回 分子予防環境医学 研究会 2012年1月 岡山 2012年 [査読有り][通常論文]
  • ALSモデルマウスの脊髄運動ニューロンにおけるα-synuclein、PINK1、DJ-1の発現について
    森本 展年, 宮崎 一徳, 倉田 智子, 池田 佳生, 松浦 徹, 阿部 康二 臨床神経学 51 (12) 1361 -1361 2011年12月 [査読無し][通常論文]
  • Kota Sato, Taijun Yunoki, Nobutoshi Morimoto, Shoko Nagotani, Kentaro Deguchi, Yasushi Takehisa, Yoshio Ikeda, Toru Matsuura, Koji Abe, Yuji Yamamoto European Journal of Neurology 18 (8) e100 -e101 2011年08月 [査読無し][通常論文]
  • Hiromi Kawai, Toru Yamashita, Yasuyuki Ohta, Kentaro Deguchi, Shoko Deguchi, Xuemei Zhang, Yoshio Ikeda, Tohru Matsuura, Koji Abe NEUROSCIENCE RESEARCH 68 E358 -E358 2010年 [査読無し][通常論文]
  • Kazunori Miyazaki, Makiko Nagai, Nobutoshi Morimoto, Tomoko Kurata, Yasuyuki Ohta, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Koji Abe NEUROSCIENCE RESEARCH 68 E95 -E95 2010年 [査読無し][通常論文]
  • Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage.
    Lukic-Panin V, Deguchi K, Yamashita T, Shang J, Zhang X, Tian F, Liu N, Kawai H, Matsuura T, Abe K Curr Neurovasc Res. 7 (4) 319 -329 2010年 [査読無し][通常論文]
  • Yasuyuki Ohta, Makiko Nagai, Nobutoshi Morimoto, Kazunori Miyazaki, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Sadamitsu Asoh, Shigeo Ohra, Koji Abe ANNALS OF NEUROLOGY 66 S17 -S17 2009年 [査読無し][通常論文]
  • Nobutoshi Morimoto, Makiko Nagai, Kazunori Miyazaki, Yasuyuki Ohta, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Koji Abe NEUROSCIENCE RESEARCH 65 S120 -S120 2009年 [査読無し][通常論文]
  • Yasuyuki Ohta, Makiko Nagai, Nobutoshi Morimoto, Kazunori Miyazaki, Yasushi Takehisa, Yoshio Ikeda, Tohru Matsuura, Sadamitsu Asoh, Shigeo Ohta, Koji Abe ANNALS OF NEUROLOGY 66 S64 -S64 2009年 [査読無し][通常論文]
  • RH Walker, A Rasmussen, D Rudnicki, G Bosman, SE Holmes, E Alonso, T Matsuura, T Ashizawa, B Davidoff-Feldman, RL Margolis JOURNAL OF THE NEUROLOGICAL SCIENCES 229 358 -358 2005年03月 [査読無し][通常論文]
  • R Gao, Lin, X, W Xu, T Matsuura, T Ashizawa MOVEMENT DISORDERS 19 (9) 1123 -1123 2004年09月 [査読無し][通常論文]
  • P Fang, HAG Teive, Alonso, I, L Jardim, J Sequeiros, Silveira, I, S Raskin, E Schmitt, PA Ward, T Matsuura, T Ashizawa, BB Roa AMERICAN JOURNAL OF HUMAN GENETICS 73 (5) 585 -585 2003年11月 [査読無し][通常論文]
  • P Fang, T Matsuura, HAG Teive, S Raskin, P Jayakar, E Schmitt, T Ashizawa, BB Roa AMERICAN JOURNAL OF HUMAN GENETICS 71 (4) 552 -552 2002年10月 [査読無し][通常論文]
  • KJ Swoboda, BW Soong, C McKenna, ERP Brunt, M Litt, JF Bale, T Ashizawa, LB Bennett, AM Bowcock, ES Roach, D Gerson, T Matsuura, PT Heydemann, MP Nespeca, J Jankovic, M Leppert, LJ Ptacek NEUROLOGY 57 (11) S42 -S48 2001年12月 [査読無し][通常論文]
     
    Objective: To clinically characterize affected individuals in families with paroxysmal kinesigenic dyskinesia (PEM), examine the association with infantile convulsions, and confirm linkage to a pericentromeric chromosome 16 locus. Background: PKD is characterized by frequent, recurrent attacks of involuntary movement or posturing in response to sudden movement, stress, or excitement. Recently, an autosomal dominant PKD locus on chromosome 16 was identified. Methods: The authors studied 11 previously unreported families of diverse ethnic background with PKD with or without infantile convulsions and performed linkage analysis with markers spanning the chromosome 16 locus. Detailed clinical questionnaires and interviews were conducted with affected and unaffected family members. Results: Clinical characterization and sampling of 95 individuals in 11 families revealed 44 individuals with paroxysmal dyskinesia, infantile convulsions, or both. Infantile convulsions were surprisingly common, occurring in 9 of 11 families. In only two individuals did generalized seizures occur in later childhood or adulthood. The authors defined a 26-cM region using linkage data in 11 families (maximum lod score 6.63 at Theta = 0). Affected individuals in one family showed no evidence for a shared haplotype in this region, implying locus heterogeneity. Conclusions: Identification and characterization of the PKD/infantile convulsions gene will provide new insight into the pathophysiology of this disorder, which spans the phenotypic spectrum between epilepsy and movement disorder.
  • P Fang, W Jin, T Matsuura, T Ashizawa, BB Roa AMERICAN JOURNAL OF HUMAN GENETICS 69 (4) 651 -651 2001年10月 [査読無し][通常論文]
  • T Matsuura, P Fang, A Rasmussen, RP Grewal, ME Alonso, BB Roa, T Ashizawa AMERICAN JOURNAL OF HUMAN GENETICS 69 (4) 652 -652 2001年10月 [査読無し][通常論文]
  • T Matsuura, DL Burgess, T Yamagata, A Rasmussen, RP Grewal, K Watase, K Tsuji, M Khajavi, A McCall, CF Davis, P Yescas, L Zu, SM Pulst, E Alonso, JL Noebels, DL Nelson, HY Zoghbi, T Ashizawa AMERICAN JOURNAL OF HUMAN GENETICS 67 (4) 55 -55 2000年10月 [査読無し][通常論文]
  • T Ashizawa, T Matsuura, A Rasmussen, RP Grewal, L Zu, SM Pulst, M Pandolfo, H Sasaki, Volpini, V, T Yamagata, K Watase, DL Burgess, K Inoue, P Yescas, S Nagamitsu, MY Momoi, K Tashiro, HY Zoghbi, E Alonso, DL Nelson AMERICAN JOURNAL OF HUMAN GENETICS 67 (4) 373 -373 2000年10月 [査読無し][通常論文]
  • A Rasmussen, P Yescas, T Matsuura, T Ashizawa, M Alonso AMERICAN JOURNAL OF HUMAN GENETICS 67 (4) 342 -342 2000年10月 [査読無し][通常論文]
  • T Matsuura, T Yamagata, DL Burgress, A Rasmussen, RP Grewal, K Watase, M Khajavi, L Zu, SM Pulst, E Alonso, JL Noebels, DL Nelson, HY Zoghbi, T Ashizawa ANNALS OF NEUROLOGY 48 (3) 416 -416 2000年09月 [査読無し][通常論文]
  • EK Tan, T Matsuura, S Nagamitsu, M Khajavi, J Jankovic, T Ashizawa AMERICAN JOURNAL OF HUMAN GENETICS 65 (4) A469 -A469 1999年10月 [査読無し][通常論文]
  • T Matsuura, M Khajavi, R de Silva, T Ashizawa AMERICAN JOURNAL OF HUMAN GENETICS 65 (4) A460 -A460 1999年10月 [査読無し][通常論文]
  • S Nagamitsu, T Matsuura, M Khajavi, R Armstrong, C Gooch, T Ashizawa AMERICAN JOURNAL OF HUMAN GENETICS 65 (4) A482 -A482 1999年10月 [査読無し][通常論文]
  • S Nagamitsu, T Matsuura, M Khajavi, R Armstrong, C Gooch, T Ashizawa ANNALS OF NEUROLOGY 46 (3) 462 -462 1999年09月 [査読無し][通常論文]
  • T Matsuura, K Watase, S Nagamitsu, HY Zoghbi, T Ashizawa ANNALS OF NEUROLOGY 46 (3) 480 -481 1999年09月 [査読無し][通常論文]
  • Yabe, I, H Sasaki, T Matsuura, A Takada, A Wakisaka, T Hamada, K Tashiro ANNALS OF NEUROLOGY 42 (3) T249 -T249 1997年09月 [査読無し][通常論文]
  • T Matsuura, H Sasaki, A Wakisaka, F Moriwaka, T Yoshiki, K Tashiro ANNALS OF NEUROLOGY 40 (3) T163 -T163 1996年09月 [査読無し][通常論文]
  • A OGATA, T MATSUURA, T DEMURA, F MORIWAKA, K TASHIRO, T KOYANAGI, K NAGASHIMA NEUROLOGY 43 (4) A319 -A319 1993年04月 [査読無し][通常論文]
  • T. Yamada, K. Tashiro, F. Moriwaka, N. Fujiki, K. Ito, S. Honma, T. Matsuura, S. Doi Brain and Nerve 41 (6) 583 -588 1989年 [査読無し][通常論文]
  • A WAKISAKA, H SASAKI, T KATOH, MC YOSHIDA, T HAMADA, K SHIMA, T MATSUURA, T TAKENOUCHI, K TASHIRO CYTOGENETICS AND CELL GENETICS 51 (1-4) 1101 -1101 1989年 [査読無し][通常論文]

産業財産権

  • DNA TEST FOR SCA-10
    USPTO#6,885,497
  • DNA TEST FOR SCA-10
    USPTO#6,885,497

受賞

  • 2007年 日本神経学会2007年度「学会賞」学術研究分野
     JPN
  • 2003年 Young Investigator Award, National Ataxia Foundation
  • 2003年 Young Investigator Award, National Ataxia Foundation

共同研究・競争的資金等の研究課題

  • ロングリードシーケンサーを用いた筋強直性ジストロフィー2型伸長リピート構造の解明
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2020年04月 -2023年03月 
    代表者 : 松浦 徹
  • 脆弱X随伴振戦/失調症候群(FXTAS)における症状改善薬の開発
    国立研究開発法人日本医療研究開発機構:難治性疾患実用化研究事業
    研究期間 : 2017年04月 -2020年03月 
    代表者 : 塩田 倫史
  • 脆弱X症候群ならびに脆弱X随伴振戦/失調症候群の治療推進に向けた臨床基盤整備の研究班
    国立研究開発法人日本医療研究開発機構:難治性疾患実用化研究事業
    研究期間 : 2015年04月 -2018年03月 
    代表者 : 難波 栄二
  • 非翻訳領域リピート病のリピート異常翻訳と不安定性メカニズム
    文部科学省科学研究費:挑戦的萌芽研究
    研究期間 : 2014年04月 -2017年03月 
    代表者 : 松浦 徹
  • 非翻訳領域リピート伸長脊髄小脳失調症のリピート不安定機構とRNA解析
    文部科学省科学研究費:基盤研究 (B)
    研究期間 : 2012年04月 -2016年03月 
    代表者 : 松浦 徹
  • 筋強直性ジストロフィーの神経特異的スプライシング異常と治療への展開
    文部科学省科学研究費:挑戦的萌芽研究
    研究期間 : 2011年04月 -2014年03月 
    代表者 : 松浦 徹
  • 非翻訳リピート病-SCA10・DM2異常伸長リピートRNAの代謝制御
    文部科学省科学研究費:新学術領域研究(課題型)
    研究期間 : 2008年04月 -2011年03月 
    代表者 : 松浦 徹
  • 優性遺伝性非翻訳リピート病の異常スプライシング病態研究
    文部科学省科学研究費:基盤研究 (C)
    研究期間 : 2007年04月 -2009年03月 
    代表者 : 松浦 徹
  • 脊髄小脳変性症10型の神経変性とインスタビリティ-機構
    文部科学省科学研究費:特定領域研究 (公募)
    研究期間 : 2006年04月 -2008年03月 
    代表者 : 松浦 徹

委員歴

  • 2014年 - 現在   日本神経治療学会   評議員
  • 2013年 - 現在   日本神経学会   代議員
  • 2011年 - 現在   日本人類遺伝学会   評議員


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