中原 仁 (ナカハラ ジン)

NAKAHARA Jin

写真a

所属(所属キャンパス)

医学部 内科学教室(神経) Department of Neurology, Keio University School of Medicine (信濃町)

職名

教授

メールアドレス

メールアドレス

HP

外部リンク

プロフィール 【 表示 / 非表示

  • ・日本神経学会
      関東甲信越支部代表
      代議員
      英文誌編集委員会幹事
      将来構想委員会委員
      年次学術委員(第61回)
    ・日本内科学会
      評議員
    ・日本神経免疫学会
      理事
    ・日本神経治療学会
      評議員
    ・日本神経感染症学会
      評議員
    ・日本多発性硬化症ネットワーク
      理事
    ・環アジア多発性硬化症治療研究会議(PACTRIMS)
      中央委員会委員

教員からのメッセージ 【 表示 / 非表示

  • 神経内科領域のあらゆる疾患を対象に、先進的なトランスレーショナル・リサーチから在宅医療まで、手段を問わず患者の生命の質(quality of life)を改善させる治療の具現化に向けた研究を行っている。

その他の所属・職名 【 表示 / 非表示

  • グローバルリサーチインスティテュート, 副所長

経歴 【 表示 / 非表示

  • 2003年04月
    -
    2004年03月

    慶應義塾大学, COEプログラム(生命科学), 研究員

  • 2004年04月
    -
    2007年03月

    独立行政法人日本学術振興会, 特別研究員(DC1)

  • 2007年04月
    -
    2008年11月

    独立行政法人日本学術振興会, 特別研究員(PD)

  • 2008年12月
    -
    2013年03月

    慶應義塾大学, 医学部総合医科学研究センター, 特任講師

  • 2013年04月
    -
    2018年03月

    慶應義塾大学, 医学部内科学教室(神経), 助教

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学歴 【 表示 / 非表示

  • 2003年03月

    慶應義塾, 医学部

    大学, 卒業

  • 2007年03月

    慶應義塾, 医学研究科, 生理系専攻

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾, 課程, 2007年03月

免許・資格 【 表示 / 非表示

  • 医師免許証, 2003年05月

  • 日本医師会認定産業医, 2011年09月

  • 日本内科学会認定内科医, 2013年09月

  • 日本神経学会認定神経内科専門医, 2014年07月

 

研究分野 【 表示 / 非表示

  • 神経内科学

研究キーワード 【 表示 / 非表示

  • オリゴデンドロサイト

  • 多発性硬化症

  • 神経免疫学

  • 神経内科学

  • 視神経脊髄炎関連疾患

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研究テーマ 【 表示 / 非表示

  • 神経治療学の拠点形成, 

    2018年
    -
    継続中

  • 多発性硬化症の臨床研究, 

    2011年
    -
    継続中

  • 中枢神経系髄鞘再生療法の開発, 

    1999年
    -
    継続中

 

論文 【 表示 / 非表示

  • Cytometric cell-based assays for anti-striational antibodies in myasthenia gravis with myositis and/or myocarditis

    Kufukihara K., Watanabe Y., Inagaki T., Takamatsu K., Nakane S., Nakahara J., Ando Y., Suzuki S.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019年12月

     概要を見る

    © 2019, The Author(s). The purposes of the present study were to identify anti-striational antibodies in myasthenia gravis (MG) patients with myositis and/or myocarditis using a combination of cell-based assays and flow cytometry (cytometric cell-based assays) and to describe the main clinical implications. Among 2,609 stored samples collected from all over Japan between 2003 and 2016, we had serum samples from 30 MG patients with myositis and/or myocarditis. Cytometric cell-based assays with titin, ryanodine receptor, and voltage-gated Kv1.4 were performed. Autoantibodies were determined by differences in phycoerythin fluorescence between the 293F cells and titin-transfected cells. MG patients with myositis and/or myocarditis as well as late-onset and thymoma-associated MG had anti-titin, anti-ryanodine receptor, and anti-Kv1.4 antibodies. In contrast, patients with early-onset MG, those with other myopathies and healthy controls did not have anti-titin or anti-Kv1.4 antibodies with some exceptions, but they possessed anti-ryanodine receptor antibodies. Thirty MG patients with myositis and/or myocarditis showed a severe generalized form, and 21 of them had thymoma. Anti-titin and anti-Kv1.4 antibodies were found in 28 (93%) and 15 (50%) patients, respectively, and all patients had at least one of these antibodies. Cytometric cell-based assays thus demonstrated that anti-striational antibodies are biomarkers of MG with myositis and/or myocarditis.

  • Inflammatory myopathy associated with PD-1 inhibitors

    Seki M., Uruha A., Ohnuki Y., Kamada S., Noda T., Onda A., Ohira M., Isami A., Hiramatsu S., Hibino M., Nakane S., Noda S., Yutani S., Hanazono A., Yaguchi H., Takao M., Shiina T., Katsuno M., Nakahara J., Matsubara S., Nishino I., Suzuki S.

    Journal of Autoimmunity (Journal of Autoimmunity)  100   105 - 113 2019年06月

    ISSN  08968411

     概要を見る

    © 2019 Elsevier Ltd Objective: To characterize the inflammatory myopathy associated with programmed cell death 1 inhibitors (PD-1 myopathy). Methods: We studied 19 Japanese patients with PD-1 myopathy (13 men and 6 women, mean age 70 years), who were referred to Keio University. As control groups, we used 68 patients with anti-signal recognition particle antibodies, 51 patients with anti-aminoacyl transfer RNA synthetase antibodies and 460 healthy subjects. Results: In regard to muscle-disease severity, 10 patients showed a mild form of disease and 9 patients showed a severe form. Non-small cell lung cancer was the most common underlying cancer. PD-1 inhibitor consisted of 11 nivolumab and 8 pembrolizumab. PD-1 myopathy occurred 29 days on average after the first administration of PD-1 inhibitor. The initial manifestation of muscle weakness was ptosis in 10 patients, 15 patients had ptosis, 13 diplopia, 8 facial muscle weakness, 10 bulbar symptoms, 13 limb weakness, 14 neck weakness, 4 cardiac involvement, 6 respiratory involvement and 16 myalgia. Ocular, facial, cardiac and respiratory involvement and myalgia were more frequently observed than controls. Serum creatine kinase was increased to 5247 IU/L on average. Autoantibodies related to inflammatory myopathy were negative, while anti-striational antibodies were found in 13 (68%)patients. HLA-C*12:02 alleles were more frequently detected than healthy controls. Muscle pathology was characterized by multifocal necrotic myofibers with endomysial inflammation and expression of MHC class I. Immunosuppressive therapy with corticosteroids was generally effective for muscle weakness. Conclusions: Based on our clinical, histological and immunological findings, PD-1 myopathy is a discrete subset of inflammatory myopathy.

  • Three cases of non-carryover fingolimod-PML: Is the risk in Japan increased?

    Nakahara J., Tomaske L., Kume K., Takata T., Kamada M., Deguchi K., Kufukihara K., Schneider R., Gold R., Ayzenberg I.

    Neurology: Neuroimmunology and NeuroInflammation (Neurology: Neuroimmunology and NeuroInflammation)  6 ( 3 )  2019年05月

     概要を見る

    © 2019 American Academy of Neurology. ObjectiveTo report the course of 3 recent Japanese and European cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) and to analyze its risk factors and increased incidence in Japan.MethodsCase series and literature review.ResultsFingolimod-associated PML may cause both supratentorial and infratentorial lesions and a pronounced disability. Diagnosis can be challenging because PML lesions (especially infratentorial) can be initially misdiagnosed as extensive MS lesions. Immune reconstitution inflammatory syndrome (IRIS) develops a few weeks after fingolimod discontinuation and is usually mild. Age factor and therapy duration seem to be relevant because most reported patients were older than 45 years and were treated with fingolimod for more than 3 years. Combined IgG/IgM deficiency has been identified as a possible further predisposing condition in 1 case. Another patient developed an endogenous fungal skin infection, as a sign of generally compromised cellular immune response, shortly before PML. None of the reported patients had lymphocyte counts below 200/l. Two of the 3 reported and 4 of the 21 (19%) registered fingolimod-PML cases occurred in Japan (estimated risk of 0.652 per 1,000 compared with 0.083 per 1.000 worldwide).ConclusionsThe risk of PML under fingolimod is low, but there are no reliable predictors. Despite a mild IRIS phase, it causes profound disability. Patients older than 45 years, especially with known comorbid immunodeficiencies or manifestation of other opportunistic infections, should be monitored more closely. Increased surveillance and identification of further risk factors are urgently needed in Japan.

  • Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial

    Misawa S., Kuwabara S., Sato Y., Yamaguchi N., Nagashima K., Katayama K., Sekiguchi Y., Iwai Y., Amino H., Suichi T., Yokota T., Nishida Y., Kanouchi T., Kohara N., Kawamoto M., Ishii J., Kuwahara M., Suzuki H., Hirata K., Kokubun N., Masuda R., Kaneko J., Yabe I., Sasaki H., Kaida K., Takazaki H., Suzuki N., Suzuki S., Nodera H., Matsui N., Tsuji S., Koike H., Yamasaki R., Kusunoki S., Misawa S., Kuwabara S., Sato Y., Yamaguchi N., Nagashima K., Katayama K., Sekiguchi Y., Iwai Y., Amino H., Suichi T., Yokota T., Nishida Y., Kanouchi T., Kohara N., Kawamoto M., Ishii J., Kuwahara M., Suzuki H., Hirata K., Kokubun N., Masuda R., Kaneko J., Yabe I., Sasaki H., Kaida K., Takazaki H., Suzuki N., Suzuki S., Nodera H., Matsui N., Tsuji S., Koike H., Yamasaki R., Kusunoki S., Nagashima T., Shimizu T., Hirotani M., Kadoya M., Nakahara J., Shimizu J., Tanaka M., Sobue G., Katsuno M., Yamaguchi H., Ogata H.

    The Lancet Neurology (The Lancet Neurology)  17 ( 6 ) 519 - 529 2018年06月

    ISSN  14744422

     概要を見る

    © 2018 Elsevier Ltd Background: Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. Methods: This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3–5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Findings: Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42–78; n=14) in the eculizumab group, and 45% (20–73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. Interpretation: The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. Funding: The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.

  • Continuation of axitinib for advanced renal cell carcinoma by the application of homecare urology-a case report and literature review

    Yazawa S., Kato Y., Nakahara J., Miyata T., Oya M.

    Japanese Journal of Cancer and Chemotherapy (Japanese Journal of Cancer and Chemotherapy)  45 ( 4 ) 639 - 642 2018年04月

    ISSN  03850684

     概要を見る

    © 2018 Japanese Journal of Cancer and Chemotherapy Publishers Inc. All rights reserved. A 56-year-old man with advanced RCC and a past medical history of type 2 diabetes underwent a radical left nephrectomy following a histological diagnosis of papillary RCC, G2, INF β, pT3, V1 in 1999. In 2008, sorafenib was started to treat multiple pulmonary metastases of RCC. In 2011, sorafenib was switched to sunitinib when radiologic progression was observed. In 2014, sunitinib was switched to axitinib when further radiologic progression was observed. In 2015, the patient was referred to Yazawa clinic for homecare urology when hospital visits became difficult due to cancer pain and bilateral lower-extremity muscle weakness. Cancer pain was controlled using acetaminophen and a fentanyl patch. During the administration of axitinib, a CTCAE grade 1 vocal disorder was detected. We reduced the axitinib dose from 10 mg to 6 mg, and valsartan and an antiflatulent were administered due to CTCAE grade 2 hypertension and diarrhea, respectively. Axitinib administration continued until the patient died. He had survived more than 11 years following the detection of lung metastasis. In this patient, a good balance between cancer treatment and palliative care was achieved through the application of homecare urology. In a super-aged society such as Japan, urologists with an awareness of Zaitaku Medicine, a Japanese style of homecare that provides continuing appropriate medical treatment and welfare support to patients with access barriers to hospital treatment to enable them to live out the remainder of their lives with dignity, may play a key role in the development of Zaitaku Medicine.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • ミエリンマップ法を用いた多発性硬化症における髄鞘病理の画像解析

    2018年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 中原 仁, 基盤研究(C), 補助金,  代表

  • 髄鞘の可視化技術による多発性硬化症の病型分類に関する研究

    2013年04月
    -
    2016年03月

    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  代表

  • 髄鞘を標的とした神経変性疾患・脊髄損傷に対する新規治療戦略に関する研究

    2013年04月
    -
    2016年03月

    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  代表

  • アストロサイトによるin vivoケトン体生合成機構の解明

    2010年04月
    -
    2013年03月

    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), 中原仁, 補助金,  代表

  • 内在性オリゴデンドロサイト前駆細胞の分化誘導を基盤とする中枢神経系髄鞘再生医薬の開発

    2009年04月
    -
    2012年03月

    独立行政法人医薬基盤研究所, 保健医療分野における基礎研究推進事業, 中原仁, 受託研究,  代表

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知的財産権等 【 表示 / 非表示

  • Drug delivery system toward demyelinating lesion and biochemical marker of demyelinating lesions

    特願: 8252540  2012年08月 

    特許: 8252540  2012年08月

    特許, 共同

  • Medicinal compositions containing Fc receptor γ chain activator

    特願: 7901678  2011年03月 

    特許: 7901678  2011年03月

    特許, 共同

  • Fc受容体γ鎖活性化物質を含有する医薬組成物

    特願: 4214249  2008年11月 

    特許: 4214249  2008年11月

    特許, 共同

受賞 【 表示 / 非表示

  • Best Presentation賞

    2017年, Sendai Conference

  • MSJ-PACTRIMS investigator award

    2014年, Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)

  • 優秀指導教官賞

    2014年, 日本内科学会

  • MSJ-PACTRIMS Investigator賞

    2014年, 環アジア多発性硬化症治療研究会議

  • 優秀指導教官賞

    2014年, 内科学サミット2014

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担当授業科目 【 表示 / 非表示

  • 内科学(神経)講義

    2019年度

  • 内科学演習

    2019年度

  • 内科学実習

    2019年度

  • 組織学

    2019年度

  • 神経内科学臨床実習

    2019年度

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