Researchers Database

morita mitsuya

    Rehabilitation Professor
Last Updated :2021/12/07

Researcher Information

Degree

  • MD(1995/03 Jichi Medical University)

Research funding number

  • 30343445

J-Global ID

Research Interests

  • 運動ニューロン疾患   リハビリテーション   人類遺伝学   神経内科学   Genetics   Neurology   

Research Areas

  • Life sciences / Neurology
  • Life sciences / Rehabilitation science

Academic & Professional Experience

  • 2021/07 - Today  Jichi Medical University HospitalRehabilitation CenterProfessor
  • 2009/04 - Today  Jichi Medical University HospitalRehabilitation
  • 2017/01 - 2021/06  Jichi Medical UniversityDepartment of Internal Medicine, Division of Neurology/ Rehabilitation CenterAssociate Professor

Association Memberships

  • European Academy of Neurology   日本リハビリテーション医学会   日本内科学会   日本人類遺伝学会   日本神経学会   日本神経免疫学会   日本遺伝カウンセリング学会   日本神経治療学会   

Published Papers

  • Ryoichi Nakamura, Kazuharu Misawa, Genki Tohnai, Masahiro Nakatochi, Sho Furuhashi, Naoki Atsuta, Naoki Hayashi, Daichi Yokoi, Hazuki Watanabe, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Kazuaki Kanai, Nobutaka Hattori, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Kazumoto Shibuya, Satoshi Kuwabara, Naoki Suzuki, Masashi Aoki, Yasuyuki Ohta, Toru Yamashita, Koji Abe, Rina Hashimoto, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Yohei Okada, Tomohiko Ishihara, Osamu Onodera, Kenji Nakashima, Ryuji Kaji, Yoichiro Kamatani, Shiro Ikegawa, Yukihide Momozawa, Michiaki Kubo, Noriko Ishida, Naoko Minegishi, Masao Nagasaki, Gen Sobue
    Communications Biology 3 (1) 2020/12 
    Abstract Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.
  • 日本におけるSOD1遺伝子変異陽性筋萎縮性側索硬化症患者の臨床的特徴
    中村 亮一, 熱田 直樹, 藤内 玄規, 林 直毅, 勝野 雅央, 和泉 唯信, 金井 数明, 服部 信孝, 谷口 彰, 森田 光哉, 狩野 修, 澁谷 和幹, 桑原 聡, 鈴木 直輝, 青木 正志, 阿部 康二, 石原 智彦, 小野寺 理, 梶 龍兒, 祖父江 元
    臨床神経学 (一社)日本神経学会 60 (Suppl.) S381 - S381 0009-918X 2020/11
  • 多施設共同前向きコホートでみたALS患者の非侵襲的人工換気療法に関する予後の検討
    林 直毅, 熱田 直樹, 横井 大知, 中村 亮一, 勝野 雅央, 和泉 唯信, 金井 数明, 服部 信孝, 谷口 彰, 森田 光哉, 狩野 修, 澁谷 和幹, 桑原 聡, 鈴木 直輝, 青木 正志, 織田 雅也, 饗場 郁子, 梶 龍兒, 祖父江 元
    臨床神経学 (一社)日本神経学会 60 (Suppl.) S381 - S381 0009-918X 2020/11
  • Magdalena Kuźma-Kozakiewicz, Peter M Andersen, Elahe Elahi, Afagh Alavi, Peter C Sapp, Mitsuya Morita, Cezary Żekanowski, Mariusz Berdyński
    Amyotrophic lateral sclerosis & frontotemporal degeneration 1 - 6 2020/08 [Refereed][Not invited]
     
    Mutations in SOD1 cause approximately 12-25% of familial ALS and ≈2% of apparently sporadic ALS cases. Clinical phenotypes linked to SOD1 mutations are heterogeneous and intra-familial variability of the clinical phenotype is frequently observed. SOD1 L144S mutation, identified also in Brazil, Iran and United States, is the second most frequent mutation among ALS patients in Poland. So far, 10 FALS pedigrees with SOD1 L144S mutation have been reported worldwide. The aim of the study was to establish the origin of SOD1 L144S mutation in geographically distinct populations. The clinical presentation of the Polish patients was compared with those from the previously reported populations (26 ever-reported patients). Clinically, L144S mutation is associated with both sporadic and familial ALS of relatively slow uniform course, a prevalent onset in the lower limbs, either classic or PMA presentation and a long survival time. Like in the case of other previously described SOD1 mutations, there was an intra-familial heterogeneity and reduced penetrance for ALS was observed. We propose that the L144S SOD1 mutation in the three studied populations has a common founder most likely of Polish origin.
  • Ryoichi Nakamura, Genki Tohnai, Naoki Atsuta, Masahiro Nakatochi, Naoki Hayashi, Hazuki Watanabe, Daichi Yokoi, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Akira Taniguchi, Kazuaki Kanai, Mitsuya Morita, Osamu Kano, Satoshi Kuwabara, Masaya Oda, Koji Abe, Masashi Aoki, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Nobutaka Hattori, Kenji Nakashima, Ryuji Kaji, Gen Sobue
    Neurobiology of Aging 0197-4580 2020/07
  • Naoki Hayashi, Naoki Atsuta, Daichi Yokoi, Ryoichi Nakamura, Masahiro Nakatochi, Masahisa Katsuno, Yuishin Izumi, Kazuaki Kanai, Nobutaka Hattori, Akira Taniguchi, Mitsuya Morita, Osamu Kano, Kazumoto Shibuya, Satoshi Kuwabara, Naoki Suzuki, Masashi Aoki, Ikuko Aiba, Kouichi Mizoguchi, Masaya Oda, Ryuji Kaji, Gen Sobue
    Journal of neurology, neurosurgery, and psychiatry 91 (3) 285 - 290 2020/03 [Refereed][Not invited]
     
    OBJECTIVE: The aim of this study is to describe and clarify the factors affecting the prognosis of Japanese patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy invasive ventilation (TIV) therapy. METHODS: We conducted a prospective longitudinal observational case-control study using a multicentre registry. ALS patients who started TIV therapy after registration (TIV group) and those who did not receive TIV (non-TIV group) were included. We compared the survival time between the TIV group and the non-TIV group using a propensity score matching analysis and evaluated the prognostic factors in the TIV group. RESULTS: From February 2006 to January 2018, 190 patients in the TIV group and 1093 patients in the non-TIV group were included in this study. The mean age of disease onset and usage rate of gastrostomy and non-invasive ventilation therapy differed between the groups. In the propensity score matching analysis using known prognostic factors, the median overall survival time of the TIV group was significantly greater than that of the non-TIV group (11.33 years vs 4.61 years; p<0.001). Analysis using the Cox proportional hazard model suggested that older age of onset and respiratory onset was an independent factor for poor prognosis after starting TIV therapy. CONCLUSION: We showed that there was a significant difference of approximately 7 years in life expectancy between Japanese ALS patients who did and did not receive TIV therapy.
  • ALS患者の生存期間に与える非侵襲的換気補助療法の影響 レジストリを用いた解析
    熱田 直樹, 横井 大知, 平川 晃弘, 林 直毅, 中村 良一, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 狩野 修, 桑原 聡, 青木 正志, 金井 数明, 小野寺 理, 梶 龍兒, 祖父江 元, JaCALS
    臨床神経学 (一社)日本神経学会 59 (Suppl.) S358 - S358 0009-918X 2019/11
  • Hashizume Atsushi, Katsuno Masahisa, Suzuki Keisuke, Banno Haruhiko, Takeuchi Yu, Kawashima Motoshi, Suga Noriaki, Mano Tomoo, Araki Amane, Hijikata Yasuhiro, Hirakawa Akihiro, Sobue Gen, Sasaki H, Aoki M, Nakano I, Ito S, Mizusawa H, Yamamoto To, Hasegawa K, Miyajima H, Kanda N, Nakajima K, Tsujino A, Uchino M, Morita M, Kanai K
    JOURNAL OF NEUROLOGY 266 (5) 1211-1221 - 1221 0340-5354 2019/05 [Not refereed][Not invited]
     
    BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. METHODS: Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began. RESULTS: The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups. CONCLUSIONS: The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
  • Kensuke Ikenaka, Naoki Atsuta, Yasuhiro Maeda, Yuji Hotta, Ryoichi Nakamura, Kaori Kawai, Daichi Yokoi, Akihiro Hirakawa, Akira Taniguchi, Mitsuya Morita, Kouichi Mizoguchi, Hideki Mochizuki, Kazunori Kimura, Masahisa Katsuno, Gen Sobue
    Neurology 92 (16) e1868-e1877  2019/04 [Refereed][Not invited]
     
    OBJECTIVE: To investigate whether arginine methylation is altered in patients with amyotrophic lateral sclerosis (ALS) and how it affects disease severity, progression, and prognosis. METHODS: We compared the immunoreactivity of protein arginine methyltransferase 1 (PRMT1) and its products, asymmetric dimethylated proteins (ASYM), in postmortem spinal cord. We also measured the concentrations of total l-arginine and methylated arginine residues, including asymmetric dimethyl l-arginine (ADMA), symmetric dimethyl arginine, and monomethyl arginine, in CSF samples from 52 patients with ALS using liquid chromatography-tandem mass spectrometry, and we examined their relationship with the progression and prognosis of ALS. RESULTS: The immunoreactivity of both PRMT1 (p < 0.0001) and ASYM (p = 0.005) was increased in patients with ALS. The concentration of ADMA in CSF was substantially higher in patients with ALS than in disease controls. The ADMA/l-arginine ratio was correlated with the change of decline in the ALS Functional Rating Scale at 12 months after the time of measurement (r = 0.406, p = 0.010). A Cox proportional hazards model showed that the ADMA/l-arginine ratio was an independent predictor for overall survival. Moreover, a high ADMA/l-arginine ratio predicted poor prognosis, even in a group with normal percentage forced vital capacity. CONCLUSION: There was an enhancement of arginine dimethylation in patients with ALS, and the ADMA/l-arginine ratio predicted disease progression and prognosis in such patients.
  • Takeshi Sakurada, Aya Goto, Masayuki Tetsuka, Takeshi Nakajima, Mitsuya Morita, Shin-Ichiroh Yamamoto, Masahiro Hirai, Kensuke Kawai
    Neurophotonics 6 (2) 025012 - 025012 2019/04 [Refereed][Not invited]
     
    Directing attention to movement outcomes (external focus; EF), not body movements (internal focus; IF), is a better cognitive strategy for motor performance. However, EF is not effective in some healthy individuals or stroke patients. We aimed to identify the neurological basis reflecting the individual optimal attentional strategy using functional near-infrared spectroscopy. Sixty-four participants (23 healthy young, 23 healthy elderly, and 18 acute stroke) performed a reaching movement task under IF and EF conditions. Of these, 13 healthy young participants, 11 healthy elderly participants, and 6 stroke patients showed better motor performance under EF conditions (EF-dominant), whereas the others showed IF-dominance. We then measured prefrontal activity during rhythmic hand movements under both attentional conditions. IF-dominant participants showed significantly higher left prefrontal activity than EF-dominant participants under IF condition. In addition, receiver operating characteristic analysis supported that the higher activity in the left frontopolar and dorsolateral prefrontal cortices could detect IF-dominance as an individual's optimal attentional strategy for preventing motor performance decline. Taken together, these results suggest that prefrontal activity during motor tasks reflects an individual's ability to process internal body information, thereby conferring IF-dominance. These findings could be applied for the development of individually optimized rehabilitation programs.
  • 多施設共同前向きコホートでみたALS患者に対する気管切開下陽圧換気療法の予後
    林 直毅, 熱田 直樹, 横井 大知, 中村 亮一, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 饗場 郁子, 狩野 修, 谷口 彰, 森田 光哉, 阿部 康二, 金井 数明, 服部 信孝, 青木 正志, 桑原 聡, 梶 龍兒, 祖父江 元, JaCALS
    臨床神経学 (一社)日本神経学会 58 (Suppl.) S347 - S347 0009-918X 2018/12
  • Hajime Tanabe, Yujiro Higuchi, Jun-Hui Yuan, Akihiro Hashiguchi, Akiko Yoshimura, Satoshi Ishihara, Satoshi Nozuma, Yuji Okamoto, Eiji Matsuura, Hiroyuki Ishiura, Jun Mitsui, Ryotaro Takashima, Norito Kokubun, Kengo Maeda, Yuri Asano, Yoko Sunami, Yu Kono, Yasunori Ishigaki, Shosaburo Yanamoto, Jiro Fukae, Hiroshi Kida, Mitsuya Morita, Shoji Tsuji, Hiroshi Takashima
    Journal of the Peripheral Nervous System 23 (1) 40 - 48 1529-8027 2018/03 [Refereed][Not invited]
     
    Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders.
  • Hemophagocytic Lymphohistiocytosis Associated with Scrub Typhus: Systematic Review and Comparison between Pediatric and Adult Cases
    Naoi Tameto, Morita Mitsuya, Kawakami Tadataka, Fujimoto Shigeru
    Tropical Medicine and Infectious Disease 3 (1) 2018/02 [Refereed][Not invited]
  • Ikeda A, Funayama M, Yoshida M, Conedera S, Li Y, Nishioka K, Aiba I, Saito Y, Atsuta N, Nakamura R, Tohnai G, Sone J, Lzumi Y, Kaji R, Morita M, Taniguchi A, Sobue G, Hattori N
    JOURNAL OF THE NEUROLOGICAL SCIENCES 381 104-104  0022-510X 2017/10 [Not refereed][Not invited]
  • Atsuta N, Yokoi D, Nakamura R, Watanabe H, Hayashi N, Ito M, Watanabe H, Katsuno M, Izumi Y, Morita M, Taniguchi A, Oda M, Abe K, Mizoguchi K, Kano O, Kuwabara S, Aoki M, Hattori N, Kaji R, Sobue G
    JOURNAL OF THE NEUROLOGICAL SCIENCES 381 103-103  0022-510X 2017/10 [Not refereed][Not invited]
  • Angelica Nordin, Chizuru Akimoto, Anna Wuolikainen, Helena Alstermark, Karin Forsberg, Peter Baumann, Susana Pinto, Mamede De Carvalho, Annemarie Huebers, Frida Nordin, Albert C. Ludolph, Jochen H. Weishaupt, Thomas Meyer, Torsten Grehl, Kathi Schweikert, Markus Weber, Christian Burkhardt, Christoph Neuwirth, Trygve Holmoy, Mitsuya Morita, Ole-Bjorn Tysnes, Michael Benatar, Joanne Wuu, Dale J. Lange, Carsten Bisgard, Nasrin Asgari, Ilkka Tarvainen, Thomas Brannstrom, Peter M. Andersen
    AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION 18 (3-4) 256 - 264 2167-8421 2017 [Refereed][Not invited]
     
    A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n=6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n=6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n=473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele.In conclusion, we identified 38 different sequence variants, most located within the first 50bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
  • 脳卒中患者の認知運動機能連関に関する個人差とその神経基盤
    櫻田武, 後藤彩, 中嶋剛, 森田光哉, 平井真洋, 山本紳一郎, 渡辺英寿, 川合謙介
    機能的脳神経外科 56 62 - 67 2017 [Not refereed][Invited]
  • Takeshi Sakurada, Takeshi Nakajima, Mitsuya Morita, Masahiro Hirai, Eiju Watanabe
    SCIENTIFIC REPORTS 7 :40592  2045-2322 2017/01 [Refereed][Not invited]
     
    It is believed that motor performance improves when individuals direct attention to movement outcome (external focus, EF) rather than to body movement itself (internal focus, IF). However, our previous study found that an optimal individual attentional strategy depended on motor imagery ability. We explored whether the individual motor imagery ability in stroke patients also affected the optimal attentional strategy for motor control. Individual motor imagery ability was determined as either kinesthetic- or visual-dominant by a questionnaire in 28 patients and 28 healthy-controls. Participants then performed a visuomotor task that required tracing a trajectory under three attentional conditions: no instruction (NI), attention to hand movement (IF), or attention to cursor movement (EF). Movement error in the stroke group strongly depended on individual modality dominance of motor imagery. Patients with kinesthetic dominance showed higher motor accuracy under the IF condition but with concomitantly lower velocity. Alternatively, patients with visual dominance showed improvements in both speed and accuracy under the EF condition. These results suggest that the optimal attentional strategy for improving motor accuracy in stroke rehabilitation differs according to the individual dominance of motor imagery. Our findings may contribute to the development of tailor-made pre-assessment and rehabilitation programs optimized for individual cognitive abilities.
  • Koji Abe, Masashi Aoki, Shoji Tsuji, Yasuto Itoyama, Gen Sobue, Masanori Togo, Chikuma Hamada, Hidenao Sasaki, Lchiro Yabe, Shizuki Doi, Hitoshi Warita, Takashi Lmai, Hiroaki Ito, Mitsumasa Fukuchi, Etsuko Osumi, Manabu Wada, Lmaharu Nakanol, Mitsuya Morita, Katsuhisa Ogata, Yuichi Maruki, Kimiko Ito, Osamu Kano, IViineo Yamazaki, Yuji Takahashi, Hiroyuki Ishiura, Micko Ogino, Ryoko Koike, Chiho Ishida, Tsuyoshi Uchiyama, Koichi Mizoguchi, Tomokazu Obi, Hirohisa Watanabe, Naoki Atsuta, Ikuko Aiba, Akira Taniguchi, Hideyuki Sawada, Takanori Hazama, Harutoshi Fujimura, Hirofumi Kusaka, Takenobu Kunieda, Hiroshi Kikuchi, Hidenori Matsuo, Hidetsug-U Ueyama, Kazutoshi Uekawa, Masahiko Tanaka, Makoto Akimoto, Kazue Nakamura, Masaki Ueda, Kuniko Kotani, Hiroshi Matsui, Takatomo Yoneoka, Kazunori Morimoto, Kouichi Sasaki, Nianabu Hirai, Aiko Murakami, Tomoko Natori, Rie Sumii, Hidetomo Terai, Takuya Kudou, Fumihiro Takahashi, Tomohisa Iwasaki, Kazuoki Kondo, Hiide Yoshino
    AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION 18 (10) 55 - 63 2167-8421 2017 [Refereed][Not invited]
     
    We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores >2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-12], forced vital capacity >80%, definite or probable ALS, and disease duration <2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was 4.1 +/- 3.4 and 6.9 +/- 5.1 in the E-E group and P-E group, respectively, while it was 8.0 +/- 5.6 in the E-E group and 10.9 perpendicular to 16.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.
  • ALS患者に対する換気補助療法の予後
    横井 大知, 熱田 直樹, 渡辺 はづき, 中村 亮一, 平川 晃弘, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 阿部 康二, 溝口 功一, 狩野 修, 桑原 聡, 梶 龍兒, 祖父江 元, JaCALS
    臨床神経学 (一社)日本神経学会 56 (Suppl.) S524 - S524 0009-918X 2016/12
  • 孤発性筋萎縮性側索硬化症患者における発症年齢と遺伝学的背景に関する検討
    中村 亮一, 曽根 淳, 熱田 直樹, 藤内 玄規, 横井 大知, 中杤 昌弘, 渡辺 宏久, 伊藤 瑞規, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 服部 信孝, 織田 雅也, 狩野 修, 桑原 聡, 阿部 康二, 梶 龍兒, 祖父江 元, JaCALS
    臨床神経学 (一社)日本神経学会 56 (Suppl.) S414 - S414 0009-918X 2016/12 [Refereed][Not invited]
  • Daichi Yokoi, Naoki Atsuta, Hazuki Watanabe, Ryoichi Nakamura, Akihiro Hirakawa, Mizuki Ito, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Masaya Oda, Koji Abe, Kouichi Mizoguchi, Osamu Kano, Satoshi Kuwabara, Ryuji Kaji, Gen Sobue
    Journal of Neurology 263 (6) 1129 - 1136 1432-1459 2016/06 [Refereed][Not invited]
     
    The clinical courses of sporadic amyotrophic lateral sclerosis (ALS) show extensive variability. Our objective was to elucidate how age of onset influences the progression of regional symptoms and functional losses in sporadic ALS. We included 648 patients with sporadic ALS from a multicenter prospective ALS cohort. We investigated the distribution of initial symptoms and analyzed the time from onset to events affecting activities of daily living (ADL) as well as the longitudinal changes in each regional functional rating score among four groups with different ages of onset. The frequencies of dysarthria and dysphagia as initial symptoms were higher in the older age groups, whereas weakness of upper limbs was the most common initial symptom in the youngest age group. The survival times and the times from onset to loss of speech and swallowing were significantly shorter in the older age group (p <  0.001), although the times from onset to loss of upper limb function were not significantly different among the age groups. According to joint modeling analysis, the bulbar score declined faster in the older age groups (< 50 vs. 60–69 years: p = 0.029, < 50 vs. ≥70 years: p <  0.001), whereas there was no significant correlation between the age of onset and decline in the upper limb score. Our results showed that age of onset had a significant influence on survival time and the progression of bulbar symptoms, but had no influence on upper limb function in sporadic ALS.
  • Ryoichi Nakamura, Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS), Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Masashi Aoki, Nobutaka Hattori, Shoji Tsuji, Kenji Nakashima, Ryuji Kaji, Gen Sobue
    Neurobiology of Aging 39 219 - 219.e8 1558-1497 2016/03 [Refereed][Not invited]
     
    We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients.
  • 球脊髄性筋萎縮症患者に対するリュープロレリン酢酸塩長期使用の効果
    橋詰 淳, 勝野 雅央, 鈴木 啓介, 坂野 晴彦, 須賀 徳明, 矢部 一郎, 青木 正志, 森田 光哉, 金井 数明, 水澤 英洋, 山本 知孝, 長谷川 一子, 西澤 正豊, 宮嶋 裕明, 苅田 典生, 中島 健二, 辻野 彰, 内野 誠, 田中 章景, 祖父江 元
    臨床神経学 (一社)日本神経学会 55 (Suppl.) S200 - S200 0009-918X 2015/12
  • 我が国のALS患者に対する換気補助療法の現状と予後 多施設共同ALSコホートの解析から
    渡辺 はづき, 熱田 直樹, 平川 晃弘, 中村 亮一, 横井 大知, 渡辺 宏久, 伊藤 瑞規, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 狩野 修, 溝口 功一, 阿部 康二, 桑原 聡, 梶 龍兒, 祖父江 元, Jacals
    臨床神経学 (一社)日本神経学会 55 (Suppl.) S377 - S377 0009-918X 2015/12
  • 孤発性ALSに対して発症年齢が自然歴に与える影響
    横井 大知, 熱田 直樹, 渡辺 はづき, 中村 亮一, 平川 晃弘, 伊藤 瑞規, 渡辺 宏久, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 阿部 康二, 溝口 功一, 狩野 修, 桑原 聡, 梶 龍兒, 祖父江 元, Jacals
    臨床神経学 (一社)日本神経学会 55 (Suppl.) S379 - S379 0009-918X 2015/12
  • TFG変異による運動ニューロン疾患
    瓦井 俊孝, 森田 光哉, 沖 良祐, 森垣 龍馬, 藤田 浩司, 川田 明広, 大垣 光太郎, 谷藤 誠司, 小泉 英貴, 村上 永尚, 野寺 裕之, 大崎 裕亮, Banzrai Chimeglkham, Orlacchio Antonio, 田邉 彬恵, 長谷川 真梨子, 高橋 明美, 和泉 唯信, 後藤 惠, 梶 龍兒
    臨床神経学 (一社)日本神経学会 55 (Suppl.) S132 - S132 0009-918X 2015/12 [Refereed][Not invited]
  • 熱田 直樹, 渡辺 はづき, 中村 亮一, 横井 大知, 渡辺 宏久, 伊藤 瑞規, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 狩野 修, 溝口 功一, 阿部 康二, 桑原 聡, 梶 龍兒, 祖父江 元
    神経治療学 (一社)日本神経治療学会 32 (5) 773 - 773 0916-8443 2015/09
  • Hazuki Watanabe, Naoki Atsuta, Ryoichi Nakamura, Akihiro Hirakawa, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Yuishin Izumi, Mitsuya Morita, Hiroyuki Tomiyama, Akira Taniguchi, Ikuko Aiba, Koji Abe, Kouichi Mizoguchi, Masaya Oda, Osamu Kano, Koichi Okamoto, Satoshi Kuwabara, Kazuko Hasegawa, Takashi Imai, Masashi Aoki, Shoji Tsuji, Imaharu Nakano, Ryuji Kaji, Gen Sobue
    Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 16 (3-4) 230 - 236 2167-9223 2015/06 [Refereed][Not invited]
     
    Our objective was to elucidate the clinical factors affecting functional decline and survival in Japanese amyotrophic lateral sclerosis (ALS) patients. We constructed a multicenter prospective ALS cohort that included 451 sporadic ALS patients in the analysis. We longitudinally utilized the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) as the functional scale, and determined the timing of introduction of a tracheostomy for positive-pressure ventilation and death. A joint modelling approach was employed to identify prognostic factors for functional decline and survival. Age at onset was a common prognostic factor for both functional decline and survival (p < 0.001, p < 0.001, respectively). Female gender (p = 0.019) and initial symptoms, including upper limb weakness (p = 0.010), lower limb weakness (p = 0.008) or bulbar symptoms (p = 0.005), were related to early functional decline, whereas neck weakness as an initial symptom (p = 0.018), non-use of riluzole (p = 0.030) and proximal dominant muscle weakness in the upper extremities (p = 0.01) were related to a shorter survival time. A decline in the ALSFRS-R score was correlated with a shortened survival time (p < 0.001). In conclusion, the factors affecting functional decline and survival in ALS were common in part but different to some extent. This difference has not been previously well recognized but is informative in clinical practice and for conducting trials.
  • ALSの進行を規定する因子の探索同定
    熱田 直樹, 渡辺 はづき, 中村 亮一, 平川 晃弘, 中杤 昌弘, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 和泉 唯信, 梶 龍兒, 森田 光哉, 富山 弘幸, 谷口 彰, 溝口 功一, 狩野 修, 阿部 康二, 中野 今治, 池川 志郎, 飯田 有俊, 祖父江 元
    臨床神経学 (一社)日本神経学会 54 (Suppl.) S69 - S69 0009-918X 2014/12
  • ALS患者におけるADL低下と生存へ影響する因子の検討 多施設共同ALSコホートの解析から
    渡辺 はづき, 熱田 直樹, 中村 亮一, 平川 晃弘, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 和泉 唯信, 森田 光哉, 富山 弘幸, 谷口 彰, 溝口 功一, 狩野 修, 桑原 聡, 阿部 康二, 梶 龍兒, 中野 今治, 祖父江 元
    臨床神経学 (一社)日本神経学会 54 (Suppl.) S149 - S149 0009-918X 2014/12
  • Yuriko Doi, Naoki Atsuta, Gen Sobue, Mitsuya Morita, Imaharu Nakano
    JOURNAL OF EPIDEMIOLOGY 24 (6) 494 - 499 0917-5040 2014/11 [Refereed][Not invited]
     
    Background: Previous studies have reported a high incidence of amyotrophic lateral sclerosis (ALS) in endemic foci in the Kii Peninsula, Japan. However, little is known about the ALS frequency in the whole country. Furthermore, the presence of ethnic variation in the incidence of ALS remains unknown. Methods: We conducted a nationwide survey of ALS frequency in 2013 to estimate its annual prevalence and incidence. ALS was diagnosed based on the El Escorial Criteria. The study period was the 2009 fiscal year, from April 2009 to March 2010. To compare the incidence of ALS among prefectures, standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated under the assumption of Poisson distribution. Results: The annual crude prevalence and incidence rates per 100 000 people per year were 9.9 (95% CI 9.7-10.1) and 2.2 (95% CI 2.1-2.3), respectively. The age group with the highest prevalence as well as incidence was 70-79 years, and the male-female ratio was approximately 1.5. The annual incidence rate adjusted for age and sex using the 2000 U. S. standard population was 2.3 (95% CI 2.2-2.4) per 100 000 people. Some prefectures had significantly high SIRs: Okinawa, Nara and Wakayama in the Kii Peninsula, and Niigata for males; Kumamoto for females. Conclusions: This is the first report on the annual prevalence and incidence of ALS in the representative population of Japan. We identified some prefectures with a high incidence of ALS. However, the incidence of ALS in the Japanese population was much lower than in the Caucasian populations of Europe and North America.
  • Judith Rabkin, Mieko Ogino, Raymond Goetz, Martin McElhiney, Jonathan Hupf, Daragh Heitzman, Terry Heiman-Patterson, Robert Miller, Jonathan Katz, Catherine Lomen-Hoerth, Takashi Imai, Naoki Atsuta, Mitsuya Morita, Takahisa Tateishi, Tsuyoshi Matsumura, Hiroshi Mitsumoto
    Amyotrophic lateral sclerosis & frontotemporal degeneration 15 (3-4) 185 - 91 2167-8421 2014/06 [Refereed][Not invited]
     
    Substantial disparities in TIV utilization rates among ALS patients have been observed, with rates in Japan far exceeding rates in the United States. Our objective was to elicit national preferences and their determinants. We predicted more Japanese than American patients would desire TIV, as would sicker patients, those already using non-invasive interventions, and those with more positive mood and outlook. Patients were enrolled in five U.S. states and six Japanese regions. Eligible patients completed surveys during clinic visits (U.S.) or at home (Japan). Survey responses were in multiple-choice format and took about 15 min to complete. One hundred and fifty-six Americans and 66 Japanese patients participated. Contrary to expectations, Japanese patients were more likely to oppose TIV, as were those on 24-h NIV and patients who knew someone using TIV. Most Japanese and American patients with advanced respiratory impairment were undecided or opposed to TIV, while nearly 20% in both countries were in favor. Finally, patients who favored TIV or who were undecided had more energy, greater wish to live, and more sense of control over ALS management. In conclusion, factors other than patient preferences, such as neurologist preferences, caregiver attitudes and perhaps lack of advance planning, may influence probability of TIV utilization.
  • Akihiko Miyauchi, Yukifumi Monden, Meri Watanabe, Hideo Sugie, Mitsuya Morita, Takeshi Kezuka, Mariko Momoi, Takanori Yamagata
    NEUROPEDIATRICS 45 (3) 196 - 199 0174-304X 2014/06 [Refereed][Not invited]
     
    We report the case of a 5-year-old Japanese girl who initially had acute disseminated encephalomyelitis (ADEM) and was positive for the myelin oligodendrocyte glycoprotein (MOG) antibodies and developed unilateral optic neuritis (ON) 71 days after ADEM onset. The patient's serum was positive for the anti-MOG antibodies from the onset of ADEM to the development of ON. This phenotype has been reported in only two previous articles, and the specific mechanism of action of the anti-MOG antibodies is not yet understood. Our case suggests that the anti-MOG antibody can be associated with the pathogenesis of ADEM followed by ON. Thus, patients with ADEM who test positive for the anti-MOG antibody may be at risk of developing subsequent ON.
  • Syuichi Tetsuka, Kaoru Tominaga, Eriko Ohta, Kenji Kuroiwa, Eiji Sakashita, Katsumi Kasashima, Toshiro Hamamoto, Michito Namekawa, Mitsuya Morita, Shinsuke Natsui, Tatsuo Morita, Keiko Tanaka, Yoshihisa Takiyama, Imaharu Nakano, Hitoshi Endo
    Journal of the Neurological Sciences 335 (1-2) 48 - 57 0022-510X 2013/12 [Refereed][Not invited]
     
    Onconeural immunity, a cancer-stimulated immune reaction that cross-reacts with neural tissues, is considered to be the principal pathological mechanism for paraneoplastic neurological syndromes (PNS). A common PNS is paraneoplastic cerebellar degeneration (PCD). We had encountered a PCD patient with urothelial carcinomas (UC) of the urinary bladder who was negative for the well-characterized PNS-related onconeural antibodies. In the present study, we aimed to identify a new PCD-related onconeural antibody, capable of recognizing both cerebellar neurons and cancer tissues from the patient, and applied a proteomic approach using mass spectrometry. We identified anti-creatine kinase, brain-type (CKB) antibody as a new autoantibody in the serum and cerebrospinal fluid from the patient. Immunohistochemistry indicated that anti-CKB antibody reacted with both cerebellar neurons and UC of the urinary bladder tissues. However, anti-CKB antibody was not detected in sera from over 30 donors, including bladder cancer patients without PCD, indicating that anti-CKB antibody is required for onset of PCD. We also detected anti-CKB antibody in sera from three other PCD patients. Our study demonstrated that anti-CKB antibody may be added to the list of PCD-related autoantibodies and may be useful for diagnosis of PCD. © 2013 Elsevier B.V. All rights reserved.
  • 頸部屈筋の筋力低下はALSにおける独立した予後予測指標である
    中村 亮一, 熱田 直樹, 渡辺 はづき, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 平川 晃弘, 和泉 唯信, 梶 龍兒, 森田 光哉, 富山 弘幸, 谷口 彰, 溝口 功一, 岡本 幸市, 長谷川 一子, 青木 正志, 中野 今治, 祖父江 元
    臨床神経学 (一社)日本神経学会 53 (12) 1412 - 1412 0009-918X 2013/12
  • Magdalena Kuźma-Kozakiewicz, Mariusz Berdyński, Mitsuya Morita, Yuji Takahashi, Akihiro Kawata, Ken-Ichi Kaida, Beata Kaźmierczak, Anna Łusakowska, Jun Goto, Shoji Tsuji, Cezary Zekanowski, Hubert Kwieciński
    Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 14 (7-8) 608 - 614 2167-8421 2013/12 [Refereed][Not invited]
     
    Cu/Zn superoxide dismutase (SOD1) gene mutations are the most frequently reported genetic causes of amyotrophic lateral sclerosis (ALS). The objective of the study was to describe a clinical phenotype and haplotype background of Polish and Japanese ALS patients harbouring the K3E SOD1 mutation. The K3E mutation was identified by direct sequencing, high resolution melting analysis or high-throughput microarray-based resequencing system. Microsatellite polymorphic markers flanking SOD1 were genotyped in members of six kindreds and two SALS patients. Results demonstrated that the K3E mutation was responsible for classic ALS. The median age of onset was 54 years. The clinical phenotype did not substantially differ between SALS and FALS cases of either ethnic origin, with some intrafamiliar variabilities. There was a limb onset in 92% of patients. In patients with bulbar syndrome, dysphagia predominated over dysarthria. Respiratory insufficiency was found in 61.1% of patients (19-84 months after the first symptoms onset). Median survival was 101 months with age of death ranging from 45 to 77 years. K3E was the most frequent SOD1 mutation among Polish FALS patients. It originated independently, on different haplotype background in the Polish and Japanese populations. In conclusion, recurrent K3E mutation results in a relatively slowly progressing limb onset ALS with classic phenotype. © 2013 Informa Healthcare.
  • S. Tetsuka, M. Morita, K. Ikeguchi, I. Nakano
    Acta Neurologica Scandinavica 128 (6) 386 - 390 0001-6314 2013/12 [Refereed][Not invited]
     
    Objectives: Creatinine (Cr) as a marker of renal function has limited value in amyotrophic lateral sclerosis (ALS) because patients with ALS have reduced muscle mass. Thus, there is a need for alternative methods of assessing renal function. Cystatin C (CysC), which is unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity in ALS however, its utility requires validation. Material and Methods: One hundred and six subjects were recruited for the study: 76 ALS patients and 30 healthy controls. We compared the Cr-based estimated glomerular filtration rate (eGFR) with the CysC-based eGFR in the ALS patients and healthy controls. The results were further analysed according to the severity of ALS in the patients. Results: The mean Cr-based eGFRs were 257.2 ± 383.1 ml/min/1.73 m2 in the ALS group and 98.1 ± 34.9 in the control group however, the mean CysC-based eGFRs were not significantly different between both groups. Thus, the Cr-based eGFR in the ALS group was markedly higher than any of the other values. Although serum CysC levels did not correlate with the severity of ALS according to the ALS Functional Rating Scale-Revised, strong simple correlations were observed between serum Cr levels and the severity of ALS (correlation coefficient = 0.734, P < 0.001). Conclusions: This study demonstrates the potential usefulness of CysC as a biomarker of renal function in ALS patients. Furthermore, its applicability could be extended to other neuromuscular diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
  • Kotaro Kawanishi, Mitsuya Morita, Keiichi Nakahara, Syuichi Tetsuka, Tom Kouki, Kaoru Tominaga, Hitoshi Endo, Takashi Yashiro, Keiko Tanaka, Imaharu Nakano
    Brain and Nerve 65 (11) 1401 - 1405 1881-6096 2013/11 [Refereed][Not invited]
     
    A 66-year-old man was diagnosed with bladder cancer at our urology department. Three months later, he developed subacute progressive cerebellar limb ataxia and truncal oscillation. Analysis of cerebrospinal fluid showed pleocytosis and increased concentrations of protein, while brain magnetic resonance imaging revealed no abnormalities. Based on the presence of the bladder cancer, the etiology of subacute cerebellar ataxia could be a paraneoplastic neurological syndrome. Four months later, the patient underwent transurethral resection of the bladder tumor, which was identified as urothelial cancer on the basis of pathological examinations. However, this procedure failed to improve his neurological symptoms. Serum paraneoplastic markers such as anti-Yo, anti-Hu, anti-Tr, and other antibodies were not detected. Immunohistochemical staining of mouse cerebellum using the patient's serum revealed coarse granular staining in the cytoplasm of Purkinje cells and diffuse staining in the neuropil of the molecular layer, suggesting the presence of an unknown antibody. Subsequently, one-dimensional electrophoresis western blotting using the patient's serum revealed several bands including a strong positive band of approximately 45 kDa in mouse cerebellum lysates but not in liver lysates. These bands have never been detected in sera derived from healthy donors. These results suggested the presence of a novel antibody in the patient's serum that might recognize the approximately 45 kDa protein related to paraneoplastic cerebellar degeneration. Cases of paraneoplastic neurological syndrome associated with bladder cancer have rarely been reported. We concluded that the present case may be categorized as paraneoplastic neurological syndrome caused by an unknown antibody.
  • Toshiaki Takahashi, Masashi Aoki, Naoki Suzuki, Maki Tateyama, Chikako Yaginuma, Hitomi Sato, Miho Hayasaka, Hitomi Sugawara, Mariko Ito, Emi Abe-Kondo, Naoko Shimakura, Tohru Ibi, Satoshi Kuru, Tadashi Wakayama, Gen Sobue, Naoki Fujii, Toshio Saito, Tsuyoshi Matsumura, Itaru Funakawa, Eiichiro Mukai, Toru Kawanami, Mitsuya Morita, Mineo Yamazaki, Takashi Hasegawa, Jun Shimizu, Shoji Tsuji, Shigeki Kuzuhara, Hiroyasu Tanaka, Masaru Yoshioka, Hidehiko Konno, Hiroshi Onodera, Yasuto Itoyama
    Journal of neurology, neurosurgery, and psychiatry 84 (4) 433 - 40 2013/04 [Refereed][Not invited]
     
    OBJECTIVE AND METHODS: Dysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed. RESULTS AND CONCLUSIONS: Three mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.
  • David Czell, Peter M. Andersen, Christoph Neuwirth, Mitsuya Morita, Markus Weber
    AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION 14 (2) 138 - 140 2167-8421 2013/03 [Refereed][Not invited]
  • Judith Rabkin, Mieko Ogino, Raymond Goetz, Martin McElhiney, Allison Marziliano, Takashi Imai, Naoki Atsuta, Mitsuya Morita, Takahisa Tateishi, Tsuyoshi Matsumura, Hiroshi Mitsumoto
    AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION 14 (2) 116 - 123 2167-8421 2013/03 [Refereed][Not invited]
     
    Our objective was to determine whether substantial differences in rates of TIV utilization in the U. S. and Japan are associated with the role of the treating neurologist. Questionnaires in English and Japanese were sent to neurologists who treated ALS patients in both countries. Questions included queries about rates of TIV use in their practices, level of encouragement of TIV use, the role of the neurologist in TIV decision making, management of patient/family requests to discontinue TIV once initiated, and personal choices if neurologists themselves had ALS. Results showed that 84% of American neurologists reported fewer than 10% of their patients had TIV, compared to 32% of Japanese. Americans less often encouraged TIV use (79% of American and 36% of Japanese seldom or never suggested or encouraged TIV). Finally, neurologists were asked whether they would choose TIV for themselves in the hypothetical scenario where they had ALS: over 70% of both groups declined TIV for themselves. In conclusion, consistent with past findings, Japanese neurologists were more likely to recommend TIV and more of their patients received TIV. Both groups believed their recommendations influence patient decisions. While Americans seldom recommended TIV to patients and most would not choose TIV for themselves, Japanese neurologists' recommendations and personal choices diverged.
  • 近赤外線分光計側を用いた重度障害者向けユーザーインターフェース
    木戸邦彦, 森田光哉, 長尾雅裕, 小沢邦昭, 内藤正美, 牧 敦
    レーザー研究 41 (8) 622 - 626 2013 [Refereed][Not invited]
  • Creatinine/cystatin C ratio as a surrogate marker of residual muscle mass in Amyotrophic lateral sclerosis.
    S. Tetsuka, M. Morita, K. Ikeguchi, I. Nakano
    Neurology and Clinical Neuroscience. 1 (1) 32 - 37 2013 [Refereed][Not invited]
  • Syuichi Tetsuka, Mitsuya Morita, Aritoshi Iida, Ritei Uehara, Shiro Ikegawa, Imaharu Nakano
    JOURNAL OF THE NEUROLOGICAL SCIENCES 324 (1-2) 163 - 166 0022-510X 2013/01 [Refereed][Not invited]
     
    Recently, Iida et al. discovered a new single-nucleotide polymorphism (SNP) in the ZNF512B gene associated with susceptibility to amyotrophic lateral sclerosis (ALS). The ZNF512B gene was found to be a transcription factor promoting the expression of a downstream gene in the signal transduction pathway of the transforming growth factor-beta (TGF-beta), which is essential for the protection and survival of neurons but the influence of the new SNP (rs2275294) in actual ALS patients remained unknown. The objective of our study was to examine whether the new SNP in the ZNF512B gene might influence the phenotype of ALS. We conducted a retrospective analysis of the ZNF512B gene in 176 patients diagnosed as having ALS at our hospital. Evaluation of the prognosis after the onset using Kaplan-Meier survival curves in patients with versus without the risk allele (C allele: CC and CT genotypes) revealed a significantly lower survival probability in those with the risk allele (log-rank test, P<0.01), independent of the other prognostic factors in ALS. Our study revealed the influence of the new SNP in actual ALS patients. It would be clinically reasonable to suggest that the ZNF512B gene is a new prognostic factor in ALS. This study is the first, as per our knowledge, to indicate that the association between the new susceptibility gene for ALS and its pathway could be identified. (C) 2012 Elsevier B.V. All rights reserved.
  • Toshitaka Kawarai, Mitsuya Morita, Ryoma Morigaki, Koji Fujita, Hiroyuki Nodera, Yuishin Izumi, Satoshi Goto, Imaharu Nakano, Ryuji Kaji
    Clinical Neurology 53 (11) 1199  0009-918X 2013 [Refereed][Not invited]
     
    Mutations in TFG gene have been demonstrated in hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) and hereditary spastic paraplegia (HSP). A broad spectrum of TFG pathology is suspected in motor neuron diseases including amyotrophic lateral sclerosis (ALS). We performed mutation screening of TFG gene in ALS cases and evaluated the biological functions of mutant TFG by expression experiment in cultured cells. Two missense mutations associated with sporadic ALS were discovered. Mislocalization of ALS-related proteins, including TDP-43 and optineurin, was demonstrated. These results indicate that mistrafficking of ALS-related proteins by mutant TFG might be a biological cascade leading to motor neuron death.
  • Ryoichi Nakamura, Naoki Atsuta, Hazuki Watanabe, Akihiro Hirakawa, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuishin Izumi, Mitsuya Morita, Kotaro Ogaki, Akira Taniguchi, Ikuko Aiba, Koichi Mizoguchi, Koichi Okamoto, Kazuko Hasegawa, Masashi Aoki, Akihiro Kawata, Koji Abe, Masaya Oda, Masaaki Konagaya, Takashi Imai, Masanori Nakagawa, Shoji Tsuji, Ryuji Kaji, Imaharu Nakano, Gen Sobue
    Journal of Neurology, Neurosurgery and Psychiatry 84 (12) 1365 - 1371 1468-330X 2013 [Refereed][Not invited]
     
    Objective: To clarify the emergence of muscle weakness in regions of the body that affect survival, and deterioration in activities of daily living (ADL) in amyotrophic lateral sclerosis (ALS) patients. Methods: We conducted a multicentre-based prospective cohort study of patients with ALS. We enrolled 401 sporadic patients with ALS. Death or the introduction of invasive ventilation was defined as the primary endpoint, and the time to five clinical markers of ADL deterioration associated with bulbar paralysis or limb weakness were defined as ADL milestones. Muscle weakness was assessed in the neck flexor muscles the bilateral abductors of the shoulders the bilateral wrist extensor muscles the bilateral flexor muscles of the hips and the bilateral ankle dorsi flexion muscles. We performed Cox proportional hazards regression analyses for the primary endpoint and the five ADL milestones, adjusting for known covariate prognostic factors for ALS. Results: The Medical Research Council (MRC) score for the neck flexors was the most significant prognostic factor for the primary endpoint (HR 0.74, p< 0.001), loss of speech (HR 0.66, p< 0.001), and loss of swallowing function (HR 0.73, p< 0.001), and was one of the significant prognostic factors for loss of upper limb function, difficulty turning in bed , and loss of walking ability ( p=0.001, 0.002, and 0.008, respectively). The MRC score for the neck flexors was also a significant prognostic factor for covariates of the previously reported prognostic factors. Conclusions: Neck weakness is an independent prognostic factor for survival and deterioration in ADL in Patients with ALS.
  • 抗神経抗体の存在が確認できた膀胱癌を伴う傍腫瘍性小脳変性症の1例
    川西康太郎, 森田光哉, 中原圭一, 手塚修一, 幸喜 富, 冨永 薫, 遠藤仁司, 屋代 隆, 田中惠子, 中野今治
    Brain Nerve 65 (11) 1401 - 1405 2013 [Refereed][Not invited]
  • 当院におけるZNF512B遺伝子を持つALS患者についての検討
    手塚 修一, 森田 光哉, 飯田 有俊, 池川 志郎, 中村 祐輔, 中野 今治
    臨床神経学 (一社)日本神経学会 52 (12) 1549 - 1549 0009-918X 2012/12
  • ALS患者の縦断像 JaCALSからの解析
    中村 亮一, 熱田 直樹, 渡辺 はづき, 千田 譲, 伊藤 瑞規, 渡辺 宏久, 田中 章景, 梶 龍兒, 和泉 唯信, 森田 光哉, 青木 正志, 溝口 功一, 谷口 彰, 岡本 幸市, 饗場 郁子, 川田 明広, 長谷川 一子, 大垣 光太郎, 中野 今治, 祖父江 元
    臨床神経学 (一社)日本神経学会 52 (12) 1519 - 1519 0009-918X 2012/12
  • Kotaro Ogaki, Yuanzhe Li, Naoki Atsuta, Hiroyuki Tomiyama, Manabu Funayama, Hazuki Watanabe, Ryoichi Nakamura, Hideo Yoshino, Seiji Yato, Asako Tamura, Yutaka Naito, Akira Taniguchi, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Nobutaka Hattori, Gen Sobue
    NEUROBIOLOGY OF AGING 33 (10) e11 - e16 0197-4580 2012/10 [Refereed][Not invited]
     
    Recently, a hexanucleotide repeat expansion in C9orf72 was identified as the most common cause of both sporadic and familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Western populations. We analyzed 563 Japanese patients with ALS (552 sporadic and 11 familial) using fluorescent fragment-length analysis of C9orf72 and repeat-primed polymerase chain reaction analysis. Haplotype analysis was performed for 42 single nucleotide polymorphisms in patients with C9orf72 repeat expansion. C9orf72 repeat expansion was found in 2 patients with sporadic ALS (2/552 = 0.4%) and no patients with familial ALS (0/11 = 0%). In the probands' families, 1 primary progressive aphasia patient and 1 asymptomatic 76-year-old individual exhibited C9orf72 repeat expansion. All of the patients with the C9orf72 repeat expansion carried the 20-single nucleotide polymorphism consensus risk haplotype. The frequency of the C9orf72 repeat expansion among Japanese patients is much lower than in Western populations. The existence of a 76-year-old asymptomatic carrier supported the notion of incomplete penetrance. The C9orf72 mutation should be analyzed in sporadic ALS patients after determining their family histories not only of frontotemporal dementia but also of primary progressive aphasia. (C) 2012 Elsevier Inc. All rights reserved.
  • 髄液PCR陰性であったが脳生検で確定診断した進行性多巣性白質脳症の1例
    直井 為任, 森田 光哉, 齊藤 寛大, 嶋崎 晴雄, 藤本 健一, 中道 一生, 中野 今治
    NEUROINFECTION 日本神経感染症学会 16 (2) 155 - 155 1348-2718 2011/10 [Refereed][Not invited]
  • Aritoshi Iida, Atsushi Takahashi, Michiaki Kubo, Susumu Saito, Naoya Hosono, Yozo Ohnishi, Kazuma Kiyotani, Taisei Mushiroda, Masahiro Nakajima, Kouichi Ozaki, Toshihiro Tanaka, Tatsuhiko Tsunoda, Shuichi Oshima, Motoki Sano, Tetsumasa Kamei, Torao Tokuda, Masashi Aoki, Kazuko Hasegawa, Koichi Mizoguchi, Mitsuya Morita, Yuji Takahashi, Masahisa Katsuno, Naoki Atsuta, Hirohisa Watanabe, Fumiaki Tanaka, Ryuji Kaji, Imaharu Nakano, Naoyuki Kamatani, Shoji Tsuji, Gen Sobue, Yusuke Nakamura, Shiro Ikegawa
    HUMAN MOLECULAR GENETICS 20 (18) 3684 - 3692 0964-6906 2011/09 [Refereed][Not invited]
     
    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Several susceptibility genes for ALS have been reported; however, ALS etiology and pathogenesis remain largely unknown. To identify further ALS-susceptibility genes, we conducted a large-scale case-control association study using gene-based tag single-nucleotide polymorphisms (SNPs). A functional SNP (rs2275294) was found to be significantly associated with ALS through a stepwise screening approach (combined P = 9.3 x 10(-10), odds ratio = 1.32). The SNP was located in an enhancer region of ZNF512B, a transcription factor of unknown biological function, and the susceptibility allele showed decreased activity and decreased binding to nuclear proteins. ZNF512B over-expression increased transforming growth factor-beta (TGF-beta) signaling, while knockdown had the opposite effect. ZNF512B expression was increased in the anterior horn motor neurons of the spinal cord of ALS patients when compared with controls. Our results strongly suggest that ZNF512B is an important positive regulator of TGF-beta signaling and that decreased ZNF512B expression increases susceptibility to ALS.
  • Aritoshi Iida, Atsushi Takahashi, Min Deng, Yun Zhang, Jing Wang, Naoki Atsuta, Fumiaki Tanaka, Tetsumasa Kamei, Motoki Sano, Shuichi Oshima, Torao Tokuda, Mitsuya Morita, Chizuru Akimoto, Masahiro Nakajima, Michiaki Kubo, Naoyuki Kamatani, Imaharu Nakano, Gen Sobue, Yusuke Nakamura, Dongsheng Fan, Shiro Ikegawa
    NEUROBIOLOGY OF AGING 32 (4) e13 - e14 0197-4580 2011/04 [Refereed][Not invited]
     
    We performed a replication study of the 2 genetic variants, rs2814707 on 9p21.2 and rs12608932 on 19p13.3 that are recently reported to be most significantly associated with sporadic amyotrophic lateral sclerosis (ALS) in Caucasians. Both rs12608932 and rs2814707 showed no evidence of association in Japanese and Chinese (rs12608932, combined p = 0.58, odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.93-1.13; rs2814707, combined p = 0.88, OR = 1.10, 95% CI 0.93-1.30). The association of these loci with susceptibility to sporadic ALS is considered negative in East Asians. (C) 2011 Elsevier Inc. All rights reserved.
  • Banno Haruhiko, Katsuno Masahisa, Suzuki Keisuke, Takeuchi Yu, Kawashima Motoshi, Yabe Ichiro, Sasaki Hidenao, Aoki Masashi, Morita Mitsuya, Nakano Imaharu, Kanai Kazuaki, Ito Shoichi, Ishikawa Kinya, Mizusawa Hidehiro, Yamamoto Tomotaka, Tsuji Shoji, Hasegawa Kazuko, Shimohata Takayoshi, Nishizawa Masatoyo, Miyajima Hiroaki, Kanda Fumio, Watanabe Yasuhiro, Nakashima Kenji, Tsujino Akira, Yamashita Taro, Uchino Makoto, Fujimoto Yasushi, Tanaka Fumiaki, Sobue Gen
    NEUROLOGY 76 (9) A583  0028-3878 2011/03 [Refereed][Not invited]
  • Chizuru Akimoto, Mitsuya Morita, Naoki Atsuta, Gen Sobue, Imaharu Nakano
    Neurology research international 2011 165415 - 165415 2011 [Refereed][Not invited]
     
    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and the majority of ALS are sporadic (SALS). Recently, several causative genes for familial ALS (FALS) were identified, but the cause of the SALS is still unknown. This time, we aimed to identify the genetic background of SALS. First, we applied the new sensitive screening methods: high-resolution melting (HRM) analysis. HRM analysis detected 18 out of 19 known SOD1 gene mutations (94.7% sensitivity). Next, we screened SOD1, three novel mutations (C6Y, Q22H, and S134T) were identified in our own 184 SALS cases (1.63% prevalence), and four mutations in another 255 SALS cases (1.56% prevalence) registered from all over Japan. The patients with SOD1 mutations suggested a relatively young onset and limb involvement at onset. The HRM analysis is a sensitive and easy screening method; we will use this method for screening other ALS causative genes and revealing the genetic background of SALS.
  • Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Yu Takeuchi, Motoshi Kawashima, Ichiro Yabe, Hidenao Sasaki, Masashi Aoki, Mitsuya Morita, Imaharu Nakano, Kazuaki Kanai, Shoichi Ito, Kinya Ishikawa, Hidehiro Mizusawa, Tomotaka Yamamoto, Shoji Tsuji, Kazuko Hasegawa, Takayoshi Shimohata, Masatoyo Nishizawa, Hiroaki Miyajima, Fumio Kanda, Yasuhiro Watanabe, Kenji Nakashima, Akira Tsujino, Taro Yamashita, Makoto Uchino, Yasushi Fujimoto, Fumiaki Tanaka, Gen Sobue
    LANCET NEUROLOGY 9 (9) 875 - 884 1474-4422 2010/09 [Refereed][Not invited]
     
    Background Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor. At present there are no treatments for spinal and bulbar muscular atrophy, although leuprorelin suppressed the accumulation of pathogenic androgen receptors in a phase 2 trial. We aimed to assess the efficacy and safety of leuprorelin for spinal and bulbar muscular atrophy. Methods The Japan SBMA Interventional Trial for TAP-144-SR (JASMITT) was a 48-week, randomised, double-blind, placebo-controlled trial done at 14 hospitals between August, 2006, and March, 2008. Patients with spinal and bulbar muscular atrophy were randomly assigned (1:1) by minimisation to subcutaneous 11.25 mg leuprorelin or identical placebo every 12 weeks. Patients and investigators were masked to treatment allocation. The primary endpoint was pharyngeal barium residue, which indicates incomplete bolus clearance, measured at week 48 by videofluorography. All patients who were randomly assigned and who were assessed with videofluorography at least once were included in the analyses. This study is registered with the JMACCT clinical trials registry, number JMA-IIA00009, and the UMIN clinical trials registry, number UMIN000000465. Findings 204 patients were randomly assigned and 199 started treatment: 100 with leuprorelin and 99 with placebo. At week 48, the pharyngeal barium residue after initial swallowing had changed by -5.1% (SD 21.0) in the leuprorelin group and by 0.2% (18.2) in the placebo group (difference between groups -5.3%; 95% CI -10.8 to 0.3; p=0.063). The mean difference in pharyngeal barium residue after piecemeal deglutition at week 48 was -3.2% (-6.4 to 0.0; p=0.049), but there was no significant difference between the groups after covariate adjustment for the baseline data (-4.1 to 1.6; p=0.392). In a predefined subgroup analysis, leuprorelin treatment was associated with a greater reduction in barium residue after initial swallowing than was placebo in patients with a disease duration less than 10 years (difference between groups -9.8, -17.1 to -2.5; p=0.009). There were no significant differences in the number of drug-related adverse events between groups (57 of 100 in the leuprorelin group and 54 of 99 in the placebo group; p=0.727). Interpretation 48 weeks of treatment with leuprorelin did not show significant effects on swallowing function in patients with spinal and bulbar muscular atrophy, although it was well tolerated. Disease duration might influence the efficacy of leuprorelin and thus further clinical trials with sensitive outcome measures should be done in subpopulations of patients.
  • 膝に関する症状を自発的に訴えた高齢者群と訴えなかった高齢者群の比較検討.
    高橋恒存, 笹沼秀幸, 松村福広, 森田光哉
    運動療法と物理療法 21 (3) 247 - 254 2010 [Refereed][Not invited]
  • 脊髄損傷ラットにおける補助歩行訓練後の神経原性疼痛と発症機序の検討
    遠藤照顕, 井上泰一, 木村敦, 安食孝士, 中間季雄, 森田光哉, 関矢仁, 星野雄一
    21 (3) 279 - 284 2010 [Refereed][Not invited]
  • 秋本千鶴, 森田光哉, 中野今治
    臨床神経学 50 399 - 403 2010 [Refereed][Not invited]
  • 人工膝関節置換術後の10m歩行時間と下肢筋力
    関矢仁, 川合直美, 本間朋恵, 高田尚, 杉本直哉, 森田光哉
    運動療法と物理療法 20 251 - 254 2009 [Refereed][Not invited]
  • 安藤喜仁, 澤田幹雄, 森田光哉, 河村満, 中野今治森田
    臨床神経学 49 560 - 565 2009 [Refereed][Not invited]
  • Haruo Shimazaki, Mitsuya Morita, Imaharu Nakano, Josep Dalmau
    ARCHIVES OF NEUROLOGY 65 (9) 1251 - 1251 0003-9942 2008/09 [Not refereed][Not invited]
  • 典型的なneuromyelitis optica(NMO)の病変に加え、大小脳白質と脳幹にも病変が散在する抗アクアポリン4(AQP4)抗体陽性の35歳女性例
    熊谷 祐子, 手塚 修一, 森田 光哉, 滑川 道人, 中野 今治
    臨床神経学 (一社)日本神経学会 48 (8) 601 - 601 0009-918X 2008/08
  • Masato Hasegawa, Tetsuaki Ara, Takashi Nonaka, Fuyuki Kametani, Mari Yoshida, Yoshio Hashizume, Thomas G. Beach, Emanuele Buratti, Francisco Baralle, Mitsuya Morita, Imaharu Nakano, Tatsuro Oda, Kuniaki Tsuchiya, Haruhiko Akiyama
    ANNALS OF NEUROLOGY 64 (1) 60 - 70 0364-5134 2008/07 [Not refereed][Not invited]
     
    Objective: TAR DNA-binding protein of 43kDa (TDP-43) is deposited as cytoplasmic and intranuclear inclusions in brains of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Previous studies reported that abnormal phosphorylation takes place in deposited TDP-43. The aim of this study was to identify the phosphorylation sites and responsible kinases, and to clarify the pathological significance of phosphorylation of TDP-43. Methods: We generated multiple antibodies specific to phosphorylated TDP-43 by immunizing phosphopeptides of TDP-43, and analyzed FTLD-U and ALS brains by immunohistochemistry, immunoelectron microscopy, and immunoblots. In addition, we performed investigations aimed at identifying the responsible kinases, and we assessed the effects of phosphorylation on TDP-43 oligomerization and fibrillization. Results: We identified multiple phosphorylation sites in carboxyl-terminal regions of deposited TDP-43. Phosphorylation-specific antibodies stained more inclusions than antibodies to ubiquitin and, unlike existing commercially available anti-TDP-43 antibodies, did not stain normal nuclei. Ultrastructurally, these antibodies labeled abnormal fibers of 15nm diameter and on immunoblots recognized hyperphosphorylated TDP-43 at 45kDa, with additional 18 to 26kDa fragments in sarkosyl-insoluble fractions from FTLD-U and ALS brains. The phosphorylated epitopes were generated by casein kinase-1 and -2, and phosphorylation led to increased oligomerization and fibrillization of TDP-43. Interpretation: These results suggest that phosphorylated TDP-43 is a major component of the inclusions, and that abnormal phosphorylation of TDP-43 is a critical step in the pathogenesis of FTLD-U and ALS. Phosphorylation-specific antibodies will be powerful tools for the investigation of these disorders.
  • Tetsuaki Arai, Masato Hasegawa, Masugi Nishihara, Takashi Nonaka, Fuyuki Kametani, Mari Yoshida, Yoshio Hashizume, Thomas G. Beach, Mitsuya Morita, Imaharu Nakano, Tatsuro Oda, Kuniaki Tsuchiya, Haruhiko Akiyama
    Clinical Neurology 48 (11) 990 - 993 0009-918X 2008 [Refereed][Not invited]
     
    Research on familial frontotemporal lobar degeneration (FTLD) has led to the discovery of disease-causing genes: microtubule-associated protein tau (MAPT), progranulin (PGRN) and valosin-containing protein (VCP). TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as a major component of tau-negative ubiquitin-positive inclusions in familial and sporadic FTLD and amyotrophic lateral sclerosis (ALS), which are now referred to as TDP-43 proteinopathy. Recent findings of mutations in TDP-43 gene in familial and sporadic ALS cases confirm the pathogenetic role for TDP-43 in neurodegeneration. TDP43 proteinopathies have been classified into 4 pathological subtypes. Type 1 is characterized by numerous dystrophic neurites (DNs), Type 2 has numerous neuronal cytoplasmic inclusions (NCIs), Type 3 has NCIs and DNs and Type 4 has neuronal intranuclear inclusions (NIIs) and DNs. There is a close relationship between such pathological subtypes of TDP-43 proteinopathy and the immunoblot pattern of C-terminal fragments of accumulated TDP-43. These results parallel our earlier findings of differing C-terminal tau fragments in progressive supranuclear palsy and corticobasal degeneration, despite identical composition of tau isoforms. Taken together, these results suggest that elucidating the mechanism of C-terminal fragment origination may shed light on the pathogenesis of several neurodegenerative disorders involving TDP43 proteinopathy and tauopathy.
  • Masato Hasegawa, Tetsuaki Arai, Takashi Nonaka, Fuyuki Kametani, Mari Yoshida, Yoshio Hashizume, Thomas G. Beach, Mitsuya Morita, Imaharu Nakano, Tatsuro Oda, Kuniaki Tsuchiya, Haruhiko Akiyama
    Clinical Neurology 48 (11) 994 - 997 0009-918X 2008 [Refereed][Not invited]
     
    Tau-negative and ubiquitin-positive inclusions (UPI) are the pathological hallmarks of frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, TDP-43, a heterogeneous nuclear ribonucleoprotein was identified as a component of these UPI. However, it remains to be determined whether TDP-43 is the major component of UPI, because only antibodies recognizing both normal and abnormal TDP-43 have been available. We raised antibodies to phosphopeptides representing 36 out of 64 candidate phosphorylation sites of human TDP-43. Of the generated antibodies, pS379, pS403/404, pS409, pS410 and pS409/410 clearly labeled UPI and glial cytoplasmic inclusions but not the nuclei. Immunoblot analyses of sarkosyl insoluble fractions demonstrated that the phosphorylation-specific antibodies recognized TDP-43 at -45 kDa, smearing substances and the -25 kDa fragment, all of which were present in the brains of FTLD-U and ALS but not controls. These antibodies did not recognize normal TDP-43 at 43 kDa. These results clearly indicate that abnormally phosphorylated full-length TDP-43 and the C-terminal fragments are the major component of UPI in FTLD-U and ALS. These findings together with recent discovery of mutations in the TDP-43 gene in ALS strongly suggest that TDP-43 is the key molecule responsible for neurodegeneration in FTLD-U and ALS.
  • T. Ishikawa, M. Morita, I. Nakano
    ACTA NEUROLOGICA SCANDINAVICA 116 (5) 340 - 344 0001-6314 2007/11 [Not refereed][Not invited]
     
    Objectives - We investigated the regional cerebral blood flow in amyotrophic lateral sclerosis with dementia (ALS-D) patients, using single photon emission computed tomography (SPECT). Materials and methods - The I-123-IMP SPECT data for 5 ALS-D and 16 ALS patients were analyzed using three-dimensional stereotactic surface projection (3D-SSP). Results - 3D-SSP demonstrated marked prefrontal hypoperfusion in all the five ALS-D cases and significant bilateral prefrontal hypoperfusion in group comparisons. Conclusions - This study revealed prefrontal hypoperfusion in ALS-D cases to be an obvious abnormality with scientific objectivity.
  • Mami Fukunaga, Yasumasa Ohyagi, Mitsuya Morita, Hiroshi Shigeto, Takayuki Taniwaki, Jun-Ichi Kira
    Clinical Neurology 47 (6) 359 - 361 0009-918X 2007/06 [Refereed][Not invited]
     
    We report a 73-year-old man with SPG4. From aged 53 he had diabetes mellitus and at 64 he developed spastic paraparesis and urinary disturbance. At 70 years, he began to walk with a stick and noted abnormal sensations in bilateral feet. There was no relevant family history. Moderate spasticity with mild muscle weakness, markedly brisk tendon reflex with pathological reflexes, and mildly abnormal sensation in bilateral lower extremities, and markedly spastic gait were found. MRI showed mild C4-C7 spondylosis and L4-5 disk protrusion but no abnormality of the corpus callosum. Nerve conduction and needle EMG studies revealed various abnormalities in distal (MCV, SCV) and proximal (F-wave) peripheral nerves, but no neurogenic changes in limb muscles. We found a missense spastin gene mutation (1726T> C) that causes Leu534Pro substitution. This spastin gene mutation was novel in Japanese, but has been reported in an Italian family. The present case's neuropathy might be related to diabetes mellitus, because SPG4 is generally not associated with neuropathy. However, recent studies suggest that SPG4 patients sometimes have subclinical neuropathy, and longer disease duration may contribute to peripheral neuropathy. Further study of clinical characteristics associated with the Leu534Pro mutation will be necessary.
  • Chizuru Kawamata, Mitsuya Morita, Noriyuki Shibata, Imaharu Nakano
    Clinical Neurology 47 (5) 211 - 216 0009-918X 2007/05 [Refereed][Not invited]
     
    We describe a patient with familial amyotrophic lateral sclerosis (FALS) in whom we identified a substitution of G for CGTTTA at codon 144 in the Cu/Zn superoxide dismutase 1 (SOD1) gene, causing amino acid changes from leucine to phenylalanine, valine and a stop codon (L144FVX). This mutation is novel, and so we report the clinical and neuropathological features of this case compared with those of other FALS cases with SOD1 mutations. A 39-year-old woman developed muscle weakness and atrophy in the hands, which rapidly progressed and expanded to other muscles, resulting in respiratory insufficiency and death at only 10 months after the onset. Her grandmother, father and uncle had also been diagnosed as having ALS. The most noticeable neuropathological findings in the present case were marked loss of large motor neurons in the anterior horns associated with the frequent appearance of cord-like swollen, partially SOD1- and ubiquitin-immunopositive axons. These findings together with the absence of Bunina bodies are compatible with the neuropathology of FALS with SOD1 gene mutation, although Lewy body-like inclusions characteristic for this condition were not observed.
  • 走査型文字入力におけるスイッチ操作タイミング特性の測定とその自動誤り訂正への応用
    森大毅, 粕谷英樹, 森田光哉, 中野今治
    信学技報 43 - 48 2007 [Refereed][Not invited]
  • 糖尿病および多発ニューロパチーを合併した高齢発症SPG4(spastin 1726T>C)の孤発例
    福永真美, 大八木保政, 森田光哉, 重藤寛史, 谷脇考恭, 吉良潤一
    臨床神経学 359 - 361 2007 [Refereed][Not invited]
  • Takeshi Kamimura, Haruo Shimazaki, Mitsuya Morita, Imaharu Nakano, Hitoaki Okazaki, Seiji Minota
    JCR-JOURNAL OF CLINICAL RHEUMATOLOGY 12 (5) 259 - 260 1076-1608 2006/10 [Refereed][Not invited]
  • Takehisa Ishikawa, Yumi Fujio, Mitsuya Morita, Yoshihisa Takiyama, Imaharu Nakano
    Clinical Neurology 46 (7) 491 - 495 0009-918X 2006/07 [Refereed][Not invited]
     
    We report an adult case of acute cerebellitis associated with influenza A. A 25-year-old woman with fever and headache was diagnosed as having influenza A infection, because nasal swab extract was found positive in the influenza assay. She was treated with oseltamivir. After the treatment, she gradually developed gait and speech disturbance. Neurological examination revealed dysarthria with scanning slurred speech, and limb and truncal ataxia. Cerebrospinal fluid showed pleocytosis and a four-fold or greater change in the antibody titer to influenza virus A (H3N2) detected by HI. T2-weighted brain MRI demonstrated a high signal lesion in the cerebellar cortex. 123I-IMP-SPECT showed hypoperfusion in the cerebellum. Thus, acute cerebellitis associated with influenza A infection was diagnosed. Her symptoms partially improved after steroid pulse therapy, whereas the cerebellar cortical lesion observed on MRI, truncal ataxia and cerebrospinal fluid pleocytosis remained. The cerebellar cortical lesion observed on MRI disappeared 80 days after hospitalization, and the truncal ataxia and cerebrospinal fluid pleocytosis had normalized about three months later.
  • M Morita, A Al-Chalabi, PM Andersen, B Hosler, P Sapp, E Englund, JE Mitchell, JJ Habgood, J de Belleroche, J Xi, RH Brown
    NEUROLOGY 66 (6) 839 - 844 0028-3878 2006/03 [Refereed][Not invited]
     
    Objective: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD). Methods: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis. Results: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. Conclusions: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
  • A型インフルエンザ感染後に急性小脳炎を呈し、MRIにて小脳皮質病変がみとめられた1成人例
    石川剛久, 藤尾由美, 森田光哉, 瀧山嘉久, 中野今治
    臨床神経学 46 491 - 495 2006 [Refereed][Not invited]
  • 免疫グロブリン静注療法(IVIG)は機能的伝導ブロックを速やかに解消する-慢性炎症性脱髄性多発ニューロパチー(CIDP)の1例における経時的電気生理学的解析から-
    中村優子, 澤田幹雄, 嶋崎晴雄, 森田光哉, 中野今治
    神経治療学 23 (1) 57 - 61 2006 [Refereed][Not invited]
  • H Horiuchi, M Osawa, R Furutani, M Morita, W Tian, Y Awatsu, H Shimazaki, K Umetsu
    GENETIC TESTING 9 (4) 328 - 333 1090-6576 2005/12 [Refereed][Not invited]
     
    Progressive myoclonus epilepsy of the Unverricht-Lundborg type is an autosomal recessive disorder that is characterized clinically by myoclonic seizures and ataxia. The majority of affected individuals carry repeat expansions of a dodecamer in the promoter region of the cystatin B gene. The unusually high GC content of this tract is refractory to conventional polymerase chain reaction (PCR), and, as a result, a circumventive procedure involving the deamination of DNA with sodium bisulfite has been proposed. This study evaluates the effectiveness of this deamination modification for the detection of dodecamer repeat variants. An analysis of 258 healthy Japanese individuals revealed an allele with four copies of the dodecamer repeat with a frequency of 0.01, in addition to the more commonly observed two and three copy repeat alleles. Homozygous repeat expansions 600 and 680 base pairs in length were detected in the analyses of two affected individuals. For these cases, sequencing, along with an alternative PCR- stutter formation, revealed 41 and 48 copies, respectively, of the dodecamer repeat. The complete conversion of C to T was observed in the expanded tracts, indicating that no methylation occurred at the CpG sites. Based on these results, it was concluded that the use of deaminated DNA allows for a precise analysis of consecutive GC tracts.
  • 両下肢の多発性単神経根症で発症した原発不明癌による髄膜癌腫症の1剖検例
    石川剛久, 嶋崎晴雄, 森田光哉, 澤田幹雄, 瀧山嘉久, 中野今治, 川井俊郎
    臨床神経 45 32 - 37 2005 [Refereed][Not invited]
  • Takehisa Ishikawa, Haruo Shimazaki, Mitsuya Morita, Mikio Sawada, Yoshihisa Takiyama, Imaharu Nakano, Toshirou Kawai
    Clinical Neurology 45 (1) 32 - 37 0009-918X 2005/01 [Refereed][Not invited]
     
    A 54-year-old man with a history of partially dissected epidermoid cyst in the left cerebellopontine angle suffered from a slowly progressive dysesthesia and weakness in the lower extremities and trunk. Neurological examination revealed segmental muscular weakness and sensory disturbance in those regions, giving rise to the possibility of monoradiculopathy multiplex, as well as loss of tendon reflexes, dysuria and right facial nerve palsy. Electrophysiological studies indicated irregular motor axonopathy or neuronopathy and interruption of more central sensory pathways than the lumbosacral spinal nerve roots with spared peripheral sensory nerves. Although MRI demonstrated enhanced lesions in the cauda equina and lumbosacral leptomeninges, CSF cytology or a cauda equina biopsy showed no malignancy. His symptoms gradually progressed and he died 15 months after the onset. The autopsy failed to reveal any tumors in the general systemic internal organs. Histopathology demonstrated meningeal carcinomatosis with squamous-type carcinoma cells scattered in the cerebrospinal leptomeninges, and perineurium in almost all the spinal and cranial nerve roots, causing severe axonal degeneration. The dorsal root ganglions escaped tumor cell invasion. Absence of the malignant tumors in the systemic organs and the history of the operated epidermoid cyst indicate that the tumor may be the cause of the meningeal carcinomatosis in this case. Meningeal carcinomatosis almost always shows rapid progression and extremely poor prognosis with several month survival in general, and little attention has been paid that it can exhibit symptoms and signs of segmental involvement in the lumbosacral regions. Our present case prompts us to bear in mind that patients with this condition can survive fairly long, and raises the possibility that a careful neurological examination with segmental involvement will reveal such a feature more frequently than considered so far in this condition.
  • Baló病様同心円性多層性病巣を呈した多発性硬化症
    永田三保子, 松 春子, 森田光哉, 中野今治
    神経内科 61 210 - 212 2004 [Refereed][Not invited]
  • MRIで辺縁系大脳皮質に限局した造影効果を認めた単純ヘルペス脳炎の1例
    嶋崎晴雄, 稲葉利敬, 栗原秀樹, 森田光哉, 瀧山嘉久, 中野今治
    Neuro-infection 7 (1) 23 - 24 2003 [Refereed][Not invited]
  • M Morita, M Ho, BA Hosler, D McKenna-Yasek, RH Brown
    NEUROSCIENCE LETTERS 325 (1) 57 - 61 0304-3940 2002/05 [Refereed][Not invited]
     
    Hereditary spastic paraplegia (HSP) is a degenerative neuromuscular disease characterized by progressive lower extremity weakness, spasticity and hyperreflexia. Inheritance of HSP is commonly autosomal dominant, spastin was identified as the defective gene in chromosome 2p-linked autosomal dominant hereditary spastic paraplegia (AD-HSP). In a large American family with AD-HSP, we have identified a novel spastin mutation at a splice-acceptor site in intron 6 (1130-1 g --> a) and detected a corresponding aberrant transcript generated from a cryptic splice site. This is predicted to cause a frameshift and premature truncation of the abnormal spastin protein. Our data are the first to confirm that a mutation in an acceptor site in the spastin gene results in activation of a cryptic acceptor site and a translational frameshift. The clinical phenotype of this pedigree is also discussed. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • 岩津好隆, 嶋崎晴雄, 澤田幹雄, 森田光哉, 川上忠孝, 滝山嘉久, 藤本健一, 中野今治
    日本内科学会雑誌 91 (8) 242 - 244 2002 [Refereed][Not invited]
  • M Morita, M Aoki, P Sapp, D McKenna-Yasek, HR Horvitz, RH Brown
    MOLECULAR MECHANISM AND THERAPEUTICS OF AMYOTROPHIC LATERAL SCLEROSIS 1221 139 - 149 0531-5131 2001 [Refereed][Not invited]
     
    Objective: To examine the possibility that CAG/CTG expansions are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods: We have used the repeat expansion detection (RED) method to screen for CAG/CTG expansions in fifty-six cases of familial ALS (FALS), fifty-one cases of sporadic ALS (SALS) and fifty-one controls, We then tested the possibility that any detected expanded alleles originated from two specific loci, ERDA1/Dir1 or CTG18.1 using either the polymerase chain reaction (PCR) or Southern blotting. Results: CAG/CTG alleles with expansions of 144 bp or more base pairs were detected in 28.6% of FALS, 33.3% of SALS and 21.6% of controls. These alleles originated from either ERDA1/Dir1 or CTG18.1. Conclusion: The pathogenesis of familial and sporadic ALS does not commonly involve CAG/CTG expansions.
  • M Morita, K Abe, M Takahashi, Y Onodera, H Okumura, M Niino, K Tashiro, Nakano, I, Y Itoyama
    EUROPEAN JOURNAL OF NEUROLOGY 5 (4) 389 - 392 1351-5101 1998/07 [Refereed][Not invited]
     
    We have identified a novel mutation in exon 4 of the Cu/Zn superoxide dismutase (superoxide dismutase 1: SOD1) gene (GAC to GTC), which resulted in an Asp(90) to Val substitution in a Japanese family with amyotrophic lateral sclerosis (ALS) inherited as an autosomal dominant trait. The patients in this family usually died in 2-3 years without sensory or urinary impairment. The SOD1 activity was lower in the proband as compared to the normal controls. The clinical characteristics of this family resemble those of some patients heterozygous for the Asp90Ala mutation, but both the clinical features and SOD1 activity of this family differ from those of patients homozygous for the ASP90Ala mutation, Eur J Neurol 5:389-392 (C) 1998 Lippincott-Raven Publishers.
  • Y Takiyama, H Shimazaki, M Morita, M Soutome, K Sakoe, E Esumi, S Muramatsu, M Yoshida, S Igarashi, H Tanaka, S Tsuji, H Sasaki, A Wakisaka, Nakano, I, M Nishizawa
    JOURNAL OF THE NEUROLOGICAL SCIENCES 155 (2) 141 - 145 0022-510X 1998/03 [Refereed][Not invited]
     
    We studied the relationship between the number of CAG repeat units in the MJD1 gene and clinical features of Machado-Joseph disease (MJD) in eight patients from two generations of a Japanese MJD family. Because of lack of characteristic clinical signs of MJD such as dystonia, bulging eyes or facial myokymia, clinical diagnosis of MJD in this family was difficult to make prior to molecular testing for the CAG repeat expansion in the MJD1 gene. All the patients exhibited maternal transmission of MJD, and the intergenerational change in the number of CAG repeat units in the MJD1 gene was very small (+0.5+/-0.3, mean+/-S.E.M., n=4) in spite of marked genetic anticipation (-17.0 years/generation). In the present family, the degree of anticipation per repeat unit in maternal transmissions was much larger than that in maternal transmissions in the other six MJD families. This indicates that some maternal factors other than the increase of the number of CAG repeat units, which is known to be the basis of anticipation, may play a role in genetic anticipation in this MJD family. (C) 1998 Elsevier Science B.V.
  • Novel acceptor splice site mutation in the invariant AG of intron 6 of alpha-galactosidase A gene, causing Fabry disease.
    Matsumura T, Osaka H, Sugiyama N, Kawanishi C, Maruyama Y, Suzuki K, Onishi H, Yamada Y, Morita M, Aoki M, Kosaka, K
    Hum. Mutat. 11 483  1998 [Refereed][Not invited]
  • Amantadine単独投与中に服薬の中断で悪性症候群を呈した軽症Parkinson病の一例
    川上忠孝, 森田光哉, 西澤正豊, 吉田充男
    神経内科 49 356 - 360 1998 [Refereed][Not invited]
  • M Morita, M Aoki, K Abe, T Hasegawa, R Sakuma, Y Onodera, N Ichikawa, M Nishizawa, Y Itoyama
    NEUROSCIENCE LETTERS 205 (2) 79 - 82 0304-3940 1996/02 [Refereed][Not invited]
     
    We have identified a novel two-base mutation in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene (TGC to TTT), which resulted in Cys(6) to Phe substitution in a Japanese family with amyotrophic lateral sclerosis (ALS). This is the first case of familial ALS-associated two-base change of the SOD1 gene. Similar to several mutations in exon 1 of the SOD1 gene such as Ala(4) to Val, Ala(4) to Thr and Val(14) to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala(4), Cys(6) and Val(7) reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Va1(7) to Glu associates with slow progression of the disease. These findings suggest that clinical courses are variable with each mutation, even in the same exon.
  • Y SEINO, U IKEDA, H SEKIGUCHI, M MORITA, K KONISHI, T KASAHARA, K SHIMADA
    CYTOKINE 7 (3) 301 - 304 1043-4666 1995/04 [Refereed][Not invited]
     
    Cytotoxic action of leukocytes may be involved in the pathogenesis of inflammatory heart muscle disorders. We investigated the expression of rat leukocyte chemotactic cytokines-cytokine induced neutrophil chemoattractant (CINC) and JE-in cultured neonatal rat cardiac myocytes; CINC belongs to the interleukin 8 (IL-8) family and JE is a homologue of human monocyte chemoattractant protein 1 (MCP-1), In Northern blot analysis, CINC and JE transcripts were not clearly observed in unstimulated rat cardiac myocytes, However, their expression was clearly observed after exposure to tumour necrosis factor-alpha (TNF-alpha; 100 U/ml) for 26 h, We then evaluated IL-8 and MCP-I mRNA expression in human endomyocardial biopsy specimens from seven patients with idiopathic dilated cardiomyopathy by polymerase chain reaction analysis, Both IL-8 and MCP-1 mRNA transcripts were recognized in all patients studied, These results show for the first time that leukocyte chemotactic cytokines, IL-8 and MCP-1, are expressed in myocardial tissue, which might contribute to the pathogenesis of inflammatory heart muscle disorders.
  • Paraneoplastic limbic encephalitis-A case responsive to double filtration plasmapheresis and chemotherapy.
    Takeuchi Y, Doki T, Morita M, Fujimoto K, Ogawa M, Nishizawa M, Yoshida M, Muto S, Kusano E, Asano Y
    Jpn J Apheresis 14 (1) 57 - 58 1995 [Refereed][Not invited]
  • N MUKAIDA, M MORITA, Y ISHIKAWA, N RICE, S OKAMOTO, T KASAHARA, K MATSUSHIMA
    JOURNAL OF BIOLOGICAL CHEMISTRY 269 (18) 13289 - 13295 0021-9258 1994/05 [Refereed][Not invited]
     
    A glucocorticoid, dexamethasone, inhibited the production of a leukocyte chemotactic cytokine, interleukin 8 (IL-8), as well as mRNA expression by a glioblastoma cell line, T98G, stimulated with interleukin 1 (IL-1). Dexamethasone also inhibited IL-8 promoter-driven chloramphenicol acetyltransferase (CAT) activities induced by IL-1, suggesting that dexamethasone inhibited IL-8 production mainly at the transcriptional level. Moreover, CAT assay revealed that the nuclear factor-kappa B (NF-kappa B) binding site was the crucial cis-element required for conferring IL-1 responsiveness in conjunction with the CCAAT enhancer binding protein/nuclear factor-IL-6 (NF-IL6) and/or the AP-1 binding site(s). Mutation of either the AP-1 or NF-IL6 binding site did not abolish IL-8 gene repression by dexamethasone, suggesting that these sites were not targets for dexamethasone. Trimerized kappa B sequence in the IL-8 gene was enough for conferring the induction by IL-1 and inhibition by dexamethasone of CAT activity. Finally, dexamethasone diminished the IL-l-induced formation of NF-kappa B complexes, which were identified immunochemically to consist of p50 and p65, without reducing the amount of translocated factors. Collectively, dexamethasone interfered with the binding of the most essential transcription factor, NF-kappa B, to its cognate cis-element, thereby suppressing the transcription of IL-8 gene.
  • 林祐次, 池田宇一, 小川朋子, 島田和幸, 森田光哉, 吉田充男, 加藤盛人, 長谷川嗣夫
    呼吸と循環 42 379 - 382 1994 [Refereed][Not invited]
  • M MORITA, T KASAHARA, N MUKAIDA, K MATSUSHIMA, T NAGASHIMA, M NISHIZAWA, M YOSHIDA
    EUROPEAN CYTOKINE NETWORK 4 (5) 351 - 358 1148-5493 1993/09 [Refereed][Not invited]
     
    In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-g and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-la and TNF-a and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-a-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
  • Efficacy of plasma exchange and double filtration plasmapheresis on Guillain-Barre syndrome.
    Yoshida I, Ootaka S, Honma S, Takeda S, Tabei K, Asano Y, Morita M, Nishizawa M, Yoshida M
    Therapeutic Plasmapheresis 77 - 83 1993 [Refereed][Not invited]
  • 運動部医科学生の心拍数からみた日常生活の身体活動水準とVO2maxについて
    森田光哉, 宮下義啓, 二橋宏嘉, 阿部徳之助, 竹内正雄, 折本典代, 渡辺慶寿
    自治医科大学紀要 12 187 - 190 1989 [Refereed][Not invited]
  • 頻回に寛解増悪を繰り返し特異な皮膚組織所見を伴った多発性筋炎の一例
    森田光哉, 藤本健一, 吉田充男, 荒畑喜一, 杉田秀夫
    臨床神経学 29 909 - 913 1989 [Refereed][Not invited]
  • M. Morita, K. Fujimoto, M. Yoshida, K. Arahata, H. Sugita
    Clinical Neurology 29 (7) 909 - 913 0009-918X 1989 [Refereed][Not invited]

Books etc

  • 指定難病ペディア2019
    (Contributor27原発性側索硬化症)
    日本医師会 2019/06
  • 水澤, 英洋 (Contributor13. 原発性側索硬化症)
    南江堂 2018/05 9784524256174 xiii, 392p
  • 青木, 正志 (Contributor6 ALSは単一疾患ですか,どのような亜型が存在しますか?(予後を含む))
    中外医学社 2017/10 9784498228887 iv, 352p
  • 平田, 幸一 (Contributor変性疾患)
    中外医学社 2016/02 9784498075962 iii, 362p
  • 別冊 日本臨床 新領域別症候群シリーズ No.27 神経症候群(第2版)(II)
    秋本千鶴, 森田光哉 (ContributorALS9(angiogenin:ANG))
    日本臨床社 2014/03
  • 飯森, 眞喜雄, 内山, 真一郎, 片山, 容一, 岸本, 年史, 水澤, 英洋, 北川, 泰久, 寺本, 明, 三村, 將 (Contributor筋萎縮性側索硬化症)
    日本医師会,南山堂 (発売) 2013/11 9784525248314 362p
  • 症例を診て問題を解いて学ぶ 自治医科大学内科研修トレーニング
    川西康太郎, 森田光哉 (ContributorV 神経内科 Case 5 歩行障害を主訴に入院した59歳の女性)
    メジカルビュー社 2013/10
  • すべてがわかるALS・運動ニューロン疾患
    森田 光哉 (ContributorSOD1)
    2013/06
  • 今日の神経疾患治療指針 第2版
    森田 光哉 (Contributor筋萎縮性側索硬化症)
    医学書院 2013/03
  • 脊髄性筋萎縮症診療マニュアル
    森田 光哉 (Contributor遺伝子疾患としてのSMA -成人発症SMAの原因と病態は何ですか-)
    金芳堂 2012/05
  • ALSマニュアル決定版!
    森田 光哉 (Contributor呼吸補助療法)
    日本プランニングセンター 2008
  • New専門医を目指すケース・メソッド・アプローチ6神経疾患
    森田光哉, 中野今治 (ContributorCASE 23 下肢の痙性麻痺にて発症し、四肢麻痺に進展した43歳男性)
    日本医事新報社 2008
  • 運動器リハビリテーション実践マニュアル
    森田 光哉 (Contributorポストポリオ症候群)
    全日本出版協会 2008
  • 神経難病のすべて
    森田光哉, 中野今治 (Contributor最新の在宅コミュニケーション機器)
    新興医学出版社 2007
  • EBM神経疾患の治療2007-2008
    森田光哉, 中野今治 (Contributor運動ニューロン疾患 本邦と米国でのガイドラインはどこが違うか)
    中外医学社 2007/01
  • 神経疾患 最新の治療2006-2008
    森田光哉, 中野今治 (Contributor筋萎縮性側索硬化症(ALS)・運動ニューロン疾患)
    南江堂 2006/03
  • これだけは知っておきたい臨床医の画像診断
    森田光哉, 中野今治 (Contributor筋萎縮性側索硬化症)
    中外医学者 2003/06
  • Familial Amyotrophic Lateral Sclerosis: A Review
    ()
    Neuromuscular Diseases: From Basic Mechanisms to Clinical Management 2000
  • Genetics of amyotrophic lateral sclerosis : an overview.(共著)
    ()
    Amyotrophic Lateral Sclerosis. London : Martin Dunitz 1999

Conference Activities & Talks

  • Molecular mechanism of interleukin8(IL-8)gene repression by a glucocorticoid.(共著)  [Not invited]
    Combined Meeting 8th Intl' Lymphok. 4th Intl' Cytokine Workshop.  1993
  • Molecular mechanism of IL-8 gene repression by a glucocorticoid and FK506.(共著)  [Not invited]
    Joint Meeting of AAI and Clin. Immunol. Society.  1993

MISC

  • 多施設共同前向きコホートでみたALS患者の背景と予後因子の検討
    林 直毅, 熱田 直樹, 横井 大知, 中村 亮一, 勝野 雅央, 和泉 唯信, 金井 数明, 服部 信孝, 谷口 彰, 森田 光哉, 狩野 修, 澁谷 和幹, 桑原 聡, 鈴木 直輝, 青木 正志, 餐場 育子, 溝口 功一, 梶 龍兒, 祖父江 元, JaCALS  臨床神経学  59-  (Suppl.)  S359  -S359  2019/11  [Not refereed][Not invited]
  • 急性期脳卒中患者の前頭前野ニューロフィードバック訓練効果差
    手塚正幸, 松本万由子, 櫻田武, 中嶋剛, 森田光哉, 川合謙介  第33回 日本ニューロモデュレーション学会  2019/05  [Not refereed][Not invited]
  • 急性期脳卒中患者のワーキングメモリ機能個人差とfNIRSによる前頭前野ニューロフィードバック訓練効果
    手塚正幸, 松本万由子, 櫻田武, 中嶋剛, 森田光哉, 川合謙介  第44回 日本脳卒中学会学術集会  2019/03  [Not refereed][Not invited]
  • ALSFRS-Rを用いた筋萎縮性側索硬化症患者の進行、予後予測と治験デザイン
    熱田 直樹, 中村 亮一, 林 直毅, 横井 大知, 伊藤 瑞規, 渡辺 宏久, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 阿部 康二, 狩野 修, 桑原 聡, 青木 正志, 金井 数明, 服部 信孝, 梶 龍兒, 祖父江 元, JaCALS  臨床神経学  58-  (Suppl.)  S205  -S205  2018/12  [Not refereed][Not invited]
  • 運動中のワーキングメモリ機能差に依存したニューロフィードバック訓練効果
    松本万由子, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 平井真洋, 藤本茂, 川合謙介, 山本紳一郎  第12回 Motor Control研究会  2018/08  [Not refereed][Not invited]
  • テイラーメード・ニューロフィードバック系構築に向けた運動学習中のワーキングメモリの個人差を反映する神経基盤の同定
    松本万由子, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 平井真洋, 山本紳一郎, 藤本茂, 川合謙介  第41回 日本神経科学大会  2018/07  [Not refereed][Not invited]
  • Genki Tohnai, Ryoichi Nakamura, Jun Sone, Masahiro Nakatochi, Daichi Yokoi, Masahisa Katsuno, Hazuki Watanabe, Hirohisa Watanabe, Mizuki Ito, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Masashi Aoki, Nobutaka Hattori, Osamu Onodera, Hiroya Naruse, Jun Mitsui, Yuji Takahashi, Jun Goto, Hiroyuki Ishiura, Shinichi Morishita, Jun Yoshimura, Koichiro Doi, Shoji Tsuji, Kenji Nakashima, Ryuji Kaji, Naoki Atsuta, Gen Sobue  Neurobiology of aging  64-  (158)  158.e15-158.e19  2018/04  [Refereed][Not invited]
     
    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67-62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.
  • 運動学習中の最適注意戦略個人差に関する健常者・脳卒中患者の共通神経基盤
    櫻田武, 後藤彩, 手塚正幸, 中嶋剛, 森田光哉, 山本紳一郎, 平井真洋, 川合謙介  第20回日本光脳機能イメージング学会  2017/07  [Not refereed][Not invited]
  • 運動学習中における最適な注意の向け方を決定する前頭前野活動個人差
    後藤彩, 櫻田武, 手塚正幸, 中嶋剛, 森田光哉, 山本紳一郎, 平井真洋, 川合謙介  第40回 日本神経科学大会  2017/07  [Not refereed][Not invited]
  • 運動機能障害リハビリテーションにおけるニューロモジュレーションのための認知-運動機能連関に関する個人差とその神経基盤
    櫻田武, 後藤彩, 中嶋剛, 平井真洋, 森田光哉, 山本紳一郎, 渡辺英寿, 川合謙介  第56回 日本定位・機能神経外科学会  2017/01  [Not refereed][Not invited]
  • Hazuki Watanabe, Naoki Atsuta, Akihiro Hirakawa, Ryoichi Nakamura, Masahiro Nakatochi, Shinsuke Ishigaki, Aritoshi Iida, Shiro Ikegawa, Michiaki Kubo, Daichi Yokoi, Hirohisa Watanabe, Mizuki Ito, Masahisa Katsuno, Yuishin Izumi, Mitsuya Morita, Kazuaki Kanai, Akira Taniguchi, Ikuko Aiba, Koji Abe, Koichi Mizoguchi, Masaya Oda, Osamu Kano, Koichi Okamoto, Satoshi Kuwabara, Kazuko Hasegawa, Takashi Imai, Akihiro Kawata, Masashi Aoki, Shoji Tsuji, Kenji Nakashima, Ryuji Kaji, Gen Sobue  Journal of Neurology, Neurosurgery and Psychiatry  87-  (8)  851  -858  2016/01  [Refereed][Not invited]
     
    Objective: To classify the patterns of functional decline in patients with sporadic amyotrophic lateral sclerosis (ALS) and explore the genetic backgrounds that modified these patterns. Methods: We included 465 patients with sporadic ALS in the analysis and clustered the longitudinal functional scores in the registered patients, using a mixture approach of a non-linear mixed-effects model. We conducted a genome-wide analysis of 572 983 single nucleotide polymorphisms (SNPs). We then assessed the association between the clusters of longitudinal functional scores and SNPs. Results: We identified the following four clusters of longitudinal functional decline in the cases: a rapid decline cluster, an intermediate decline cluster, a sigmoidal decline cluster and a moderate decline cluster. We identified seven SNPs associated with the rapid decline cluster, using a recessive model (p=3.47-8.34×10-8). The OR for the probabilities of the rapid decline cluster ranged from 5.5 to 5.84. Homozygosity for the minor alleles in the seven SNPs, which constituted a linkage disequilibrium (LD) block, was associated with decreased expression of TTN (encoding Titin, a large sarcomere protein) in the expression quantitative trait loci database of a large-scale Japanese genetic variation database (p=8.6×10-10-1.1×10-7). TTN expression in immortalised lymphocyte lines was decreased in patients who were homozygous for the minor alleles compared with those who were homozygous for the major alleles (n=19 in each group, p=0.002). Conclusions: We detected an LD block associated with a rapid functional decline in patients with sporadic ALS, which is linked to decreased expression of TTN.
  • Akihiko Miyauchi, Yukifumi Monden, Meri Watanabe, Hideo Sugie, Mitsuya Morita, Takeshi Kezuka, Mariko Momoi, Takanori Yamagata  NEUROPEDIATRICS  45-  (3)  E2  -E2  2014/06  [Not refereed][Not invited]
  • 中野今治, 益子貴史, 手塚修一, 秋本千鶴, 森田光哉, 斎藤加代子, 樋口雄二郎, 橋口昭大, 高嶋博  神経変性疾患に関する調査研究 平成25年度 総括・分担研究報告書  207  -209  2014  [Not refereed][Not invited]
  • ALS患者の症状進行パターン 多施設共同ALSコホートの解析から
    渡辺 はづき, 熱田 直樹, 中村 亮一, 平川 晃弘, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 和泉 唯信, 梶 龍兒, 森田 光哉, 大垣 光太郎, 谷口 彰, 溝口 功一, 岡本 幸市, 長谷川 一子, 青木 正志, 中野 今治, 祖父江 元  臨床神経学  53-  (12)  1442  -1442  2013/12  [Not refereed][Not invited]
  • 浦野義章, 荻野美恵子, RABKIN Judith, 熱田直樹, 村松剛, 立石貴久, 森田光哉, 今井尚志, 藤村晴俊, 吉良潤一, 中野今治, 祖父江元, 三本博, 西山和利  日本神経学会学術大会プログラム・抄録集  54th-  (12)  517  -1622  2013/12  [Not refereed][Not invited]
  • 傍腫瘍性小脳変性症(PCD)の新規抗原(brain-type creatine kinase;CKB)の同定
    手塚 修一, 黒岩 憲二, 滑川 道人, 森田 光哉, 冨永 薫, 田中 惠子, 瀧山 嘉久, 遠藤 仁司, 中野 今治  臨床神経学  53-  (12)  1541  -1541  2013/12  [Not refereed][Not invited]
  • Syuichi Tetsuka, Kaoru Tominaga, Kenji Kuroiwa, Mitsuya Morita, Hitoshi Endo  ANNALS OF NEUROLOGY  74-  S87  -S87  2013/10  [Not refereed][Not invited]
  • 手塚修一, 黒岩憲二, 滑川道人, 森田光哉, 冨永薫, 田中惠子, 瀧山嘉久, 遠藤仁司, 中野今治  日本神経学会学術大会プログラム・抄録集  54th-  430  2013  [Not refereed][Not invited]
  • 中野今治, 手塚修一, 森田光哉, 飯田有俊, 上原里程, 池川志郎  神経変性疾患に関する調査研究 平成24年度 総括・分担研究報告書  237  -240  2013  [Not refereed][Not invited]
  • 中野今治, 益子貴史, 手塚修一, 秋本千鶴, 森田光哉, 橋口昭大, 高嶋博, 相楽有規子, 斎藤加代子  脊髄性筋萎縮症の臨床実態の分析、遺伝子解析、治療法開発の研究 平成24年度 総括・分担研究報告書  21  -24  2013  [Not refereed][Not invited]
  • 中野今治, 益子貴史, 手塚修一, 秋本千鶴, 森田光哉, 橋口昭大, 高嶋博, 相楽有規子, 斎藤加代子  脊髄性筋萎縮症の臨床実態の分析、遺伝子解析、治療法開発の研究 平成22-24年度 総合研究報告書  35  -37  2013  [Not refereed][Not invited]
  • 筋萎縮性側索硬化症(ALS)・ハンチントン病(HD)の認知機能
    安藤喜仁, 森田光哉, 中野今治  Modern Physician  33-  (1)  95  -98  2013  [Not refereed][Invited]
  • 多施設共同ALS患者コホートにおける上位運動ニューロン症候を呈さない例の臨床像
    熱田 直樹, 中村 亮一, 渡辺 はづき, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 田中 章景, 梶 龍兒, 森田 光哉, 和泉 唯信, 青木 正志, 溝口 功一, 谷口 彰, 岡本 幸市, 饗場 郁子, 川田 明広, 長谷川 一子, 大垣 光太郎, 中野 今治, 祖父江 元  臨床神経学  52-  (12)  1483  -1483  2012/12  [Not refereed][Not invited]
  • 我が国のALS患者に対する換気補助療法の現状と予後 JaCALSの解析から
    渡辺 はづき, 熱田 直樹, 中村 亮一, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 田中 章景, 梶 龍兒, 和泉 唯信, 森田 光哉, 青木 正志, 溝口 功一, 谷口 彰, 岡本 幸市, 饗場 郁子, 川田 明広, 長谷川 一子, 大垣 光太郎, 中野 今治, 祖父江 元  臨床神経学  52-  (12)  1605  -1605  2012/12  [Not refereed][Not invited]
  • 筋萎縮性側索硬化症とその他の運動ニューロン疾患
    森田光哉, 中野今治  医薬ジャーナル  48-  (5)  1281  -1285  2012/05  [Not refereed][Invited]
  • Mitsuya Morita, Imaharu Nakano  ANNALS OF NEUROLOGY  72-  S23  -S24  2012  [Not refereed][Not invited]
  • 中野今治, 益子貴史, 手塚修一, 秋本千鶴, 森田光哉, 相楽有規子, 斎藤加代子  神経変性疾患に関する調査研究 平成23年度 総括・分担研究報告書  134  -136  2012  [Not refereed][Not invited]
  • 中野今治, 益子貴史, 手塚修一, 秋本千鶴, 森田光哉, 相楽有規子, 斎藤加代子  脊髄性筋萎縮症の臨床実態の分析、遺伝子解析、治療法開発の研究 平成23年度 総括・分担研究報告書  16  -18  2012  [Not refereed][Not invited]
  • 成人型脊髄性筋萎縮症SMAの診断基準症例の臨床と遺伝学的背景
    益子貴史, 森田光哉, 中野今治  難病と在宅ケア  18-  (4)  56  -58  2012  [Not refereed][Invited]
  • ALS9 (Angiogenin; ANG)
    秋本千鶴, 森田光哉, 中野今治  神経内科  76-  (5)  483  -488  2012  [Not refereed][Invited]
  • 川西康太郎, 森田光哉, 直井為任, 亀田知明, 林夢夏, 中村優子, 滑川道人, 嶋崎晴雄, 川上忠孝, 池口邦彦, 藤本健一, 中野今治  Neuroinfection  16-  (2)  193  2011/10  [Not refereed][Not invited]
  • Magdalena Kuzma-Kozakiewicz, Mariusz Berdynski, Anna Lusakowska, Mitsuya Morita, Cezary Zekanowski, Hubert Kwiecinski  NEUROLOGY  76-  (9)  A411  -A411  2011/03  [Not refereed][Not invited]
  • Chizuru Akimoto, Mitsuya Morita, Imaharu Nakano  NEUROLOGY  76-  (9)  A585  -A585  2011/03  [Not refereed][Not invited]
  • 滑川道人, 嶋崎晴雄, 森田光哉, 川上忠孝, 村松慎一, 池口邦彦, 藤本健一, 中野今治  日本内科学会雑誌  100-  235  2011/02  [Not refereed][Not invited]
  • 中野今治, 手塚修一, 秋本千鶴, 森田光哉  脊髄性筋萎縮症の臨床実態の分析、遺伝子解析、治療法開発の研究 平成22年度 総括・分担研究報告書  14  -16  2011  [Not refereed][Not invited]
  • 滑川道人, 嶋崎晴雄, 森田光哉, 川上忠孝, 村松慎一, 池口邦彦, 藤本健一, 中野今治  日本内科学会雑誌  99-  155  2010/02  [Not refereed][Not invited]
  • ALS患者の前向き縦断像把握システム(JaCALS)による予後予測
    熱田 直樹, 渡辺 宏久, 伊藤 瑞規, 千田 譲, 中野 今治, 森田 光哉, 青木 正志, 湯浅 龍彦, 辻 省次, 梶 龍兒  臨床神経学  49-  (12)  1030  -1030  2009/12  [Not refereed][Not invited]
  • C. Akimoto, M. Morita, I. Nakano  JOURNAL OF THE NEUROLOGICAL SCIENCES  285-  S266  -S266  2009/10  [Not refereed][Not invited]
  • Chizuru Akimoto, Mitsuya Morita, Imaharu Nakano  NEUROLOGY  72-  (11)  A391  -A391  2009/03  [Not refereed][Not invited]
  • 直井為任, 滑川道人, 浅利さやか, 中村優子, 手塚修一, 澤田幹雄, 嶋崎晴雄, 森田光哉, 川上忠孝, 池口邦彦, 藤本健一, 中野今治  日本神経学会総会プログラム・抄録集  50th-  276  2009  [Not refereed][Not invited]
  • 滑川道人, 手塚修一, 浅利さやか, 清水綾子, 河又千鶴, 嶋崎晴雄, 森田光哉, 川上忠孝, 藤本健一, 中野今治  日本内科学会雑誌  97-  170  2008/02  [Not refereed][Not invited]
  • 痙性対麻痺、HAM
    森田 光哉  モダンフィジシャン  28-  (5)  680  -683  2008  [Not refereed][Invited]
  • Takehisa Ishikawa, Mitsuya Morita, Imaharu Nakano  Brain and Nerve  59-  (10)  1093  -1098  2007/10  [Not refereed][Not invited]
     
    Single photon emission computed tomography (SPECT) studies have been applied for evaluation of regional cerebral blood flow (rCBF) in various neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALS-D). Brain perfusion SPECT using statistical image analysis is useful for accurate and objective diagnosis to evaluate slight decreases in rCBF, even in cases difficult to assess by visual inspection. We have used statistical parametric mapping (SPM), three-dimensional stereotactic surface projection (3D-SSP), easy Z-score imaging system (eZIS) as statistical image analyses. ALS-D cases, even if a case manifests minimal mentality change, showed obvious rCBF reduction in the bilateral prefrontal area with some irregularity and laterality of its decrease. This abnormality was clear in ALS-D compared with classic ALS. Our study has demonstrated that brain perfusion SPECT imaging using statistical image analyses is quite useful as an adjunct to presume the existence of dementia in ALS, even if ALS patients have trouble in verbal or manual communication of the language because of progressive bulbar symptoms and muscle weakness. Thus, for ALS patients with any subtle signs and symptoms suggesting dementia, we recommend a SPECT study with use of statistical image analyses.
  • 浅利さやか, 滑川道人, 清水綾子, 中村優子, 森田光哉, 藤本健一, 中野今治  日本神経救急学会雑誌  20-  (1)  29  2007/06  [Not refereed][Not invited]
  • 最新の在宅コミュニケーション機器
    森田光哉, 中野今治  神経難病のすべて  307  -310  2007  [Not refereed][Not invited]
  • 認知症を伴うALS の脳血流画像
    石川剛久, 森田光哉, 中野今治  BARAIN and NERVE  59-  1093  -1098  2007  [Not refereed][Invited]
  • 運動ニューロン疾患 本邦と米国でのガイドラインはどこが違うか
    森田光哉, 中野今治  EBM神経疾患の治療  248  -250  2006  [Not refereed][Not invited]
  • ALS患者さんにおける呼吸補助療法
    森田光哉  難病と在宅ケア  12-  (6)  29  -32  2006  [Not refereed][Not invited]
  • 筋萎縮性側索硬化症(ALS)・運動ニューロン疾患
    森田光哉, 中野今治  神経疾患 最新の治療2006-2008  187  -189  2006  [Not refereed][Not invited]
  • T Ishikawa, M Morita, Nakano, I  JOURNAL OF THE NEUROLOGICAL SCIENCES  238-  S209  -S209  2005/11  [Not refereed][Not invited]
  • 石川 剛久, 嶋崎 晴雄, 森田 光哉, 澤田 幹雄, 瀧山 嘉久, 中野 今治, 川井 俊郎, 斉藤 建  Neuropathology : official journal the Japanese Society of Neuropathology  23-  66  -66  2003/05
  • 筋萎縮性側索硬化症.これだけは知っておきたい臨床医の画像診断
    臨床医  29巻(増刊号)、790-791-  2003  [Not refereed][Not invited]
  • Brachial amyotrophic diplegia.(共著)
    医学のあゆみ  205(2), p124-126-  2003  [Not refereed][Not invited]
  • 森田光哉, 中野今治  総合リハビリテーション  25-  (10)  1157  -1162  1997  [Not refereed][Invited]
  • IL-1β変換酵素欠損マウスを用いたIL-1β産生機構の解析
    森田光哉, 笠原忠  臨床免疫  28-  (10)  108  -112  1996  [Not refereed][Invited]
  • IL-1(インターロイキン-1)(共著)
    medicina94  31-  (11)  678  -679  1994  [Not refereed][Not invited]
  • インターロイキン8(共著)
    BIOmedica  8-  (9)  42  -45  1993  [Not refereed][Not invited]

Research Grants & Projects

  • 運動ニューロン疾患における遺伝学
    遺伝子科学研究
  • Genetics in motor neuron disease
    Gene Science Research


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