Updated on 2025/08/22

写真a

 
HISAHARA Shin
 
Organization
School of Medicine Department of Neurology Professor
Title
Professor
External link

Degree

  • 医学博士

Research Interests

  • オリゴデンドロサイト

  • 実験的自己免疫性脳脊髄炎

  • 神経幹細胞

  • 初代培養

  • 多発性硬化症

  • SIRTファミリー

  • 細胞骨格タンパク

  • 幹細胞分化

  • 幹細胞増殖

  • 臨床神経学(神経内科学) 分子神経生物学

  • 分子神経生物学

  • アポトーシス

  • caspaseファミリー

Research Areas

  • Life Science / Neuroscience-general

  • Life Science / Molecular biology

  • Life Science / Neurology

Education

  • University of Tsukuba

    - 1999.3

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  • School of Medicine, Sapporo Medical University

    - 1991.3

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    Country: Japan

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Professional Memberships

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Papers

  • 小脳性運動失調を主徴とした抗contactin-1(CNTN1)抗体陽性nodopathyの一例

    河田 由香, 池田 和奈, 種本 真将, 横川 和樹, 山田 稔, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 緒方 英紀, 磯部 紀子, 久原 真

    臨床神経学   63 ( 11 )   778 - 778   2023.11

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  • 小脳性運動失調を主徴とした抗contactin-1(CNTN1)抗体陽性nodopathyの一例

    河田 由香, 池田 和奈, 種本 真将, 横川 和樹, 山田 稔, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 緒方 英紀, 磯部 紀子, 久原 真

    臨床神経学   63 ( 11 )   778 - 778   2023.11

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  • 神経筋疾患の問題症例 亜急性に進行した小脳性運動失調症と脱髄性ニューロパチーの一例

    河田 由香, 池田 和奈, 山田 稔, 齋藤 太郎, 津田 玲子, 鈴木 秀一郎, 緒方 英紀, 磯部 紀子, 久原 真

    臨床神経生理学   51 ( 5 )   508 - 508   2023.10

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    Language:Japanese   Publisher:(一社)日本臨床神経生理学会  

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  • 発症早期の自己免疫性てんかんの臨床的特徴の検討

    種本 真将, 横川 和樹, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 山本 彬広, 外山 祐一郎, 古山 裕康, 溝渕 雅広, 佐光 一也, 久原 真

    臨床神経学   63 ( Suppl. )   S321 - S321   2023.9

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  • 高齢発症の抗GluR抗体陽性脳炎にリツキシマブ療法が効果を示した1例

    種本 真将, 山本 彬広, 河田 由香, 横川 和樹, 山田 稔, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 高橋 幸利, 久原 真

    臨床神経学   63 ( 5 )   325 - 325   2023.5

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  • クリーゼ中に胸腺摘除術を施行し良好な転帰が得られた胸腺腫合併抗AChR抗体陽性全身型重症筋無力症の一例

    河田 由香, 種本 真将, 山田 稔, 横川 和樹, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 久原 真, 高瀬 貴章, 宮島 正博, 渡辺 敦

    臨床神経学   63 ( 5 )   325 - 325   2023.5

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  • クリーゼ中に胸腺摘除術を施行し良好な転帰が得られた胸腺腫合併抗AChR抗体陽性全身型重症筋無力症の一例

    河田 由香, 種本 真将, 山田 稔, 横川 和樹, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 久原 真, 高瀬 貴章, 宮島 正博, 渡辺 敦

    臨床神経学   63 ( 5 )   325 - 325   2023.5

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  • Transthyretin Variant Amyloidosis with a TTR A97D (p.A117D) Mutation Manifesting Remarkable Asymmetric Neuropathy

    Kazuna Ikeda, Daisuke Yamamoto, Keiko Usui, Hiroki Takeuchi, Nobuyuki Oka, Nagaaki Katoh, Masahide Yazaki, Fuyuki Kametani, Ichizo Nishino, Shin Hisahara

    Internal Medicine   2023

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

    DOI: 10.2169/internalmedicine.0798-22

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  • Anti-signal Recognition Particle Antibody-positive Immune-mediated Myopathy after mRNA-1273 SARS-CoV-2 Vaccination.

    Masanobu Tanemoto, Ryosuke Oda, Yuichiro Toyama, Hirohiko Shizukawa, Kazuki Yokokawa, Taro Saito, Syuuichirou Suzuki, Akihiro Matsumura, Shin Hisahara

    Internal medicine (Tokyo, Japan)   61 ( 23 )   3605 - 3609   2022.12

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    A 26-year-old Japanese woman developed a fever, myalgia and gait disturbance one day after receiving the second dose of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. A neurological examination revealed symmetrical weakness and myalgia in proximal lower limbs, and a blood examination showed prominent elevation of creatinine kinase. Magnetic resonance imaging (MRI) revealed a high signal intensity in the thigh muscles on short-tau inversion recovery images, and antibody testing revealed positive findings for anti-signal recognition particle (SRP) antibody. Thus, anti-SRP antibody-positive immune-mediated myopathy was diagnosed. We initiated immunotherapy, and she was ultimately able to walk stably.

    DOI: 10.2169/internalmedicine.0404-22

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  • 脱髄性ニューロパチーを認めたサルコイドーシスの1例

    河田 由香, 種本 真将, 山田 稔, 横川 和樹, 齋藤 太郎, 岩原 直敏, 松村 晃寛, 鈴木 秀一郎, 久原 真, 松浦 洋介

    臨床神経学   62 ( 12 )   975 - 975   2022.12

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  • てんかん発作で発症した自己免疫性神経疾患8症例の検討

    種本 真将, 横川 和樹, 齋藤 太郎, 松村 晃寛, 鈴木 秀一郎, 久原 真

    臨床神経学   62 ( 12 )   978 - 978   2022.12

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  • mRNA-1273 SARS-CoV-2ワクチン接種後に発症した抗SRP抗体陽性ミオパチーの1例

    種本 真将, 鈴木 秀一郎, 松村 晃寛, 横川 和樹, 久原 真, 静川 裕彦

    神経治療学   39 ( 6 )   S263 - S263   2022.10

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  • 脳神経内科外来のパーキンソン病患者における便秘の有訴者数と臨床像

    鈴木 秀一郎, 河田 由香, 種本 真将, 池田 和奈, 横川 和樹, 松村 晃寛, 久原 真

    神経治療学   39 ( 6 )   S288 - S288   2022.10

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  • Activation of SIRT1 promotes membrane resealing via cortactin

    Naotoshi Iwahara, Kuya Azekami, Ryusuke Hosoda, Iyori Nojima, Shin Hisahara, Atsushi Kuno

    Scientific Reports   12 ( 1 )   2022.9

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

    Abstract

    Muscular dystrophies are inherited myopathic disorders characterized by progressive muscle weakness. Recently, several gene therapies have been developed; however, the treatment options are still limited. Resveratrol, an activator of SIRT1, ameliorates muscular function in muscular dystrophy patients and dystrophin-deficient mdx mice, although its mechanism is still not fully elucidated. Here, we investigated the effects of resveratrol on membrane resealing. We found that resveratrol promoted membrane repair in C2C12 cells via the activation of SIRT1. To elucidate the mechanism by which resveratrol promotes membrane resealing, we focused on the reorganization of the cytoskeleton, which occurs in the early phase of membrane repair. Treatment with resveratrol promoted actin accumulation at the injured site. We also examined the role of cortactin in membrane resealing. Cortactin accumulated at the injury site, and cortactin knockdown suppressed membrane resealing and reorganization of the cytoskeleton. Additionally, SIRT1 deacetylated cortactin and promoted the interaction between cortactin and F-actin, thus possibly enhancing the accumulation of cortactin at the injury site. Finally, we performed a membrane repair assay using single fiber myotubes from control and resveratrol-fed mice, where the oral treatment with resveratrol promoted membrane repair ex vivo. These findings suggest that resveratrol promotes membrane repair via the SIRT1/cortactin axis.

    Other Link: https://www.nature.com/articles/s41598-022-19136-1

    DOI: 10.1038/s41598-022-19136-1

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  • Ubiquitin-dependent rapid degradation conceals a cell-protective function of cytoplasmic SIRT3 against oxidative stress

    Takashi Hayashi, Takashi Matsushita, Shin Hisahara, Naotoshi Iwahara, Atsushi Kuno, Risa Kunimoto, Ryusuke Hosoda, Masaya Tanno, Shun Shimohama, Yoshiyuki Horio

    The Journal of Biochemistry   171 ( 2 )   201 - 213   2022.2

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

    Abstract

    SIRT3 is an NAD+-dependent protein deacetylase localized in mitochondria. Several studies reported localization of SIRT3 in the cytoplasm or nucleus, but data of these studies were not consistent. We detected expression of mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs in the mouse brain, and we also found SIRT3 immunostaining of mitochondria and cytoplasm in the brain and cultured neural cells. However, expression levels of SIRT3ct in COS cells transfected with SIRT3ct cDNA were much lower than those of SIRT3mt. We found that SIRT3ct but not SIRT3mt was promptly degraded by ubiquitin-dependent degradation, in which SIRT3ct degradation was mediated mainly by ubiquitination of NH2-terminal methionine and partly by that of lysine residues of SIRT3ct. SIRT3ct expression level was significantly enhanced by the treatment of cells with staurosporine or H2O2. H2O2 treatment promoted nuclear translocation of SIRT3ct and induced histone H3 deacetylation and superoxide dismutase 2 expression. Overexpression of SIRT3ct decreased cell death caused by H2O2 at levels similar to those achieved by overexpression of SIRT3mt. Knockdown of Sirt3 mRNA increased cell death caused by amyloid-β (Aβ), and overexpression of SIRT3ct suppressed the toxic function of Aβ in PC12 cells. These results indicate that SIRT3ct promotes cell survival under physiological and pathological conditions.

    Other Link: https://academic.oup.com/jb/article-pdf/171/2/201/42644412/mvab119.pdf

    DOI: 10.1093/jb/mvab119

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  • Abrupt Onset of Cardiac Tamponade in Sarcoidosis.

    Toshiyuki Yano, Shin Hisahara, Nobutaka Nagano, Takahiro Noto, Toshifumi Ogawa, Ryo Nishikawa, Masayuki Koyama, Hidemichi Kouzu, Atsuko Muranaka, Akiyoshi Hashimoto, Shun Shimohama, Tetsuji Miura

    International heart journal   62 ( 5 )   1176 - 1181   2021.9

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    DOI: 10.1536/ihj.21-167

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  • 臨床病型が大きく異なりFUS遺伝子変異のmosaicismが示唆された家族性ALS母子例

    久原 真, 西山 亜由美, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 石川 亜貴, 櫻井 晃洋, 元池 育子, 青木 正志, 青木 洋子, 下濱 俊

    臨床神経学   61 ( Suppl. )   S293 - S293   2021.9

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  • Sporadic Amyotrophic Lateral Sclerosis Due to a FUS P525L Mutation with Asymmetric Muscle Weakness and Anti-ganglioside Antibodies.

    Masanobu Tanemoto, Shin Hisahara, Kazuna Ikeda, Kazuki Yokokawa, Tatsuo Manabe, Reiko Tsuda, Daisuke Yamamoto, Takashi Matsushita, Akihiro Matsumura, Syuuichirou Suzuki, Shun Shimohama

    Internal medicine (Tokyo, Japan)   60 ( 12 )   1949 - 1953   2021.6

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    Amyotrophic lateral sclerosis (ALS) due to a fused in sarcoma (FUS) P525L mutation is characterized by a rapidly progressive course. Multifocal motor neuropathy (MMN) may resemble ALS in early stage and is associated with anti-ganglioside antibodies. A 38-year-old woman was admitted to our hospital because of progressive muscle weakness in the right limbs. She had mild mental retardation and minor deformities. Initially, we suspected MMN given the asymmetric muscle weakness and detection of anti-ganglioside antibodies. However, physical and electrophysiological tests did not support MMN, instead suggesting ALS. We confirmed a heterozygous P525L mutation and finally diagnosed this case as ALS due to an FUS mutation.

    DOI: 10.2169/internalmedicine.6168-20

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  • SIRT1 decelerates morphological processing of oligodendrocyte cell lines and regulates the expression of cytoskeleton-related oligodendrocyte proteins. International journal

    Shin Hisahara, Naotoshi Iwahara, Takashi Matsushita, Syuuichirou Suzuki, Akihiro Matsumura, Mai Fujikura, Kazuki Yokokawa, Taro Saito, Tatsuo Manabe, Jun Kawamata, Yoshiyuki Horio, Shun Shimohama

    Biochemical and biophysical research communications   546   7 - 14   2021.3

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    SIRT1 is involved in the regulation of a variety of biological processes such as metabolism, stress response, autophagy and differentiation. Although progenitor cells of oligodendrocytes (OPCs) express high level of SIRT1, its function on differentiation is unknown. Because we have shown that SIRT1 plays a pivotal role in differentiation of neural precursor cells, we hypothesized that SIRT1 may also participate in the differentiation of oligodendrocytes (OLGs). We examined whether SIRT1 was expressed in two human oligodendrocyte cell lines: KG-1-C and MO 3.13 OLG. Transfection of cell lines with SIRT1-siRNA and SIRT2-siRNA promoted the extension of cellular processes. SIRT1-siRNA and SIRT2-siRNA increased acetyl-α-tubulin level, conversely, over expression of SIRTs resulted in decreased the ratio of acetyl-α-tubulin to α-tubulin. We also found knockdown of SIRT1 and SIRT2 induced overexpression of βIV-tubulin and tubulin polymerization promoting protein (TPPP) (OLG-specific cytoskeleton-related molecules) that distributed widely in cell bodies. Taken together, SIRT1 may play a role in oligodenroglial differentiation and myelinogenesis.

    DOI: 10.1016/j.bbrc.2021.01.095

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  • Possible Somatic Mosaicism of Novel FUS Variant in Familial Amyotrophic Lateral Sclerosis. International journal

    Shin Hisahara, Ayumi Nishiyama, Emiko Tsuda, Syuuichirou Suzuki, Akihiro Matsumura, Aki Ishikawa, Akihiro Sakurai, Ikuko N Motoike, Masashi Aoki, Yoko Aoki, Shun Shimohama

    Neurology. Genetics   7 ( 1 )   e552   2021.2

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    DOI: 10.1212/NXG.0000000000000552

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  • 非典型的な臨床型のFUS遺伝子変異による孤発性と考えられるALSの1例

    種本 真将, 眞部 建郎, 横川 和樹, 池田 和奈, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 久原 真, 松下 隆司, 下濱 俊

    臨床神経学   61 ( 1 )   55 - 55   2021.1

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  • 異なる臨床病型を呈し母にFUS遺伝子変異のmosaicismが示唆された家族性ALSの親子例

    久原 真, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 石川 亜貴, 櫻井 晃洋, 西山 亜由美, 元池 育子, 青木 正志, 青木 洋子, 下濱 俊

    臨床神経学   61 ( 1 )   55 - 55   2021.1

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  • A case of Charcot-Marie-Tooth disease type 2Z caused by MORC2 S87L mutation mimicking spinal muscular atrophy

    Daisuke Yamamoto, Ryosuke Oda, Shin Hisahara, Aki Ishikawa, Tomoo Ogi, Shun Shimohama

    Clinical Neurology   61 ( 4 )   262 - 264   2021

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Societas Neurologica Japonica  

    DOI: 10.5692/clinicalneurol.cn-001542

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  • Hyperemesis-induced Wernicke-Korsakoff Syndrome due to Hypergastrinemia during Long-term Treatment with Proton Pump Inhibitors.

    Rei Miyanaga, Shin Hisahara, Ikkei Ohhashi, Daisuke Yamamoto, Akihiro Matsumura, Syuuichirou Suzuki, Katsumasa Tanimoto, Masahiro Hirakawa, Jun Kawamata, Junji Kato, Shun Shimohama

    Internal medicine (Tokyo, Japan)   59 ( 21 )   2783 - 2787   2020.11

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    We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

    DOI: 10.2169/internalmedicine.5168-20

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  • Severe mononeuritis multiplex due to rheumatoid vasculitis in rheumatoid arthritis in sustained clinical remission for decades

    Masanobu Tanemoto, Shin Hisahara, Bungo Hirose, Kazuna Ikeda, Takashi Matsushita, Shuichiro Suzuki, Tatsuo Manabe, Tomihiro Imai, Shun Shimohama

    Internal Medicine   59 ( 5 )   705 - 710   2020.3

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    DOI: 10.2169/internalmedicine.3866-19

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  • 16SrRNA解析と膿瘍培養でFusobacterium nucleatumとStreptococcus intermediusの感染が判明した脳膿瘍の一例

    真部 建郎, 種本 真将, 小田 亮介, 松村 晃寛, 久原 真, 下濱 俊

    日本病院総合診療医学会雑誌   16 ( 臨増1 )   65 - 65   2020.2

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  • 16SrRNA解析と膿瘍培養でFusobacterium nucleatumとStreptococcus intermediusの感染が判明した脳膿瘍の一例

    曹 博, 種本 真将, 廣瀬 文吾, 池田 和奈, 津田 玲子, 真部 建郎, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 久原 真, 高橋 聡, 下濱 俊

    臨床神経学   60 ( 1 )   94 - 94   2020.1

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  • 神経変性疾患に対する脳血流123I-IMP-SPECTにおけるCIScore解析の検証

    松村 晃寛, 浅沼 治, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 眞部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   59 ( Suppl. )   S266 - S266   2019.11

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  • 神経変性疾患に対する脳血流123I-IMP-SPECTにおけるCIScore解析の検証

    松村 晃寛, 浅沼 治, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 眞部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   59 ( Suppl. )   S266 - S266   2019.11

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  • Transplantation of Mesenchymal Stem Cells Improves Amyloid-β Pathology by Modifying Microglial Function and Suppressing Oxidative Stress. Reviewed International journal

    Yokokawa K, Iwahara N, Hisahara S, Emoto MC, Saito T, Suzuki H, Manabe T, Matsumura A, Matsushita T, Suzuki S, Kawamata J, Sato-Akaba H, Fujii HG, Shimohama S

    Journal of Alzheimer's disease : JAD   72 ( 3 )   867 - 884   2019.10

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    Mesenchymal stem cells (MSC) are increasingly being studied as a source of cell therapy for neurodegenerative diseases, and several groups have reported their beneficial effects on Alzheimer's disease (AD). In this study using AD model mice (APdE9), we found that transplantation of MSC via the tail vein improved spatial memory in the Morris water maze test. Using electron paramagnetic resonance imaging to evaluate the in vivo redox state of the brain, we found that MSC transplantation suppressed oxidative stress in AD model mice. To elucidate how MSC treatment ameliorates oxidative stress, we focused on amyloid-β (Aβ) pathology and microglial function. MSC transplantation reduced Aβ deposition in the cortex and hippocampus. Transplantation of MSC also decreased Iba1-positive area in the cortex and reduced activated ameboid shaped microglia. On the other hand, MSC transplantation accelerated accumulation of microglia around Aβ deposits and prompted microglial Aβ uptake and clearance as shown by higher frequency of Aβ-containing microglia. MSC transplantation also increased CD14-positive microglia in vivo, which play a critical role in Aβ uptake. To confirm the effects of MSC on microglia, we co-cultured the mouse microglial cell line MG6 with MSC. Co-culture with MSC enhanced Aβ uptake by MG6 cells accompanied by upregulation of CD14 expression. Additionally, co-culture of MG6 cells with MSC induced microglial phenotype switching from M1 to M2 and suppressed production of proinflammatory cytokines. These data indicate that MSC treatment has the potential to ameliorate oxidative stress through modification of microglial functions, thereby improving Aβ pathology in AD model mice.

    DOI: 10.3233/JAD-190817

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  • 孤発性神経核内封入体病(NIID)の1例

    廣瀬 文吾, 松下 隆司, 鈴木 秀一郎, 久原 真, 上杉 春雄, 川又 純, 今井 富裕, 曽根 淳, 祖父江 元, 下濱 俊

    日本老年医学会雑誌   56 ( 4 )   545 - 545   2019.10

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  • 脊髄梗塞と鑑別を要しステロイドパルス療法で改善が得られた急性脊髄炎の1例

    種本 真将, 鈴木 秀一郎, 廣瀬 文吾, 池田 和奈, 久原 真, 下濱 俊

    神経治療学   36 ( 6 )   S282 - S282   2019.10

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  • Early administration of galantamine from preplaque phase suppresses oxidative stress and improves cognitive behavior in APPswe/PS1dE9 mouse model of Alzheimer's disease. Reviewed

    Saito T, Hisahara S, Iwahara N, Emoto MC, Yokokawa K, Suzuki H, Manabe T, Matsumura A, Suzuki S, Matsushita T, Kawamata J, Sato-Akaba H, Fujii HG, Shimohama S

    Free radical biology & medicine   145   20 - 32   2019.9

  • 悪性リンパ腫に合併した抗アクアポリン4抗体陽性散在性脳白質病変の1例

    山田 稔, 津田 玲子, 山本 大輔, 松村 晃寛, 岩原 直敏, 松下 隆司, 鈴木 秀一郎, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   59 ( 6 )   391 - 391   2019.6

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  • CD14 and Toll-Like Receptor 4 Promote Fibrillar Aβ42 Uptake by Microglia Through A Clathrin-Mediated Pathway. International journal

    Mai Fujikura, Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Tatsuo Manabe, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama

    Journal of Alzheimer's disease : JAD   68 ( 1 )   323 - 337   2019

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    We previously demonstrated that microglia play an essential role in clearance of amyloid-β (Aβ) in Alzheimer's disease (AD)-like pathology. Our prior work also showed that several receptors expressed on microglia participated in Aβ phagocytosis. However, clathrin-mediated endocytosis (CME), which is associated with production and release of Aβ in neurons, has received much less attention in the context of microglial Aβ uptake. To elucidate the detailed mechanisms of microglial Aβ uptake pathways, we focused on CD14 and Toll-like receptor 4 (TLR4), which have been shown to mediate fibrillar Aβ1 - 42 (fAβ42) phagocytosis in microglia. CD14 has also been known to control lipopolysaccharide-induced internalization of TLR4 in a clathrin-dependent manner. However, it remains unclear whether CD14 and TLR4 engage in CME in microglial fAβ42 uptake, including whether CD14 interacts with TLR4 in the process. In the present study, we found that CD14-positive microglia increased in an age-dependent manner in the cortex of AD model mice. Immunostaining showed that CD14 interacted with TLR4 to internalize fAβ42 in the mouse microglial cell line MG6. Knock-down of CD14 and TLR4 in MG6 cells significantly reduced intracellular fAβ42, showing their involvement in fAβ42 uptake. We also found that clathrin participated in fAβ42 uptake by MG6 cells. Furthermore, CD14 and TLR4 mediated fAβ42 uptake via clathrin-dependent mechanisms. These results indicate that CD14 and TLR4 participate not only in phagocytosis but also in clathrin-dependent fAβ42 internalization in microglia. These findings provide novel molecular understanding of microglial fAβ42 uptake, which could be of therapeutic relevance for AD.

    DOI: 10.3233/JAD-180904

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  • Evaluation of Mitochondrial Oxidative Stress in the Brain of a Transgenic Mouse Model of Alzheimer's Disease by in vitro Electron Paramagnetic Resonance Spectroscopy. Reviewed

    Manabe T, Matsumura A, Yokokawa K, Saito T, Fujikura M, Iwahara N, Matsushita T, Suzuki S, Hisahara S, Kawamata J, Suzuki H, Emoto MC, Fujii HG, Shimohama S

    Journal of Alzheimer's disease : JAD   67 ( 3 )   1079 - 1087   2019

  • Arterial spin labelingが早期診断に貢献した進行性多巣性白質脳症の一例

    松下 隆司, 中村 祐貴, 齋藤 太郎, 津田 玲子, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 津田 笑子, 久原 真, 川又 純, 菅原 太郎, 杉田 真太朗, 中道 一生, 下濱 俊

    NEUROINFECTION   23 ( 2 )   225 - 225   2018.10

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  • 筋力低下を主訴とした孤発性成人発症型ネマリンミオパチーの1例

    倉内 麗徳, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    日本老年医学会雑誌   55 ( 4 )   698 - 698   2018.10

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  • 脳血流IMP-SPECTにおけるCIScore解析によるDLB・AD鑑別の検証

    松村 晃寛, 浅沼 治, 蒲生 直希, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 真部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    Dementia Japan   32 ( 3 )   452 - 452   2018.9

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  • [Sporadic adult-onset neuronal intranuclear inclusion disease with abnormal electroretinogram, nerve conduction studies and somatosensory evoked potential].

    Bungo Hirose, Shin Hisahara, Haruo Uesugi, Jun Sone, Gen Sobue, Shun Shimohama

    Rinsho shinkeigaku = Clinical neurology   58 ( 6 )   407 - 410   2018.6

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    A 70-year-old man, a urinary retention of unknown origin from 10 years ago, decreased cognitive function from 4 years ago, vision impairment advanced a year ago. Brain MRI with DWI showed high intensity erea in the cortico-medullary junction. We diagnosed as intranuclear inclusion body disease (NIID) because of p62-positive intranuclear inclusion bodies by skin biopsy. Electroretinogram revealed amplitude reduction in the cone response superiority. Nerve conduction test showed mild conduction velocity reduction. Furthermore, in the somatosensory evoked potential of the lower limb, latency of the first cortical component was prolonged. These electrophysiological abnormalities were considered to be associated with the pathological features of NIID.

    DOI: 10.5692/clinicalneurol.cn-001154

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  • 網膜電図、末梢神経伝導検査、体性感覚誘発電位異常を伴った孤発性神経核内封入体病の1例

    廣瀬 文吾, 久原 真, 上杉 春雄, 曽根 淳, 祖父江 元, 下濱 俊

    臨床神経学   58 ( 6 )   407 - 410   2018.6

  • Non-HIV-PMLの診断後2年以上生存した1症例

    中村 祐貴, 齋藤 太郎, 津田 玲子, 山本 大輔, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 津田 笑子, 久原 真, 川又 純, 下濱 俊, 菅原 太郎, 杉田 真太朗, 中道 一生

    臨床神経学   58 ( 5 )   358 - 358   2018.5

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  • Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis. International journal

    Yusei Miyazaki, Masaaki Niino, Eri Takahashi, Masako Suzuki, Masanori Mizuno, Shin Hisahara, Toshiyuki Fukazawa, Itaru Amino, Fumihito Nakano, Masakazu Nakamura, Sachiko Akimoto, Naoya Minami, Naoto Fujiki, Shizuki Doi, Shun Shimohama, Yasuo Terayama, Seiji Kikuchi

    Clinical immunology (Orlando, Fla.)   187   95 - 101   2018.2

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    Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease.

    DOI: 10.1016/j.clim.2017.10.009

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  • 尿閉が先行し、経過中に網膜電図異常を伴う視力低下を認めた孤発性神経核内封入体病(NIID)の1例

    廣瀬 文吾, 土谷 円花, 宮永 怜, 眞部 建郎, 山本 大輔, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 久原 真, 川又 純, 上杉 春雄, 今井 富裕, 下濱 俊, 曽根 淳, 祖父江 元

    臨床神経学   57 ( 12 )   815 - 815   2017.12

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  • 修正型電気けいれん療法(mECT)施行後、著明なparkinsonismの改善を認めた重度精神症状合併Parkinson病の2例 Reviewed

    大橋 一慶, 鈴木 秀一郎, 山本 大輔, 松村 晃寛, 松下 隆司, 久原 真, 川又 純, 下濱 俊, 石田 智隆, 松山 清治, 河西 千秋, 柏木 智則

    臨床神経学   57 ( 12 )   815 - 815   2017.12

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  • Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis Reviewed

    Daisuke Yamamoto, Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Rika Yamauchi, Shin Hisahara, Jun Kawamata, Shun Shimohama

    CLINICAL NEUROPHYSIOLOGY   128 ( 11 )   2309 - 2317   2017.11

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    DOI: 10.1016/j.clinph.2017.08.030

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  • 四肢腱反射が亢進し、病的反射が陽性であったギランバレー症候群の1例

    倉内 麗徳, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   57 ( 6 )   321 - 321   2017.6

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  • 急性硬膜下血腫開頭術後に発症した硬膜動静脈瘻の1例

    大橋 一慶, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 宮田 圭, 下濱 俊

    臨床神経学   57 ( 6 )   324 - 324   2017.6

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  • 末梢神経障害を伴った強皮症の1例

    山田 稔, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 村原 貴史, 松下 隆司, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   57 ( 6 )   322 - 322   2017.6

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  • Role of Suppressor of Cytokine Signaling 3 (SOCS3) in Altering Activated Microglia Phenotype in APPswe/PS1dE9 Mice. International journal

    Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Mai Fujikura, Tatsuo Manabe, Hiromi Suzuki, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama

    Journal of Alzheimer's disease : JAD   55 ( 3 )   1235 - 1247   2017

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    In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation. In the present study, we analyzed in vivo expressions of pro-inflammatory cytokines (M1 microglial markers), M2 microglial markers, and suppressor of cytokine signaling (SOCS) family, and examined the microglial phenotypic profile in APPswe/PS1dE9 mice. Then we compared the in vitro gene expression patterns of Aβ- and lipopolysaccharide (LPS)-stimulated primary-cultured microglia. Microglia in APPswe/PS1dE9 mice exhibited an M1-like phenotype, expressing tumor necrosis factor α (TNFα) but not interleukin 6 (IL6). Aβ-stimulated primary-cultured microglia also expressed TNFα but not IL6, whereas LPS-stimulated primary-cultured microglia expressed both pro-inflammatory cytokines. Furthermore, both microglia in APPswe/PS1dE9 mice and Aβ-stimulated primary-cultured microglia expressed SOCS3. Reduction of SOCS3 expression in Aβ-challenged primary-cultured microglia resulted in upregulation of IL6 expression. Our findings indicate that SOCS3 suppresses complete polarization to M1 phenotype through blocking IL6 production, and Aβ-challenged primary-cultured microglia replicate the in vivo gene expression pattern of microglia in APPswe/PS1dE9 mice. Aβ may induce the M1-like phenotype through blocking of IL6 by SOCS3.

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  • 右正中神経前腕部で伝導ブロックを呈し、多巣性運動ニューロパチーが疑われた1例

    倉内 麗徳, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   56 ( 11 )   801 - 801   2016.11

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  • 下垂足を呈し末梢神経障害との鑑別を要した胸髄症の1例

    池田 和奈, 石田 智隆, 蒲生 直希, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 久原 真, 村原 貴史, 松下 隆司, 松村 晃寛, 齊藤 正樹, 川又 純, 下濱 俊, 今井 富裕

    臨床神経学   56 ( 11 )   802 - 802   2016.11

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  • けいれん重積を来したAngiomyxomatous tumorの一例

    横川 和樹, 池田 和奈, 越智 龍太郎, 村原 貴史, 臼井 桂子, 松下 隆司, 松村 晃寛, 津田 笑子, 鈴木 秀一郎, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊, 江夏 怜, 三國 信啓, 杉田 真太朗, 長谷川 匡

    臨床神経学   56 ( 11 )   802 - 802   2016.11

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  • 肥厚性硬膜炎様の頭部MRI所見を呈したびまん性大細胞型B細胞リンパ腫の1例

    蒲生 直希, 池田 和奈, 鈴木 秀一郎, 津田 笑子, 村原 貴史, 松下 隆司, 松村 晃寛, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   56 ( 11 )   804 - 804   2016.11

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  • FUS/TLS R521L変異を認めた家族性筋萎縮性側索硬化症(FALS)の1家系

    大橋 一慶, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 鈴木 昭治, 下濱 俊

    臨床神経学   56 ( 11 )   803 - 803   2016.11

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  • 首下がりで発症した重症筋無力症の1例

    山田 稔, 倉内 麗徳, 村原 貴史, 津田 笑子, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 久原 真

    日本老年医学会雑誌   53 ( 4 )   441 - 441   2016.10

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  • ANCA-negative granulomatosis with polyangiitis presenting with orbital apex syndrome and recurrent pachymeningitis: A case report. International journal

    Shin Hisahara, Minoru Yamada, Yousuke Matsuura, Emiko Tsuda, Yukinori Akiyama, Masaki Saitoh, Jun Kawamata, Nobuhiro Mikuni, Shun Shimohama

    Journal of the neurological sciences   368   175 - 7   2016.9

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  • Fingolimod suppresses bone resorption in female patients with multiple sclerosis. International journal

    Yusei Miyazaki, Masaaki Niino, Ippei Kanazawa, Masako Suzuki, Masanori Mizuno, Shin Hisahara, Toshiyuki Fukazawa, Eri Takahashi, Itaru Amino, Ryutaro Ochi, Masakazu Nakamura, Sachiko Akimoto, Naoya Minami, Naoto Fujiki, Shizuki Doi, Shun Shimohama, Yasuo Terayama, Seiji Kikuchi

    Journal of neuroimmunology   298   24 - 31   2016.9

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    Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory activity of multiple sclerosis (MS), and has been shown to suppress osteoporosis in mouse models. In this study, levels of bone turnover markers were quantified in serum and urine samples from MS patients treated with fingolimod. Compared with untreated MS patients and healthy controls, fingolimod-treated MS patients had a significantly lower level of the bone resorption marker type I collagen cross-linked N-telopeptide in urine. This finding was prominent in female but was not seen in male subjects. Our results suggest that fingolimod may have a beneficial effect on bone mass loss in female MS patients.

    DOI: 10.1016/j.jneuroim.2016.06.007

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  • Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis: a cross-sectional study. Reviewed International journal

    Yuri Nakamura, Takuya Matsushita, Shinya Sato, Masaaki Niino, Toshiyuki Fukazawa, Satoshi Yoshimura, Shin Hisahara, Noriko Isobe, Shun Shimohama, Mitsuru Watanabe, Kazuto Yoshida, Hideki Houzen, Yusei Miyazaki, Ryo Yamasaki, Seiji Kikuchi, Jun-Ichi Kira

    Journal of neuroinflammation   13 ( 1 )   239 - 239   2016.9

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    BACKGROUND: Higher latitude and human leukocyte antigen (HLA)-DRB1*04:05 increase susceptibility to multiple sclerosis (MS) in the Japanese population, but their effects on disease severity are unknown. We aimed to clarify the effects of latitude and the HLA-DRB1 and HLA-DPB1 genes on disease severity in Japanese patients with MS. METHODS: We enrolled 247 MS patients and 159 healthy controls (HCs) from the northernmost main island of Japan, Hokkaido Island (42-45° north), and 187 MS patients and 235 HCs from the southern half (33-35° north) of the Japanese archipelago (33-45° north). We genotyped HLA-DRB1 and HLA-DPB1 alleles, compared demographic features, and analyzed factors contributing to differences in clinical and laboratory findings between MS patients from southern and northern Japan. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Kurtzke's Expanded Disability Status Scale score according to disease duration, was used to estimate disease severity. RESULTS: The HLA-DRB1*04:05 and DRB1*15:01 alleles conferred susceptibility to MS in our Japanese population (p (corr) = 0.0004 and p (corr) = 0.0019, respectively). Southern patients had higher MSSS scores than northern patients (p = 0.003). Northern patients had higher frequencies of brain lesions meeting the Barkhof criteria (Barkhof brain lesions) and cerebrospinal fluid (CSF) IgG abnormalities than southern patients (p = 0.0012 and p < 0.0001, respectively). DRB1*04:05-positive MS patients had lower MSSS scores and lower frequencies of Barkhof brain lesions and CSF IgG abnormalities than DRB1*04:05-negative MS patients (p = 0.0415, p = 0.0026, and p < 0.0001, respectively). Multivariate analyses revealed that latitude and DRB1*04:05 were independently associated with the lowest quartile of MSSS and that latitude was positively associated with Barkhof brain lesions and CSF IgG abnormalities. DRB1*04:05 was negatively associated with these parameters. MSSS was decreased by 0.57 per DRB1*04:05 allele (p = 0.0198). CONCLUSIONS: Living at a higher latitude and carrying the DRB1*04:05 allele independently lessens MS symptom severity as defined by MSSS. However, these factors influence the frequency of Barkhof brain lesions and CSF IgG abnormalities in opposite ways; higher latitude increases the frequency of Barkhof brain lesions and CSF IgG abnormalities, whereas DRB1*04:05 decreases them.

    DOI: 10.1186/s12974-016-0695-3

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  • Oxidation and interaction of DJ-1 with 20S proteasome in the erythrocytes of early stage Parkinson's disease patients. International journal

    Yoshiro Saito, Yoko Akazawa-Ogawa, Akihiro Matsumura, Kazumasa Saigoh, Sayoko Itoh, Kenta Sutou, Mayuka Kobayashi, Yuichiro Mita, Mototada Shichiri, Shin Hisahara, Yasuo Hara, Harutoshi Fujimura, Hiroyuki Takamatsu, Yoshihisa Hagihara, Yasukazu Yoshida, Takao Hamakubo, Susumu Kusunoki, Shun Shimohama, Noriko Noguchi

    Scientific reports   6   30793 - 30793   2016.7

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    Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33). Elevated oxDJ-1 levels were also observed in a non-human primate PD model. Biochemical analysis of oxDJ-1 in erythrocyte lysates showed that oxDJ-1 formed dimer and polymer forms, and that the latter interacts with 20S proteasome. These results clearly indicate a biochemical alteration in the blood of PD patients, which could be utilized as an early diagnosis marker for PD.

    DOI: 10.1038/srep30793

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  • 遅発性顔面神経麻痺を呈したフィッシャー症候群の1例

    清水 将輝, 平野 理都子, 齋藤 太郎, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 廣瀬 文吾, 山田 稔, 下濱 俊

    臨床神経学   56 ( 6 )   453 - 453   2016.6

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  • MFN2遺伝子点変異を有するシャルコー・マリー・トゥース病の1例

    横川 和樹, 池田 和奈, 村原 貴史, 齊藤 正樹, 鈴木 秀一郎, 津田 笑子, 林 貴士, 久原 真, 川又 純, 下濱 俊, 外山 祐一郎

    臨床神経学   56 ( 6 )   453 - 453   2016.6

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  • 出産直後に再発を認めた視神経脊髄炎の1例

    池田 和奈, 安食 さえ子, 津田 笑子, 久原 真, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 川又 純, 下濱 俊

    臨床神経学   56 ( 6 )   447 - 447   2016.6

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  • 嚥下障害が残存した抗SRP抗体陽性ミオパチーの2症例

    中村 祐貴, 齋藤 太郎, 松下 隆司, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊, 岡本 賢三

    臨床神経学   56 ( 6 )   452 - 452   2016.6

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  • 肛門周囲の感覚障害で発症し、前立腺生検にて診断に至った血管内リンパ腫(IVL)の1例

    齋藤 太郎, 中村 祐貴, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊, 村瀬 和幸, 高田 弘一

    臨床神経学   56 ( 6 )   451 - 451   2016.6

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  • ネフローゼ症候群、潰瘍性大腸炎、再生不良性貧血を合併した抗MuSK抗体陽性重症筋無力症の1例

    安食 さえ子, 横川 和樹, 津田 笑子, 久原 真, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   56 ( 6 )   452 - 452   2016.6

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  • 三叉神経障害で発症した多発性硬化症の一例

    平野 理都子, 中村 祐貴, 齋藤 太郎, 眞部 建郎, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   56 ( 6 )   447 - 447   2016.6

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  • Impaired post-tetanic potentiation of muscle twitch in myasthenia gravis Reviewed

    Daisuke Yamamoto, Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Rika Yamauchi, Shin Hisahara, Jun Kawamata, Shun Shimohama

    CLINICAL NEUROPHYSIOLOGY   127 ( 2 )   1689 - 1693   2016.2

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    DOI: 10.1016/j.clinph.2015.10.037

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  • メフロキンおよびミルタザピン投与によりJCV DNA-PCRが陰性化したPMLの1例

    横川 和樹, 松浦 洋介, 池田 和奈, 津田 笑子, 久原 真, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 川又 純, 下濱 俊

    臨床神経学   55 ( 12 )   945 - 945   2015.12

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  • 当施設における筋萎縮性側索硬化症(ALS)患者の人工呼吸器選択について

    川又 純, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 山内 理香, 齊藤 正樹, 久原 真, 下濱 俊

    臨床神経学   55 ( Suppl. )   S378 - S378   2015.12

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  • Tolosa-Hunt症候群と鑑別が困難であった肥厚性硬膜炎の1例

    安食 さえ子, 中村 祐貴, 山田 稔, 松下 隆司, 村原 貴史, 矢澤 省吾, 林 貴士, 鈴木 秀一郎, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   948 - 948   2015.12

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  • GalNAc-GD1a IgM抗体陽性急性運動感覚性軸索型ニューロパチー(AMSAN)の1例

    齋藤 太郎, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 廣瀬 文吾, 鈴木 昭治, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • 嚥下障害が遷延した浸透圧性脱髄症候群の1例

    山田 稔, 村原 貴史, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • 低血糖をきたした非福山型先天性筋ジストロフィーの1例

    中村 祐貴, 吉崎 那保, 山田 稔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 12 )   947 - 947   2015.12

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  • パーキンソニズムを呈するSCA6の1例

    池田 和奈, 大岩 修太郎, 津田 笑子, 齊藤 正樹, 鈴木 秀一郎, 林 貴士, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 12 )   945 - 945   2015.12

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  • 短期間で再増悪した脱髄性ニューロパチーの一例

    加賀 理都子, 中村 祐貴, 山田 稔, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • 当初CLIPPERSを疑い難治に経過した脳炎の1例

    野中 隆行, 山田 稔, 村原 貴史, 安食 さえ子, 齋藤 太郎, 鈴木 秀一郎, 津田 笑子, 山内 理香, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 12 )   946 - 946   2015.12

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  • 肥厚性硬膜炎、大脳病変を呈した多発血管炎性肉芽腫症が疑われた1例

    山田 稔, 松浦 洋介, 津田 笑子, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 9 )   682 - 682   2015.9

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  • 多彩な非運動症状を呈した重症筋無力症の1例

    倉内 麗徳, 津田 笑子, 山本 大輔, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 9 )   682 - 682   2015.9

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  • Metronidazoleにより脳症と末梢神経障害を来した1例

    廣瀬 文吾, 小林 未来, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 9 )   681 - 681   2015.9

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  • ボリコナゾールによる診断的治療が有用であった深在性アスペルギルス症の1例

    横川 和樹, 山本 大輔, 鈴木 秀一郎, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    神経治療学   32 ( 5 )   787 - 787   2015.9

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  • Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis. Reviewed International journal

    Niino M, Sato S, Fukazawa T, Yoshimura S, Hisahara S, Matsushita T, Isobe N, Yoshida K, Houzen H, Miyazaki Y, Shimohama S, Kikuchi S, Kira J

    Multiple sclerosis (Houndmills, Basingstoke, England)   21 ( 9 )   1112 - 1120   2015.8

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    BACKGROUND: It is unclear whether the prevalence of oligoclonal IgG bands (OCBs) in multiple sclerosis (MS) is different between northern and southern regions of Asia. OBJECTIVE: This study aimed to compare the prevalence of OCBs and positive cerebrospinal fluid (CSF) findings between northern and southern regions of Japan and to investigate the association of these CSF findings with HLA-DRB1 alleles. METHODS: The study included 180 MS patients from Hokkaido (northern Japan) and 184 patients from Kyushu (southern Japan). The IgG index was defined as increased if it was >0.658. Presence of CSF OCBs and/or increased IgG index was defined as positive CSF findings. RESULTS: Positive CSF findings and OCB positivity were significantly higher in MS patients from Hokkaido than in those from Kyushu (p < 0.0001 for both). Logistic regression analysis revealed that after adjusting for covariates that can be related to abnormal CSF IgG production, the geographic region (Hokkaido) showed odds ratios (ORs) of 4.08 and 2.57, whereas the HLA-DRB1*04:05 allele showed ORs of 0.36 and 0.30 for positive CSF findings and OCB positivity, respectively. CONCLUSIONS: The results indicate that latitude and HLA-DRB1 alleles independently affect the emergence of CSF IgG abnormalities in Japanese patients with MS.

    DOI: 10.1177/1352458514560924

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  • Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging. Reviewed

    Matsumura A, Emoto MC, Suzuki S, Iwahara N, Hisahara S, Kawamata J, Suzuki H, Yamauchi A, Sato-Akaba H, Fujii HG, Shimohama S

    Free radical biology & medicine   85   165 - 173   2015.8

  • A Heterozygous Missense Mutation in Adolescent-Onset Very Long-Chain Acyl-CoA Dehydrogenase Deficiency with Exercise-Induced Rhabdomyolysis Reviewed

    Shin Hisahara, Takashi Matsushita, Hiroyasu Furuyama, Go Tajima, Yosuke Shigematsu, Tomihiro Imai, Shun Shimohama

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   235 ( 4 )   305 - 310   2015.4

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    DOI: 10.1620/tjem.235.305

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  • 後骨間神経麻痺様の経過を呈した若年性一側上肢筋萎縮症(平山病)の一例

    倉内 麗徳, 山本 大輔, 池田 和奈, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 2 )   129 - 129   2015.2

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  • 大脳皮質基底核変性症(CBD)と筋萎縮性側索硬化症(ALS)の合併が疑われた1例

    小林 未来, 廣瀬 文吾, 山本 大輔, 鈴木 秀一郎, 岩原 直敏, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 2 )   131 - 131   2015.2

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  • 診断に苦慮した中枢神経サルコイドーシスの1例

    山田 稔, 池田 和奈, 廣瀬 文吾, 小林 未来, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 2 )   132 - 132   2015.2

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  • 頸髄病変にopen-ring状の造影効果を認めた一例

    松浦 洋介, 山本 大輔, 廣瀬 文吾, 小林 未来, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   55 ( 2 )   132 - 132   2015.2

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  • Intravenous mesenchymal stem cell administration exhibits therapeutic effects against 6-hydroxydopamine-induced dopaminergic neurodegeneration and glial activation in rats. Reviewed International journal

    Suzuki S, Kawamata J, Iwahara N, Matsumura A, Hisahara S, Matsushita T, Sasaki M, Honmou O, Shimohama S

    Neuroscience letters   584   276 - 281   2015.1

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    To explore a novel therapy against Parkinson's disease (PD), we evaluated the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs), pluripotent stromal cells with secretory potential of various neurotrophic and anti-inflammatory factors, in a hemi-parkinsonian rat model. The unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were injected hBM-MSCs (1.0 × 10(7)cells) or PBS intravenously 16 days after lesioning. Administration of hBM-MSCs inhibited methamphetamine-stimulated rotational behavior at 7, 14, 21 and 28 days after transplantation. Immunohistochemical analysis also showed that number of TH-positive neurons in the substantia nigra pars compacta was significantly preserved in hBM-MSCs-transplanted rats compared to sham-operated rats, whereas the immunoreactivity of ionized calcium binding adaptor molecule 1 was markedly inhibited. In this study, we demonstrated the therapeutic effects of intravenous hBM-MSCs administration in parkinsonian model rats presenting distinct parkinsonian phenotype at 16 days after 6-OHDA lesioning. The favorable findings raise the possibility that hBM-MSCs could be a novel therapeutic option to promote survival of dopaminergic neurons in PD.

    DOI: 10.1016/j.neulet.2014.10.039

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  • Temporal changes of CD68 and α7 nicotinic acetylcholine receptor expression in microglia in Alzheimer's disease-like mouse models. Reviewed International journal

    Matsumura A, Suzuki S, Iwahara N, Hisahara S, Kawamata J, Suzuki H, Yamauchi A, Takata K, Kitamura Y, Shimohama S

    Journal of Alzheimer's disease : JAD   44 ( 2 )   409 - 423   2015

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    We previously reported that activated microglia are involved in amyloid-β (Aβ) clearance and that stimulation of α7 nicotinic acetylcholine receptors (nAChR) in microglia enhances Aβ clearance. Nevertheless, how microglia and α7 nAChR in microglia are affected in Alzheimer's disease (AD) remains unknown. The present study aimed to collect fundamental data for considering whether microglia are potential targets for AD treatment and the appropriate timing of therapeutic intervention, by evaluating the temporal changes of Aβ, microglia, neurons, presynapses, and α7 nAChR by immunohistochemical studies in mouse models of AD. In an Aβ-injected AD mouse model, we observed early accumulation of CD68-positive microglia at Aβ deposition sites and gradual reduction of Aβ. Microglia were closely associated with Aβ deposits, and were confirmed to participate in clearing Aβ. In a transgenic mouse model of AD, we observed an increase in Aβ deposition from 6 months of age, followed by a gradual increase in microglial accumulation at Aβ deposit sites. Activated microglia in APdE9 mice showed two-step transition: a CD68-negative activated form at 6-9 months and a CD68-positive form from 12 months of age. In addition, α7 nAChR in microglia increased markedly at 6 months of age when activated microglia appeared for the first time, and decreased gradually coinciding with the increase of Aβ deposition. These findings suggest that early microglial activation is associated with α7 nAChR upregulation in microglia in APdE9 mice. These novel findings are important for the development of new therapeutic strategy for AD.

    DOI: 10.3233/JAD-141572

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  • Long-term clinical and radiological improvement of chronic acquired hepatocerebral degeneration after obliteration of portosystemic shunt: Report of a case Reviewed

    Shin Hisahara, Takashi Matsushita, Mizuki Kitamura, Shinichi Mezawa, Michio Nonaka, Tomihiro Imai, Shun Shimohama

    JOURNAL OF THE NEUROLOGICAL SCIENCES   346 ( 1-2 )   303 - 306   2014.11

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    DOI: 10.1016/j.jns.2014.07.068

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  • 全般性認知機能障害を伴わない緩徐進行性失行の1例

    池田 和奈, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   54 ( 10 )   837 - 837   2014.10

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  • Alzheimer病モデル動物脳におけるmicrogliaの経時的動態

    松村 晃寛, 鈴木 紘美, 山内 綾乃, 岩原 直敏, 鈴木 秀一郎, 久原 真, 川又 純, 高田 和幸, 北村 佳久, 下濱 俊

    Dementia Japan   28 ( 4 )   481 - 481   2014.10

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  • 家族歴のある自己免疫性脳症と考えられた一例

    田中 真理子, 村原 貴史, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   54 ( 10 )   834 - 834   2014.10

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  • Painful tonic spasmを呈したNMOSDの1例

    藤倉 舞, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   54 ( 10 )   834 - 834   2014.10

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  • 脊髄性筋萎縮症様の所見および不整脈、心機能低下を呈し、新規LaminA/C遺伝子変異を認めた1例

    岩原 直敏, 山本 大輔, 津田 玲子, 林 貴士, 鈴木 秀一郎, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   54 ( 10 )   838 - 838   2014.10

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  • 診断に苦慮した中枢神経サルコイドーシスの1例

    池田 和奈, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    神経治療学   31 ( 5 )   627 - 627   2014.9

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  • SIRT1 regulates lamellipodium extension and migration of melanoma cells. Reviewed International journal

    Risa Kunimoto, Kowichi Jimbow, Akihiko Tanimura, Masahiro Sato, Kouhei Horimoto, Takashi Hayashi, Shin Hisahara, Toshiya Sugino, Tomohisa Hirobe, Toshiharu Yamashita, Yoshiyuki Horio

    The Journal of investigative dermatology   134 ( 6 )   1693 - 1700   2014.6

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    Melanoma is highly metastatic, but the mechanism of melanoma cell migration is still unclear. We found that melanoma cells expressed the nicotinamide adenine dinucleotide-dependent protein deacetylase SIRT1 in the cytoplasm. Cell membrane extension and migration of melanoma cells were inhibited by SIRT1 inhibitors or SIRT1 knockdown, whereas SIRT1 activators enhanced elongation of protrusion and cellular motility. In B16F1 cells, growth factor stimulation induced lamellipodium extension, a characteristic feature at the leading edge of migrating cells, and SIRT1 was found in the lamellipodium. SIRT1 inhibitor nicotinamide (NAM) or SIRT1 small interfering RNAs suppressed the lamellipodium extension by serum or platelet-derived growth factor (PDGF). The lamellipodium formation by dominant-active Rac1 was also inhibited by NAM, a SIRT1 inhibitor. NAM inhibited the accumulation of phosphorylated Akt at the submembrane by serum or PDGF. Using fluorescence resonance energy transfer, we found that NAM impaired PDGF-dependent increase in the phosphatidylinositol-3,4,5-trisphosphate level at the leading edge. NAM inhibited the abdominal metastasis of transplanted B16F1 melanoma cells in C57BL6/J mice and improved survival. Finally, SIRT1-knockdown B16F1 cells showed significantly reduced metastasis in transplanted mice compared with that in control B16F1 cells. These results indicate that SIRT1 inhibition is a strategy to suppress metastasis of melanoma cells.

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  • 3-[(2,4-Dimethoxy)benzylidene]-anabaseine dihydrochloride protects against 6-hydroxydopamine-induced parkinsonian neurodegeneration through α7 nicotinic acetylcholine receptor stimulation in rats. Reviewed International journal

    Suzuki S, Kawamata J, Matsushita T, Matsumura A, Hisahara S, Takata K, Kitamura Y, Kem W, Shimohama S

    Journal of neuroscience research   91 ( 3 )   462 - 471   2013.3

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    To explore a novel therapy against Parkinson's disease through enhancement of α7 nicotinic acetylcholine receptor (nAChR), we evaluated the neuroprotective effects of 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA; GTS-21), a functionally selective α7 nAChR agonist, in a rat 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. Microinjection of 6-OHDA into the nigrostriatal pathway of rats destroys dopaminergic neurons selectively. DMXBA dose dependently inhibited methamphetamine-stimulated rotational behavior and dopaminergic neuronal loss induced by 6-OHDA. The protective effects were abolished by methyllycaconitine citrate salt hydrate, an α7 nAChR antagonist. Immunohistochemical study confirmed abundant α7 nAChR expression in the cytoplasm of dopaminergic neurons. These results indicate that DMXBA prevented 6-OHDA-induced dopaminergic neuronal loss through stimulating α7 nAChR in dopaminergic neurons. Injection of 6-OHDA elevated immunoreactivities to glial markers such as ionized calcium binding adaptor molecule 1, CD68, and glial fibrillary acidic protein in the substantia nigra pars compacta of rats. In contrast, these immunoreactivities were markedly inhibited by comicroinjection of DMXBA. Microglia also expressed α7 nAChR in both resting and activated states. Hence, we hypothesize that DMXBA simultaneously affects microglia and dopaminergic neurons and that both actions lead to dopaminergic neuroprotection. The findings that DMXBA attenuates 6-OHDA-induced dopaminergic neurodegeneration and glial activation in a rat model of Parkinson's disease raisethe possibility that DMXBA could be a novel therapeutic compound to prevent Parkinson's disease development.

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  • 原因不明のまま治療開始した頭蓋底病変の予後 多発性脳神経障害を呈した感染症を中心に

    松村 晃寛, 今井 富裕, 齊藤 正樹, 久原 真, 下濱 俊

    臨床神経学   53 ( 1 )   9 - 18   2013.1

  • [Treatment outcome of patients with cranial base lesions of unknown etiology: focusing on infectious cases with multiple cranial nerve disorders].

    Akihiro Matsumura, Tomihiro Imai, Masaki Saito, Shin Hisahara, Shun Shimohama

    Rinsho shinkeigaku = Clinical neurology   53 ( 1 )   9 - 18   2013

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    Involvement of cranial nerves caused by cranial base lesions manifests diverse symptoms according to the localization of lesions. These localization-related symptoms are classified into syndromes such as orbital apex syndrome, cavernous sinus syndrome, and jugular foramen syndrome. Since the lesions may have various etiologies including infection, inflammation and tumor, etiological diagnosis should be performed simultaneously if possible. However, previous reports have described poor and/or fatal outcome following inappropriate treatment mainly due to difficulties in making a definitive pathological diagnosis. Nineteen patients with multiple cranial nerve involvement caused by skull base lesions were enrolled over the past 12 years. The patients were divided into an "infectious" group (n=11) and a "noninfectious" group (n=8) based on the final diagnosis. Chi-square analysis was conducted to examine the sensitivity and specificity of various factors including patient characteristics, clinical course and treatment response in infectious and noninfectious groups. Consequently, we identified some patients with good outcome irrespective of infectious or noninfectious etiology, even though a pathological diagnosis was not reached before the initial treatment. These patients with good outcome consistently received antifungal therapy in the early stage if infectious etiologies were suspected. We recommend conducting diagnostic therapy with antifungal drugs in patients with skull base lesions of unknown origin although infection cannot be excluded, when a pathological diagnosis is difficult due to various patient conditions.

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  • Pure autonomic neuropathyの臨床病理学的特徴

    小池 春樹, 橋本 里奈, 冨田 稔, 川頭 祐一, 飯島 正博, 児矢野 繁, 桃尾 隆之, 湯浅 浩之, 三竹 重久, 東原 真奈, 海田 賢一, 山本 大輔, 久原 真, 下濱 俊, 中江 啓晴, 城倉 健, 祖父江 元

    臨床神経学   52 ( 12 )   1542 - 1542   2012.12

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  • 呼吸不全の進行と横隔神経複合筋活動電位の低下が相関しないALSの臨床的特徴

    山内 理香, 今井 富裕, 保月 隆良, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   52 ( 12 )   1607 - 1607   2012.12

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  • The spectrum of clinicopathological features in pure autonomic neuropathy. International journal

    Haruki Koike, Rina Hashimoto, Minoru Tomita, Yuichi Kawagashira, Masahiro Iijima, Shigeru Koyano, Takayuki Momoo, Hiroyuki Yuasa, Shigehisa Mitake, Mana Higashihara, Kenichi Kaida, Daisuke Yamamoto, Shin Hisahara, Shun Shimohama, Yoshiharu Nakae, Ken Johkura, Steven Vernino, Gen Sobue

    Journal of neurology   259 ( 10 )   2067 - 75   2012.10

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    We assessed the clinicopathological features of nine patients with pure autonomic neuropathy, that is, neuropathy without sensory or motor deficits. The duration from symptom onset to diagnosis ranged from 1 month to 13 years. Of eight patients in whom serum antiganglionic acetylcholine receptor antibody was determined, four were positive. All patients who tested positive for this antibody manifested widespread autonomic dysfunction, with the exception of one patient who only experienced orthostatic hypotension. However, patients who were negative for the antiganglionic acetylcholine receptor antibody presented with partial autonomic failure. One of these patients had diffuse parasympathetic failure and generalized hypohidrosis but no orthostatic hypotension, which is clinically compatible with postganglionic cholinergic dysautonomia. Electron microscopic examination revealed a variable degree of reduction in unmyelinated fibers. Compared with normal controls, the patients had a significantly increased density of collagen pockets (p < 0.05). Additionally, the percentage of Schwann cell subunits with axons (out of the total number of Schwann cell subunits associated with unmyelinated fibers) was significantly decreased (p < 0.01). The density of unmyelinated fibers tended to decrease with increasing time between the onset of autonomic symptoms and biopsy (p < 0.05). In conclusion, the clinical and pathological features of pure autonomic neuropathy vary in terms of progression, autonomic involvement, presence of the antiganglionic acetylcholine receptor antibody, and loss of unmyelinated fibers.

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  • Early effect of tacrolimus in improving excitation-contraction coupling in myasthenia gravis Reviewed

    Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Rika Yamauchi, Masaki Saitoh, Shin Hisahara, Hiroaki Yoshikawa, Masakatsu Motomura, Jun Kawamata, Shun Shimohama

    CLINICAL NEUROPHYSIOLOGY   123 ( 9 )   1886 - 1890   2012.9

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    DOI: 10.1016/j.clinph.2012.01.017

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  • Relationship between dysphagia and depressive states in patients with Parkinson's disease

    Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisahara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori

    Parkinson's Disease: Diagnosis, Treatment and Prognosis   201 - 208   2012.7

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  • Contribution of anti-ryanodine receptor antibody to impairment of excitation-contraction coupling in myasthenia gravis Reviewed

    Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Hiroaki Yoshikawa, Rika Yamauchi, Masaki Saitoh, Shin Hisahara, Masakatsu Motomura, Jun Kawamata, Shun Shimohama

    CLINICAL NEUROPHYSIOLOGY   123 ( 6 )   1242 - 1247   2012.6

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    DOI: 10.1016/j.clinph.2011.10.038

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  • 筋萎縮性側索硬化症における鼻腔吸気圧測定『開放法』と『閉鎖法』

    山内 理香, 山本 大輔, 松村 晃寛, 津田 笑子, 保月 隆良, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   51 ( 12 )   1365 - 1365   2011.12

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  • 赤血球画分を用いた酸化DJ-1定量の検討

    松村 晃寛, 久原 真, 齊藤 正樹, 川又 純, 今井 富裕, 下濱 俊, 斎藤 芳郎, 野口 範子, 二木 鋭雄

    臨床神経学   51 ( 12 )   1266 - 1266   2011.12

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  • 咬筋のend-plateは生理的刺激頻度では伝達ブロックが起きにくい

    今井 富裕, 津田 笑子, 山内 理香, 保月 隆良, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

    臨床神経学   51 ( 12 )   1461 - 1461   2011.12

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  • Relationship between dysphagia and depressive states in patients with Parkinson&apos;s disease Reviewed

    Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisahara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori

    PARKINSONISM & RELATED DISORDERS   17 ( 6 )   437 - 439   2011.7

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    DOI: 10.1016/j.parkreldis.2011.03.006

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  • Dopamine Receptors and Parkinson's Disease

    Shin Hisahara, Shun Shimohama

    International Journal of Medicinal Chemistry   2011.6

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    DOI: 10.1155/2011/403039

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  • FAP ATTR Val30Metの1弧発例

    山本 大輔, 津田 笑子, 今井 富裕, 林 貴士, 齊藤 正樹, 久原 真, 下濱 俊

    臨床神経学   51 ( 3 )   226 - 226   2011.3

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  • 脳有鉤嚢虫症の1例

    保月 隆良, 山本 大輔, 松村 晃寛, 津田 玲子, 津田 笑子, 山内 理香, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   51 ( 3 )   226 - 226   2011.3

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  • Bartter症候群を基盤に低K性ミオパチーの一例

    津田 玲子, 山内 理香, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   51 ( 3 )   226 - 226   2011.3

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  • Painful legs and moving toesの1例

    津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   51 ( 3 )   225 - 225   2011.3

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  • ステロイドパルスが有効であった特発性全身性無汗症の1例

    保月 隆良, 松村 晃寛, 山本 大輔, 津田 玲子, 津田 笑子, 山内 理香, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   51 ( 3 )   224 - 224   2011.3

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  • Toxin-Induced and Genetic Animal Models of Parkinson's Disease Reviewed

    Shin Hisahara, Shun Shimohama

    PARKINSONS DISEASE   2011   951709   2011

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  • Resveratrolによる神経系細胞における酸化ストレス耐性の検討

    久原 真, 齊藤 正樹, 今井 富裕, 下濱 俊

    臨床神経学   50 ( 12 )   1240 - 1240   2010.12

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  • 筋萎縮性側索硬化症(ALS)における呼吸不全の進展様式と頸髄病理所見の対応

    山内 理香, 山本 大輔, 松下 隆司, 豊島 貴信, 松村 晃寛, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊, 野中 道夫, 荻野 次郎, 外岡 暁子, 中西 勝也

    臨床神経学   50 ( 12 )   1126 - 1126   2010.12

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  • Subclinicalなneuropathyを合併した原因不明の脊髄炎の1例

    山本 大輔, 津田 笑子, 矢澤 省吾, 今井 富裕, 林 貴士, 齊藤 正樹, 久原 真, 下濱 俊

    臨床神経生理学   38 ( 5 )   331 - 331   2010.10

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  • 【意識障害 緊急を要する病状・病態の初期診療と意識障害への初期対応】神経内科でみる意識障害

    齊藤 正樹, 松村 晃寛, 津田 笑子, 久原 真

    月刊レジデント   3 ( 9 )   92 - 98   2010.9

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  • ステロイドパルス療法(IVMP)と高圧酸素療法(HBO)が奏効した間歇型一酸化炭素中毒の一例

    矢島 秀教, 豊島 貴信, 津田 笑子, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊, 文屋 尚文, 蕨 玲子, 浅井 康文

    臨床神経学   50 ( 8 )   602 - 602   2010.8

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  • 抗NMDA受容体抗体が関連したと考えられる脳炎の一例

    津田 笑子, 矢島 秀教, 豊島 貴信, 保月 隆良, 久原 真, 齊藤 正樹, 今井 富裕, 下濱 俊, 高橋 幸利

    臨床神経学   50 ( 8 )   603 - 603   2010.8

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  • 脊髄MRIで異常所見を認めた脳脊髄液減少症の一例

    佐藤 さゆり, 山本 大輔, 津田 笑子, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   50 ( 8 )   600 - 600   2010.8

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  • 左正中神経単麻痺を呈したライム病の一例

    山本 大輔, 松村 晃寛, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   50 ( 8 )   603 - 603   2010.8

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  • パーキンソン病患者の抑うつ症状と嚥下障害との関連

    韓 萌, 大西 浩文, 野中 道夫, 山内 理香, 保月 隆良, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊, 森 満

    総合リハビリテーション   38 ( 7 )   677 - 683   2010.7

  • Correlation of bite force with excitation-contraction coupling time of the masseter in myasthenia gravis Reviewed

    Emiko Tsuda, Tomihiro Imai, Takayoshi Hozuki, Rika Yamauchi, Masaki Saitoh, Shin Hisahara, Hiroaki Yoshikawa, Masakatsu Motomura, Shun Shimohama

    CLINICAL NEUROPHYSIOLOGY   121 ( 7 )   1051 - 1058   2010.7

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    Other Link: http://orcid.org/0000-0002-6350-5183

    DOI: 10.1016/j.clinph.2010.01.036

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  • ステロイドパルス療法直後の骨代謝マーカーの推移

    保月 隆良, 今井 富裕, 津田 笑子, 松村 晃寛, 山本 大輔, 山内 理香, 林 貴士, 齊藤 正樹, 久原 真, 下濱 俊

    神経治療学   27 ( 3 )   413 - 413   2010.5

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  • Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. Reviewed

    Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y

    The Journal of biological chemistry   285 ( 11 )   8375 - 8382   2010.3

  • 大量免疫グロブリン療法を施行したMPO-ANCA陽性肥厚性硬膜炎の1例

    保月 隆良, 松村 晃寛, 山本 大輔, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   50 ( 2 )   129 - 129   2010.2

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  • 3,4-diaminopyridine治療を開始した非担癌性Lambert-Eaton症候群の1例

    松村 晃寛, 松下 隆司, 保月 隆良, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    臨床神経学   50 ( 2 )   127 - 127   2010.2

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  • Response of Serum Carboxylated and Undercarboxylated Osteocalcin to Risedronate Monotherapy and Combined Therapy with Vitamin K-2 in Corticosteroid-Treated Patients: A Pilot Study Reviewed

    Takayoshi Hozuki, Tomihiro Imai, Emiko Tsuda, Akihiro Matsumura, Daisuke Yamamoto, Takanobu Toyoshima, Syuuichiro Suzuki, Rika Yamauchi, Takashi Hayashi, Shin Hisahara, Shun Shimohama

    INTERNAL MEDICINE   49 ( 5 )   371 - 376   2010

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    DOI: 10.2169/internalmedicine.49.2551

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  • 多発脳神経障害を呈する頭蓋底感染症の診断的治療について 当施設における12年間の経験から

    松村 晃寛, 津田 玲子, 山本 大輔, 豊島 貴信, 松下 隆司, 鈴木 秀一郎, 津田 笑子, 山内 理香, 保月 隆良, 林 貴士, 齊藤 正樹, 久原 真, 今井 富裕, 下濱 俊

    NEUROINFECTION   14 ( 2 )   147 - 147   2009.10

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  • Transcriptional activation of NAD+-dependent protein deacetylase SIRT1 by nuclear receptor TLX

    Naotoshi Iwahara, Shin Hisahara, Takashi Hayashi, Yoshiyuki Horio

    Biochemical and Biophysical Research Communications   386 ( 4 )   671 - 675   2009.9

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    DOI: 10.1016/j.bbrc.2009.06.103

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  • 神経・筋疾患における嚥下障害の当科治療経験例

    山本 大輔, 津田 笑子, 今井 富裕, 鈴木 秀一郎, 小田 美月, 保月 隆良, 久原 真, 野中 道夫, 山口 浩司, 金泉 悦子, 下濱 俊

    静脈経腸栄養   24 ( 3 )   849 - 849   2009.5

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  • 無菌性髄膜炎、胸腰髄病変を呈した再発性多発軟骨炎の1例

    松村 晃寛, 小田 美月, 久原 真, 野中 道夫, 今井 富裕, 下濱 俊, 荻野 次郎, 土田 哲人

    臨床神経学   49 ( 5 )   313 - 313   2009.5

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  • 原因不明のまま治療開始した頭蓋底病変の予後 多発脳神経障害を呈した感染症を中心に

    松村 晃寛, 山本 大輔, 豊島 貴信, 鈴木 秀一郎, 津田 笑子, 山内 理香, 保月 隆良, 林 貴士, 久原 真, 今井 富裕, 下濱 俊

    神経治療学   26 ( 3 )   389 - 389   2009.5

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  • 頸部放射線治療の7年後に一側性の副神経麻痺・腕神経叢障害を発症した遅発性放射線障害の1例

    松村 晃寛, 保月 隆良, 久原 真, 野中 道夫, 今井 富裕, 下濱 俊

    臨床神経学   49 ( 1 )   67 - 67   2009.1

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  • パーキンソン病患者のADLとQOLに対する抑うつの影響

    韓 萌, 大西 浩文, 森 満, 林 貴士, 久原 真, 野中 道夫, 今井 富裕, 下濱 俊

    北海道公衆衛生学雑誌   22 ( 1特別付録 )   65 - 65   2008.11

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  • Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Reviewed

    Hisahara S, Chiba S, Matsumoto H, Tanno M, Yagi H, Shimohama S, Sato M, Horio Y

    Proceedings of the National Academy of Sciences of the United States of America   105   15599 - 15604   2008.10

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  • 家族歴の判然としない遅発成人型DRPLAの1例

    松村 晃寛, 小田 美月, 久原 真, 野中 道夫, 今井 富裕, 下濱 俊

    臨床神経学   48 ( 8 )   589 - 589   2008.8

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  • Thyrotoxic myopathy mimicking myasthenic syndrome associated with thymic hyperplasia. Reviewed

    Tsuda E, Imai T, Matsumura A, Hisahara S, Nonaka M, Shiraishi H, Motomura M, Shimohama S

    Internal medicine (Tokyo, Japan)   47 ( 5 )   445 - 447   2008

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    A 41-year-old man with progressive limb weakness manifested fluctuating muscle weakness as seen in myasthenia gravis (MG). Laboratory investigations revealed hyperthyroidism without the complication of MG. Electrophysiological studies demonstrated abnormal features of neuromuscular transmissions resembling those of the Lambert-Eaton myasthenic syndrome rather than those of MG. A CT scan showed a mediastinal mass that suggested thymic hyperplasia which often complicates MG or hyperthyroidism. Medical treatment of hyperthyroidism resulted in resolution of MG-like symptoms and regression of thymic hyperplasia on CT concomitant with normalization of thyroid function. This case highlights the fact that careful investigations are needed to differentiate MG-like symptoms from genuine MG in cases of hyperthyroidism with thymic lesions.

    DOI: 10.2169/internalmedicine.47.0682

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  • 両視床の異常信号を伴う認知症を呈した硬膜動静脈瘻の1例

    松村 晃寛, 小田 美月, 保月 隆良, 野中 道夫, 久原 真, 今井 富裕, 下濱 俊, 原口 浩一, 野中 雅, 秋葉 英成

    臨床神経学   47 ( 6 )   371 - 371   2007.6

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  • 上矢状静脈洞の著明な拡張と血栓を伴った全身性エリテマトーデスの1例

    小泉 武, 大久保 由希子, 静川 裕彦, 久原 真, 野中 道夫, 今井 富裕, 千葉 進, 松本 博之, 大坂 美鈴, 宝金 清博

    臨床神経学   45 ( 1 )   61 - 61   2005.1

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  • Caspase-11 Mediates Inflammatory Dopaminergic Cell Death in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease Reviewed

    Tsuyoshi Furuya, Hideki Hayakawa, Masanori Yamada, Kenji Yoshimi, Shin Hisahara, Masayuki Miura, Yoshikuni Mizuno, Hideki Mochizuki

    Journal of Neuroscience   24 ( 8 )   1865 - 1872   2004.2

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    DOI: 10.1523/JNEUROSCI.3309-03.2004

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  • Caspases determine the vulnerability of oligodendrocytes in the ischemic brain Reviewed

    M Shibata, S Hisahara, H Hara, T Yamawaki, Y Fukuuchi, JY Yuan, H Okano, M Miura

    JOURNAL OF CLINICAL INVESTIGATION   106 ( 5 )   643 - 653   2000.9

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  • Nerve growth factor protects oligodendrocytes from tumor necrosis factor-alpha-induced injury through Akt-mediated signaling mechanisms Reviewed

    R Takano, S Hisahara, K Namikawa, H Kiyama, H Okano, M Miura

    JOURNAL OF BIOLOGICAL CHEMISTRY   275 ( 21 )   16360 - 16365   2000.5

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  • Conditional expression of anti-apoptotic protein p35 by Cre-mediated DNA recombination in cardiomyocytes from loxP-p35-transgenic mice Reviewed

    T. Araki, M. Shibata, R. Takano, S. Hisahara, S. I. Imamura, Y. Fukuuchi, T. Saruta, H. Okano, M. Miura

    Cell Death and Differentiation   7 ( 5 )   485 - 492   2000

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    DOI: 10.1038/sj.cdd.4400674

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  • Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death Reviewed

    S Hisahara, R Takano, S Shoji, H Okano, M Miura

    JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT   ( 58 )   135 - 142   2000

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  • Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death Reviewed

    S Hisahara, R Takano, S Shoji, H Okano, M Miura

    ADVANCES IN RESEARCH ON NEURODEGENERATION, VOL 7   7   135 - 142   2000

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  • Proapoptotic activity of Caenorhabditis elegans CED-4 protein in Drosophila: Implicated mechanisms for caspase activation Reviewed

    H Kanuka, S Hisahara, K Sawamoto, S Shoji, H Okano, M Miura

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   96 ( 1 )   145 - 150   1999.1

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    DOI: 10.1073/pnas.96.1.145

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  • Involvement of caspases in the TNF-alpha-mediated oligodendrocyte cell death Reviewed

    S Hisahara, S Shoji, H Okano, M Miura

    NEURAL DEVELOPMENT-BOOK   2   350 - 354   1999

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  • Involvement of caspases in cytotoxic cytokine-mediated oligodendrocyte cell death Reviewed

    M Miura, S Hisahara, R Takano, S Shoji, H Okano

    PROTOPLASMA   206 ( 4 )   219 - 223   1999

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  • Execution mechanisms of programmed cell death by caspase (ICE/CED3) family proteases Reviewed

    M Miura, S Hisahara, T Araki, H Okano

    HEART AND VESSELS   66 - 70   1997

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  • 神経筋疾患の問題症例 亜急性に進行した小脳性運動失調症と脱髄性ニューロパチーの一例

    河田 由香, 池田 和奈, 山田 稔, 齋藤 太郎, 津田 玲子, 鈴木 秀一郎, 緒方 英紀, 磯部 紀子, 久原 真

    臨床神経生理学   51 ( 5 )   508 - 508   2023.10

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  • A case presenting electrophysiological and immunological characteristics of Fisher syndrome and Lambert-Eaton myasthenic syndrome

    Kazuna Ikeda, Bungo Hirose, Daisuke Yamamoto, Shin Hisahara, Shun Shimohama, Hirokazu Shiraishi, Masakatsu Motomura, Tomihiro Imai

    Muscle and Nerve   63 ( 3 )   E16 - E18   2021.3

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    DOI: 10.1002/mus.27136

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  • 真菌・細菌性髄膜炎の1剖検例

    松浦 洋介, 津田 玲子, 山本 大輔, 松村 晃寛, 松下 隆司, 鈴木 秀一郎, 久原 真, 川又 純, 下濱 俊, 菅原 太郎, 高澤 啓

    臨床神経学   59 ( 1 )   53 - 53   2019.1

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  • 筋線維におけるMxAの高発現により診断した皮膚筋炎の1例 Reviewed

    小田 亮介, 津田 玲子, 山本 大輔, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 久原 真, 川又 純, 西野 一三, 下濱 俊

    臨床神経学   59 ( 1 )   51 - 51   2019.1

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  • アルツハイマー病モデルマウスにおける骨髄間葉系幹細胞治療のメカニズム検討

    横川和樹, 岩原直敏, 江本美穂, 久原真, 蒲生直希, 齋藤太郎, 藤倉舞, 眞部建郎, 鈴木紘美, 松下隆司, 松村晃寛, 鈴木秀一郎, 川又純, 藤井博匡, 下濱俊

    Dementia Japan   32 ( 3 )   444 - 444   2018.9

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  • APPswe/PS1dE9マウスにおけるガランタミンの超早期治療の有効性

    齋藤太郎, 久原真, 横川和樹, 蒲生直希, 藤倉舞, 眞部健郎, 岩原直敏, 松下隆司, 松村晃寛, 鈴木秀一郎, 川又純, 鈴木紘美, 江本美穂, 藤井博匡, 下濱俊

    Dementia Japan   32 ( 3 )   2018

  • 骨髄間葉系幹細胞によるアルツハイマー病治療における脳内酸化ストレス動態の検討

    横川和樹, 岩原直敏, 江本美穂, 久原真, 齋藤太郎, 藤倉舞, 眞部建郎, 鈴木紘美, 松下隆司, 松村晃寛, 鈴木秀一郎, 川又純, 藤井博匡, 下濱俊

    Dementia Japan   31 ( 4 )   564 - 564   2017.10

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  • 問題症例の神経筋電気診断 右下垂足の1例

    池田 和奈, 山本 大輔, 津田 笑子, 久原 真, 下濱 俊, 今井 富裕

    臨床神経生理学   44 ( 5 )   350 - 350   2016.10

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  • Progressive multifocal leukoencephalopathy after autologous peripheral blood stem cell transplantation in a patient with multiple myeloma treated with combination therapy

    Kazuki Yokokawa, Shin Hisahara, Yousuke Matsuura, Kazuna Ikeda, Emiko Tsuda, Masaki Saitoh, Kazuo Nakamichi, Masayuki Saijo, Yusuke Kamihara, Tsutomu Sato, Jun Kawamata, Shun Shimohama

    Journal of the Neurological Sciences   368   304 - 306   2016.9

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    DOI: 10.1016/j.jns.2016.07.045

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  • Latitude and HLA-DRB1 Alleles Affect Emergence of CSF IgG Abnormalities in MS

    Masaaki Niino, Shinya Sato, Toshiyuki Fukazawa, Satoshi Yoshimura, Shin Hisahara, Takuya Matsushita, Yuri Nakamura, Noriko Isobe, Kazuto Yoshida, Hideki Houzen, Yusei Miyazaki, Shun Shimohama, Eri Takahashi, Seiji Kikuchi, Jun-ichi Kira

    MULTIPLE SCLEROSIS JOURNAL   22 ( 3 )   406 - 406   2016.3

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  • Tolosa-Hunt症候群と鑑別が困難であった肥厚性硬膜炎の1例

    安食 さえ子, 中村 祐貴, 山田 稔, 松下 隆司, 村原 貴史, 矢澤 省吾, 林 貴士, 鈴木 秀一郎, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   948 - 948   2015.12

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  • 短期間で再増悪した脱髄性ニューロパチーの一例

    加賀 理都子, 中村 祐貴, 山田 稔, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • 嚥下障害が遷延した浸透圧性脱髄症候群の1例

    山田 稔, 村原 貴史, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • GalNAc-GD1a IgM抗体陽性急性運動感覚性軸索型ニューロパチー(AMSAN)の1例

    齋藤 太郎, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 廣瀬 文吾, 鈴木 昭治, 下濱 俊

    臨床神経学   55 ( 12 )   944 - 944   2015.12

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  • 当初cramp-fasciculation症候群を疑った運動ニューロン疾患と考えられた1例

    松浦 洋介, 村原 貴史, 倉内 麗徳, 山田 稔, 松下 隆司, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 9 )   683 - 683   2015.9

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  • 多発脳神経麻痺で発症した神経・筋サルコイドーシスの1例

    小林 未来, 廣瀬 文吾, 山本 大輔, 鈴木 秀一郎, 久原 真, 津田 笑子, 林 貴士, 齊藤 正樹, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 9 )   684 - 684   2015.9

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  • Intravenous mesenchymal stem cell administration exhibits therapeutic effects against 6-hydroxydopamine-induced dopaminergic neurodegeneration and glial activation in rats (vol 584, pg 276, 2015)

    Syuuichirou Suzuki, Jun Kawamata, Naotoshi Iwahara, Akihiro Matsumura, Shin Hisahara, Takashi Matsushita, Masanori Sasaki, Osamu Honmou, Shun Shimohama

    NEUROSCIENCE LETTERS   587   5 - 5   2015.2

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  • SCA3における末梢神経障害の電気生理学的検討

    廣瀬 文吾, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 林 貴士, 斎藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   55 ( 2 )   131 - 131   2015.2

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  • 皮疹を伴わず髄液検査にてVZV‐PCR陽性であった無菌性髄膜炎の1例

    小林未来, 津田笑子, 鈴木秀一郎, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 今井富裕

    臨床神経学   54 ( 1 )   87 - 87   2014.1

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  • フィンゴリモド導入前のスクリーニング検査にて心機能低下を認めた多発性硬化症の1例

    齋藤太郎, 岩原直敏, 山本大輔, 山内理香, 久原真, 齊藤正樹, 川又純, 下濱俊

    臨床神経学   54 ( 1 )   91 - 91   2014.1

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  • 診断に苦慮した複合性局所性疼痛症候群の1例

    外山祐一郎, 田中真理子, 山本大輔, 鈴木秀一郎, 津田笑子, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   54 ( 1 )   91 - 91   2014.1

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  • 眼瞼下垂,複視,球症状を呈し,重症筋無力症と鑑別を要した眼咽頭型筋ジストロフィー(OPMD)の1例

    藤倉舞, 山本大輔, 津田笑子, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   54 ( 1 )   90 - 90   2014.1

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  • 再発性多発脳出血を呈した原発性中枢神経限局性血管炎(PACNS)の1例

    越智龍太郎, 中村祐貴, 小林未来, 津田笑子, 齊藤正樹, 馬場雄大, 高桑康成, 鈴木秀一郎, 林貴士, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   54 ( 1 )   89 - 89   2014.1

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  • 感覚障害と失調を認めたギランバレー症候群特殊病型の1例

    池田和奈, 村原貴史, 津田笑子, 鈴木秀一郎, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 今井富裕

    臨床神経学   54 ( 1 )   88 - 88   2014.1

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  • パーキンソン病モデルラットにおけるヒト骨髄間葉系幹細胞の静脈投与の有効性について

    鈴木秀一郎, 鈴木紘美, 山内綾乃, 岩原直敏, 松村晃寛, 久原真, 川又純, 下濱俊

    日本神経学会学術大会プログラム・抄録集   55th   653   2014

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  • 電子常磁性共鳴法を用いたアルツハイマー病モデル動物における脳内酸化ストレスの解析

    松村晃寛, 鈴木紘美, 山内綾乃, 岩原直敏, 鈴木秀一郎, 久原真, 川又純, 江本美穂, 藤井博匡, 下濱俊

    日本神経学会学術大会プログラム・抄録集   55th ( Suppl. )   722 - S235   2014

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  • マウス初代培養ミクログリアにおけるアセチルコリンおよびグルタミン酸受容体の発現

    岩原直敏, 山内綾乃, 鈴木紘美, 松村晃寛, 鈴木秀一郎, 久原真, 川又純, 下濱俊

    日本神経学会学術大会プログラム・抄録集   55th   723   2014

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  • 培養オリゴデンドロサイト形態における脱アセチル化酵素SIRTの関与

    久原真, 岩原直敏, 鈴木秀一郎, 松村晃寛, 林貴士, 齊藤正樹, 川又純, 下濱俊

    日本神経学会学術大会プログラム・抄録集   55th ( Suppl. )   737 - S250   2014

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  • 脱アセチル化酵素SIRTの培養オリゴデンドロサイト分化制御における関与の検討

    久原 真, 鈴木 秀一郎, 松村 晃寛, 林 貴士, 齊藤 正樹, 川又 純, 今井 富裕, 下濱 俊

    臨床神経学   53 ( 12 )   1571 - 1571   2013.12

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  • アルツハイマー病トランスジェニックモデルマウスにおける脳内グリア細胞の動態解析

    松村 晃寛, 鈴木 紘美, 大橋 乃理子, 鈴木 秀一郎, 山内 理香, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊, 佐々木 祐典, 本望 修, 三國 信啓, 高田 和幸, 北村 佳久

    臨床神経学   53 ( 12 )   1483 - 1483   2013.12

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  • 脳卒中様発作の発症初期にL‐アルギニン製剤静注が著効したA3243G変異MELAS男性例

    藤倉舞, 越智龍太郎, 外山祐一郎, 岩原直敏, 津田笑子, 齊藤正樹, 久原真, 川又純, 下濱俊

    神経治療学   30 ( 5 )   641 - 641   2013.9

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  • 多発性硬化症(MS)の経過中に慢性炎症性脱髄性多発根神経炎(CIDP)を合併した1例

    齋藤太郎, 越智龍太郎, 山本大輔, 松村晃寛, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   53 ( 7 )   586 - 586   2013.7

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  • III型クリオグロブリン血症に伴う多発単神経炎の1例

    山本大輔, 今井富裕, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊

    臨床神経学   53 ( 7 )   588 - 588   2013.7

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  • 軽微な筋症状と急速進行性の間質性肺炎のため救命し得なかった皮膚筋炎の一例

    津田玲子, 保月隆良, 齊藤正樹, 久原真, 今井富裕, 川又純, 下濱俊

    臨床神経学   53 ( 4 )   321 - 321   2013.4

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  • C型慢性肝炎に対するPEG‐IFN α2a/ribavirin併用療法中に発症したNMO(neuromyelitis optica)の1例

    津田笑子, 津田玲子, 久原真, 山内理香, 林貴士, 齊藤正樹, 川又純, 今井富裕, 下濱俊, 佐賀啓良

    臨床神経学   53 ( 4 )   320 - 320   2013.4

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  • 抗ガングリオシド抗体を認め頚髄および末梢神経に異常所見を呈した一例

    岩原直敏, 津田玲子, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   53 ( 4 )   323 - 323   2013.4

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  • Lambert‐Eaton症候群に多発ニューロパチーを合併した腫瘍随伴症候群の1例

    外山祐一郎, 津田玲子, 岩原直敏, 津田笑子, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   53 ( 4 )   321 - 321   2013.4

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  • 脱アセチル化酵素SIRTの培養オリゴデンドロサイト分化制御における関与の検討

    久原真, 鈴木秀一郎, 松村晃寛, 林貴士, 齊藤正樹, 川又純, 今井富裕, 下濱俊

    日本神経学会学術大会プログラム・抄録集   54th   462   2013

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  • アルツハイマー病トランスジェニックモデルマウスにおける脳内グリア細胞の動態解析

    松村晃寛, 鈴木紘美, 大橋乃理子, 鈴木秀一郎, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 佐々木祐典, 本望修, 三國信啓, 高田和幸, 北村佳久

    日本神経学会学術大会プログラム・抄録集   54th   369   2013

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  • PS1遺伝子同一アリル上に隣接する新規点変異と欠失を認めた家族性AD家系

    川又純, 小林清樹, 津田玲子, 鈴木秀一郎, 松村晃寛, 津田笑子, 久原真, 下濱俊

    日本神経学会学術大会プログラム・抄録集   54th   308   2013

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  • パーキンソン病モデルラットに対するα7ニコチン性受容体作動薬による神経保護作用

    鈴木秀一郎, 鈴木紘美, 大橋乃理子, 松村晃寛, 久原真, 川又純, 下濱俊, 高田和幸, 北村佳久

    日本神経学会学術大会プログラム・抄録集   54th   448   2013

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  • Pure autonomic neuropathyの臨床病理学的特徴

    小池 春樹, 橋本 里奈, 冨田 稔, 川頭 祐一, 飯島 正博, 児矢野 繁, 桃尾 隆之, 湯浅 浩之, 三竹 重久, 東原 真奈, 海田 賢一, 山本 大輔, 久原 真, 下濱 俊, 中江 啓晴, 城倉 健, 祖父江 元

    末梢神経   23 ( 2 )   252 - 253   2012.12

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  • 脳内アミロイドβに対する脳内グリア細胞の動態解析

    松村 晃寛, 鈴木 紘美, 松下 隆司, 鈴木 秀一郎, 林 貴士, 保月 隆良, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊, 本望 修, 高田 和幸, 北村 佳久

    臨床神経学   52 ( 12 )   1582 - 1582   2012.12

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  • 高齢者を対象とした末梢神経伝導検査の問題点

    今井富裕, 津田笑子, 山内理香, 保月隆良, 齊藤正樹, 久原真, 川又純, 下濱俊

    日本老年医学会雑誌   49 ( 6 )   807 - 807   2012.11

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  • 幼児期より繰り返す病歴を有する外転神経麻痺を呈した眼筋麻痺性片頭痛の一例

    越智龍太郎, 山内理香, 久原真, 橋本雅人, 保月隆良, 林貴士, 齊藤正樹, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 6 )   460 - 460   2012.6

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  • 首下がりの1症例

    外山祐一郎, 山内理香, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 6 )   457 - 457   2012.6

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  • 平山病が疑われた肘部尺骨神経障害の1例

    津田笑子, 今井富裕, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 射場浩介, 静川裕彦

    臨床神経学   52 ( 6 )   457 - 457   2012.6

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  • 右眼瞼下垂と眼球運動障害を認めた巨細胞性動脈炎の1例

    津田玲子, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 6 )   456 - 456   2012.6

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  • 中枢性顔面神経麻痺に対側末梢性顔面神経麻が加わった1症例

    山内理香, 岩原直敏, 津田玲子, 津田笑子, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 6 )   458 - 458   2012.6

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  • 骨硬化像を有する血液疾患が併存した慢性炎症性多発ニューロパチーの1例

    保月隆良, 津田笑子, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 3 )   202 - 202   2012.3

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  • 診断確定の6ケ月後からに下肢筋力低下と多発脳神経症状が出現した神経サルコイドーシスの1例

    保月隆良, 岩原直敏, 津田笑子, 山内理香, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 3 )   200 - 200   2012.3

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  • 抗VGKC抗体陽性非ヘルペス性辺縁系脳炎の2例―抗LGI1抗体の検討―

    津田玲子, 津田笑子, 山内理香, 久原真, 川又純, 今井富裕, 下濱俊, 山本大輔

    臨床神経学   52 ( 3 )   198   2012.3

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  • 進行性筋萎縮症(PMA)の1剖検例における異常TDP‐43

    山内理香, 山本大輔, 岩原直敏, 津田玲子, 松村晃寛, 鈴木秀一郎, 津田笑子, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 杉本幸太郎, 一宮慎吾, 長谷川匡

    臨床神経学   52 ( 3 )   199 - 199   2012.3

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  • Girdle sensationを呈したGuillain‐Barre症候群の1例

    岩原直敏, 山口鮎美, 津田笑子, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   52 ( 3 )   202 - 202   2012.3

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  • パーキンソン病モデルラットに対する選択的ニコチン受容体作動薬による中脳黒質領域の免疫組織学的解析

    鈴木秀一郎, 鈴木紘美, 松村晃寛, 松下隆司, 久原真, 川又純, 下濱俊, 高田和幸, 北村佳久, 谷口隆之

    日本神経学会学術大会プログラム・抄録集   53rd   430   2012

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  • 脳内アミロイドβに対する脳内グリア細胞の動態解析

    松村晃寛, 鈴木紘美, 松下隆司, 鈴木秀一郎, 林貴士, 保月隆良, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊, 本望修, 高田和幸, 北村佳久

    日本神経学会学術大会プログラム・抄録集   53rd   423   2012

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  • 呼吸不全の進行と横隔神経複合筋活動電位の低下が相関しないALSの臨床的特徴

    山内理香, 今井富裕, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊

    日本神経学会学術大会プログラム・抄録集   53rd   448   2012

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  • 重症筋無力症(MG)と初期診断され,その後特異な臨床経過をとった担癌性Lambert‐Eaton症候群の1例

    保月隆良, 津田笑子, 松村晃寛, 山内理香, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経生理学   39 ( 5 )   454 - 454   2011.10

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  • 右視床梗塞に関連すると思われた左上肢不随意運動の1例

    松村晃寛, 保月隆良, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   51 ( 6 )   455 - 455   2011.6

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  • Lambert‐Eaton症候群(LEMS)の診断から4年後に膵癌を発症した1例.

    保月隆良, 松村晃寛, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    臨床神経学   51 ( 6 )   456 - 456   2011.6

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  • 腰仙部硬膜外脂肪腫症の1例

    津田笑子, 今井富裕, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 山本大輔

    臨床神経学   51 ( 6 )   455 - 455   2011.6

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  • パーキンソン病患者の抑うつ症状と摂食・嚥下障害との関連―3年間の結果のまとめ―

    大西浩文, 韓萌, 森満, 野中道夫, 千葉進, 山内理香, 保月隆良, 林貴士, 久原真, 今井富裕, 下濱俊

    特定疾患の疫学に関する研究 平成22年度 総括・分担研究報告書   313 - 320   2011

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  • 筋萎縮性側索硬化症における鼻腔吸気圧測定:『開放法』と『閉鎖法』

    山内理香, 山本大輔, 松村晃寛, 津田笑子, 保月隆良, 林貴士, 齊藤正樹, 久原真, 川又純, 今井富裕, 下濱俊

    日本神経学会学術大会プログラム・抄録集   52nd   433   2011

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  • 赤血球画分を用いた酸化DJ‐1定量の検討

    松村晃寛, 久原真, 齊藤正樹, 川又純, 今井富裕, 下濱俊, 斎藤芳郎, 野口範子, 二木鋭雄

    日本神経学会学術大会プログラム・抄録集   52nd   329   2011

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  • 咬筋のend‐plateは生理的刺激頻度では伝達ブロックが起きにくい

    今井富裕, 津田笑子, 山内理香, 保月隆良, 齊藤正樹, 久原真, 川又純, 下濱俊

    日本神経学会学術大会プログラム・抄録集   52nd   533   2011

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  • 抗リアノジン受容体抗体陽性重症筋無力症患者の臨床的特徴

    津田 笑子, 今井 富裕, 保月 隆良, 林 貴士, 齊藤 正樹, 久原 真, 下濱 俊, 吉川 弘明, 本村 政勝

    臨床神経学   50 ( 12 )   1138 - 1138   2010.12

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  • パーキンソン病患者のQOLに対する抑うつの影響

    HAN Meng, 大西浩文, 野中道夫, 山内理香, 保月隆良, 林貴士, 齊藤正樹, 久原真, 今井富裕, 矢澤省吾, 坂内文男, 下濱俊, 千葉進, 森満

    北海道公衆衛生学雑誌   23 ( 2 )   96 - 102   2010.3

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  • 神経変性疾患の治療法の現状と問題点

    下濱俊, 川又純, 久原真

    生体機能と創薬シンポジウム要旨集   2010   16   2010

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  • 運動症状の重症度とは独立して,抑うつ症状の重症度がパーキンソン病患者の嚥下障害と関連した

    韓萌, 大西浩文, 野中道夫, 山内理香, 保月隆良, 林貴士, 久原真, 今井富裕, 下濱俊, 森満

    日本摂食嚥下リハビリテーション学会雑誌   13 ( 3 )   332 - 333   2009.12

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  • パーキンソン病患者の抑うつ症状と摂食・嚥下障害について―札幌医大神経内科外来連続症例での検討―

    韓萌, 大西浩文, 森満, 野中道夫, 山内理香, 保月隆良, 林貴士, 久原真, 斉藤正樹, 今井富裕, 下濱俊

    北海道公衆衛生学雑誌   23 ( 1 )   99   2009.11

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  • Expression of subforms of NAD(+)-dependent histone deacetylase SIRT3 in the brain

    Takashi Hayashi, Shin Hisahara, Shun Shimohama, Yoshiyuki Horio

    NEUROSCIENCE RESEARCH   65   S164 - S164   2009

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    DOI: 10.1016/j.neures.2009.09.851

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  • 重症筋無力症における咬筋興奮収縮連関と抗ryanodine受容体抗体の関連について

    津田 笑子, 今井 富裕, 保月 隆良, 久原 真, 野中 道夫, 下濱 俊, 丸田 高広, 吉川 弘明

    臨床神経学   48 ( 12 )   1224 - 1224   2008.12

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    Ichushi

    J-GLOBAL

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  • MXA expression in multiple sclerosis

    Hiroyasu Furuyama, Susumu Chiba, Tamaki Okabayashi, Shin-ichi Yokota, Michio Nonaka, Shin Hisahara, Tomihiro Imai, Tateo Warabi, Nobuhiro Fujii, Shun Shimohama

    JOURNAL OF NEUROIMMUNOLOGY   203 ( 2 )   127 - 127   2008.10

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  • Expression of subforms of NAD(+)-dependent histone deacetylase SIRT3 in the brain

    Takashi Hayashi, Shin Hisahara, Yoshinobu Nagaoka, Shun Shimohama, Yoshiyuki Horio

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   161P - 161P   2008

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  • NAD-dependent histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation

    Shin Hisahara, Susumu Chiba, Hiroyuki Matsumoto, Masaya Tanno, Shun Shimohama, Makoto Sato, Yoshiyuki Horio

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   114P - 114P   2008

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  • 2.片側多小脳回の成人例にみられたmirror movementのリハビリテーション経験(第16回日本リハビリテーション医学会北海道地方会)

    有吉 直充, 津田 笑子, 久原 真, 野中 道夫, 今井 富裕, 下濱 俊, 村上 孝徳, 石合 純夫

    リハビリテーション医学 : 日本リハビリテーション医学会誌   44 ( 10 )   620 - 621   2007.10

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  • Nuclear translocation of histone deacetylase SIRT1 affects neuronal differentiation

    Shin Hisahara, Susumu Chiba, Hiroyuki Matsumoto, Makoto Sato, Shun Shimohma, Yoshiyuki Horio

    NEUROSCIENCE RESEARCH   58   S32 - S32   2007

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  • Functions of histone deacetylase SIRT1 in neural differentiation

    Shin Hisahara, Susumu Chiba, Hiroyuki Matsumoto, Yoshiyuki Horio

    NEUROSCIENCE RESEARCH   55   S144 - S144   2006

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  • Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2α)

    HISAHARA S

    J Pharmacol Sci   98   200 - 204   2005

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  • Introduction of current research activities in neurology department

    Hiroyuki Matsumoto, Susumu Chiba, Tomihiro Imai, Michio Nonaka, Shin Hisahara

    Sapporo Medical Journal   73 ( 4-6 )   27 - 30   2004.12

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    Language:Japanese   Publishing type:Book review, literature introduction, etc.  

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  • Caspase-mediated oligodendrocyte cell death in the pathogenesis of autoimmune demyelination

    S Hisahara, H Okano, M Miura

    NEUROSCIENCE RESEARCH   46 ( 4 )   387 - 397   2003.8

  • Functional analysis of SIR2

    Yoshiyuki Horio, Shin Hisahara, Jun Sakamoto

    Folia Pharmacologica Japonica   122 ( 1 )   30 - 32   2003

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    PubMed

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  • Molecular analysis of aging; NAD dependent histone deacetylase, SIR2

    Yoshiyuki Horio, Jun Sakamoto, Shin Hisahara

    Sapporo Medical Journal   71 ( 3-4 )   13 - 18   2002.8

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  • Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination

    S Hisahara, JY Yuan, T Momoi, H Okano, M Miura

    JOURNAL OF EXPERIMENTAL MEDICINE   193 ( 1 )   111 - 122   2001.1

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  • Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination

    S Hisahara, T Araki, F Sugiyama, K Yagami, M Suzuki, K Abe, K Yamamura, J Miyazaki, T Momoi, T Saruta, CCA Bernard, H Okano, M Miura

    EMBO JOURNAL   19 ( 3 )   341 - 348   2000.2

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  • Effects of neurotrophins in TNF induced oligodendrocyte cell death

    TAKANO R., HISAHARA S., OKANO H., MIURA M.

    21   568 - 568   1998.12

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  • Caenorhabditis elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells

    S Hisahara, H Kanuka, S Shoji, S Yoshikawa, H Okano, M Miura

    JOURNAL OF CELL SCIENCE   111   667 - 673   1998.3

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  • ICE/CED-3 family executes oligodendrocyte apoptosis by tumor necrosis factor

    S Hisahara, S Shoji, H Okano, M Miura

    JOURNAL OF NEUROCHEMISTRY   69 ( 1 )   10 - 20   1997.7

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Awards

  • 年会ポスター優秀賞

    2003.3   日本薬理学会  

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  • 日本神経科学学会奨励賞

    2002.7  

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Research Projects

  • Role of microglia-derived exosomes in the neurodegeneration of multiple sclerosis.

    Grant number:23K06967  2023.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • 周皮細胞のアルツハイマー病モデルにおける分化転換の解析

    Grant number:22K07541  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    久原 真

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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  • Analysis of microRNA in oligodendrocyte degeneration

    Grant number:17K07099  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hisahara Shin

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    We successfully established collect oligodendrocyte premature cells (OPC) in the primary culture from mouse embryonic brain, however, it was difficult to identify significant miRNA derived from differentiating OPCs. So we modified our strategy, showing the function of SIRTs in the OPC differentiation. Knockdown of not only SIRT1 but also SIRT2 promoted increasing number of well-differentiated OLGs. The mature OLGs show broadly cellular distribution of OLG-specific cytoskeleton-related molecules, βIV-tubulin and tubulin polymerization promoting protein (TPPP). Although βIV-tubulin and TPPP are not directly associated with SIRT1/SIRT2, we demonstrated that knockdown of SIRT1 and SIRT2 independently give rise to induction of these molecules. Our findings indicate that SIRT1 and SIRT2 inhibitory regulate OLG differentiation, at least from OLG progenitor cells, through the suppression of expression of OLG-specific cytoskeleton-related molecules and their subcellular distribution.

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  • Functional analysis of histone deacetylase SIRT in the pathophysiology of neurodegenerative disorders

    Grant number:21591096  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HISAHARA Shin, SHIMOHAMA Shun

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    We now have investigating the function of histone deacetylase SIRT(sirtuin). To explore preventive effect against cell death, we have performed cell viability assay in PC12 and SHSY5Y cells with administration of hydrogen peroxide(H2O2) and 6-hydroxydopamine(6-OHDA). Administration of resveratrol, an activator of SIRT, and overexpression of SIRT1 resulted in significant inhibition of oxidative stress-induced cell death. We also found that overexpression of SIRT1H355Y, a dominant-negative SIRT1, showed partial inhibition of cell death. These results indicate that SIRT1 promotes cellular viability via deacetylase activity-dependent and -independent mechanisms.

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  • 神経細胞増殖・分化におけるヒストン脱アセチル化酵素Sirの役割

    Grant number:15700261  2003 - 2004

    日本学術振興会  科学研究費助成事業  若手研究(B)

    久原 真

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    Grant amount:\3600000 ( Direct Cost: \3600000 )

    1)ヒストン脱アセチル化酵素Sir2α(SIRT1)の中枢神経系における発現
    成体マウス中枢神経における発現細胞の同定を行うため免疫染色を試みた。SIRT1は側脳室のsubventricular zone(SVZ)に発現が豊富でnestin陽性細胞でも発現していることから神経幹細胞を含む未分化神経系細胞である可能性があった。そこでさらに各種マーカーとの多重染色を試みSVZ領域のtype B, C, A細胞と上衣細胞に発現していることが明らかとなった。SIRT1はrostral migratory stream(RMS)や嗅球におけるPSA-NCAM陽性細胞や海馬歯状核のnestin陽性細胞には発現が無くSVZ周辺の未分化細胞に限局した発現と考えられた。
    2)Neurosphere assayにおけるSIRT1機能の解析
    胎生14日目の胎児脳から線条体組織を培養して実験を行った。培地中にSIRT1の阻害剤であるnicotinamide, splitomicin, sirtinolなどを培地に投与するとneurosphereの成長が阻害されたが非投与群に対して細胞死の割合は増加していなかった。またこれらのsphereを血清を含んだ培地に移し人為的にneuron, oligodendrocyte, astrocyteへ分化させる際にこれらの阻害剤を投与する実験も行った。その結果阻害剤投与でneuron, oligodendrocyteを含有したneurosphereが著明に減少した。これらよりSIRT1が神経幹細胞の増殖や分化に重要な役割を果たすと考えられた。

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  • 老化と体内時計

    Grant number:15659062  2003 - 2004

    日本学術振興会  科学研究費助成事業  萌芽研究

    堀尾 嘉幸, 八田 愼一, 坂本 淳, 久原 真

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    Sir2は酵母で発見された転写抑制因子で性遺伝子、rRNA領域、テロメア領域の発現を抑制するNAD依存性蛋白質脱アセチル化酵素である。Sir2の過剰発現によって酵母と線虫の寿命が延長することから注目されている。カロリー制限は酵母から高等動物までただ1つの寿命延長をもたらす方法であるが、酵母ではカロリー制限による寿命延長作用にSir2が必要であることが示されている。我々はマウスをモデルとしてSir2ファミリーに1つのSIRT1(Sir2α)が神経幹細胞などの未分化幼弱細胞に強く発現していることを見出した。Sir2αの発現は胎生4.5日から強く見られ、胎生18.5日まで1日ごとにしだいに減少していた。また、脊髄等の神経細胞、心臓に胎生期では強い発現が見られた。神経幹細胞の一次培養細胞を用いて、Sir2αが神経幹細胞に強く発現し、幹細胞を血清添加によって分化させるとその発現が消失すること、Sir2αの阻害薬のニコチンアミドやサーチノールを添加すると幹細胞の増殖が停止し、その停止は細胞周期のG2/M期の細胞が減少するため、即ち、分裂が止まるためであることを見出した。これはSir2αが幹細胞の分裂に関与するという初めての知見である。また、Sir2α阻害薬は神経幹細胞の神経への分化を抑制することも見出した。一方、アストロサイトへの分化は阻害されなかった。Sir2αに結合する蛋白質をSir2αのGST融合蛋白質を用いて検討し、脳からはDDX1というRNA helicase、肝臓からはaldolaseが分離精製された。これらの意義について検討している。一方、精巣のSir2αの発現について検討し、Sir2αは最も未分化な精粗細胞には発現せず、精母細胞に強く、初期分化段階の精子細胞に弱く発現した。Sir2αを発現する細胞はNotch1の細胞内ドメインが核に検出された。その意義を検討している。

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  • 脳Sirの老化、寿命における分子機能解析

    Grant number:13035038  2001 - 2002

    日本学術振興会  科学研究費助成事業  特定領域研究

    堀尾 嘉幸, 坂本 淳, 竹村 晴夫, 八田 愼一, 久原 真, 宮本 篤

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    Grant amount:\7500000 ( Direct Cost: \7500000 )

    NAD依存性ヒストン脱アセチル化酵素SIR2ファミリーの高等動物における生理的機能、特に老化や寿命との関連を調べるためにマウス脳cDNAライブラリーより、SIR2αとSIR3 cDNAをクローン化した。SIR2αは1種類、SIR3は4種類のdifferential splicing産物と考えられるクローンが単離された。分布をNorthern blotおよび、それぞれの抗体を作成しWestern blotによって検討し、SIR2αは脳、心臓、精巣などに、また、SIR3は全身の臓器に発現していた。発生過程の発現量をNorthern blotで調べたところ、両者とも胎児に多量の発現を認めた。そこで、SIR2αについてさらに詳細に検討をおこなった。BrdUを飲水にとかし、2週間もしくは3週間マウスに連続投与したあと、1週間後にその脳を取り出し免疫組織化学法で分裂する脳神経幹細胞をラベルしたところ、神経幹細胞にSIR2αの多量の発現が見られた。さらに、胎生13.5日のマウス脳から単離し培養した神経幹細胞は増殖して球状のneurosphereを形成するが、このneurosphereを形成する細胞にSIR2αの多量発現が見られた。この発現はneurosphereを血清を含む分化条件にさらすと速やかに消失した。これとは別に、精巣のSIR2αの発現も精子の幹細胞である精粗細胞に強い発現が見られた。したがって、SIR2αは神経などの幹細胞において何らかの役割を果たしている可能性がきわめて高いことが判明した。
    一方、SIR2αは神経幹細胞では核と細胞質に発現していた。そこで、この局在機構を調べるために各種deletion mutantsを作成しそれぞれにGFPを結合させたものをCOS細胞に発現させて細胞内局在を調べた。SIR2αには2つの核局在配列が存在するが、この両者とも活性を持っていること、核局在配列の塩基性アミノ酸をアラニンに置換したものではその活性が失われることを明らかとした。

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  • Mechanism of water transport; Elucidation of brain edema and development of treatment.

    Grant number:12557232  2000 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    HORIO Yoshiyuki, SAKAMOTO Jun, TAKEMURA Haruo, HATTA Shinnichi, INUZUKA Eiji, HISAKARA Shin

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    Grant amount:\13100000 ( Direct Cost: \13100000 )

    We have studied the distribution of AQP4 water channel in Muller cells, dominant glial cells of the retina, using primary culture of Muller cells. When the cells were cultured on poly lysine-coated glass, AQP4 located in the cytoplasm. We could not find any expression of AQP4 on the membranes. However, when Muller cells were planted on laminine-coated glass, AQP4 was found on the membranes. Expression of AQP4 on the membranes of Muller cells disappeared in the presence of Herbimycin, a thyrosine kinase inhibitor. Extracellular matrix regulates water channel expression on the membranes through the function of a tyrosine kinase. Thus, brain damage causing functional disorder of extracellular matrix may affect surface expression of AQP4 and induce unbalance of water. transport.
    Water transport is accompanied with ion transport. Previous experiment showed K^+ channels are important for water transport. We have studied ATP sensitive K^+ channels(KATP channels), because KATP channels open when cells have damage. We found that KATP channels expressed in neurons. Expression of subfamily of KATP channels was different in a neuron. We found that SUR1 subunit existed in the cell body, while SUR2 subunit located in terminals of neuritis. The difference of expression may indicate functional difference of KATP channel subunit.

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  • Investigation for the roles of ions in the differentiation, structure and death in cells

    Grant number:12470021  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    HORIO Yoshiyuk, TAKEMURA Haruo, HATTA Shinnichi, MIYAMOTO Atsushi, HISAKARA Shin, SAKAMOTO Jun

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    Grant amount:\4500000 ( Direct Cost: \4500000 )

    We have made specific antibodies against sulfonylurea receptor (SUR) subunits of ATP sensitive K^+ channels (KATP channels) and also made antibody against Kir6.2 subunit of KATP channels. There are one and three sub forms of SUR1 and SUR2 subunits, respectively. Our antibodies could recognize each of these SUR subunits. Using brain slices and PC12 cells, we found that SUR2 is expressed in the terminal regions of neurites of neurons, while SUR1 subunit is expressed in the cell bodies. Moreover, we found that SUR2B is expressed in the hippocampus CA3 regions. Immunoreactivity of SUR2B is detected terminals of mossy fibers, reflected from granular neurons of dentate gyms. Previously, it is reported that dopamine neurons of Weaver mouse, a model mouse of Parkinson disease, died gradually, but subpopulation of dopamine neurons in substantia nigra survived. The survived neurons expressed KATP channels containing SUR1. The reason of survival can be explained by the cell body expression of KATP channels containing SUR1. Thus, KATP channels might be one of molecules to prevent cell death.

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  • 脱髄疾患時のオリゴデンドロサイト細胞死とカスパーゼファミリー活性化機序の解析

    Grant number:98J06871  1998 - 1999

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    久原 真

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    Grant amount:\1800000 ( Direct Cost: \1800000 )

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  • 神経幹細胞の増殖・分化に影響する分子の機能解析

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    Grant type:Competitive

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  • 脱髄疾患病態生理におけるオリゴデンドロサイトの分子動態の検討

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    Grant type:Competitive

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