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CHIHARA Norio
University Hospital / Neurology
Associate Professor

Researcher basic information

■ Research news
■ Research Keyword
  • Blood brain barrier
  • Dementia
  • Systems biology
  • Neuroimmunological diseases
  • Neuromyelitis Optica
  • Neuroimmunology
  • Multiple Sclerosis
  • Immune tolerance
  • co-inhibitory molecules
  • B cells
  • T cells
  • autoimmunity
■ Research Areas
  • Life sciences / Immunology
  • Life sciences / Neurology
■ Committee History
  • Oct. 2022 - Present, 日本臨床免疫学会, Midwinter Seminar小委員会 委員
  • Oct. 2022 - Present, The Japanese Society of Clinical Immunology, Representative
  • Aug. 2020 - Present, 厚生労働省 難治性疾患政策研究事業, 神経免疫疾患のエビデンスに基づく診断基準・重症度分類・ガイドラインの妥当性と患者QOLの検証研究班 研究協力者
  • Jul. 2020 - Present, 日本神経学会, 多発性硬化症・視神経脊髄炎ガイドライン作成委員会 委員
  • Sep. 2019 - Present, The Japanese Society for Neuroimmunology, Councilor

Research activity information

■ Award
  • Dec. 2020 神戸大学, 優秀若手研究者賞
    千原 典夫

  • Oct. 2019 内藤記念科学振興財団, 2019年度 科学奨励金・研究助成, 認知症を呈する自己免疫性辺縁系脳炎の病態解明(自己免疫介在性認知症の病態解明)
    千原 典夫

  • Aug. 2019 神戸大学医学部 第7回神緑会Young Investigator Award, 最優秀賞
    千原 典夫

  • Dec. 2018 上原記念生命科学財団, 2018年度 研究助成金, 神経免疫疾患におけるCysltr1 の免疫寛容機構の解明
    千原 典夫

  • Mar. 2014 日本学術振興会, 平成26年度 海外特別研究員, ヒト化TおよびB細胞受容体ダブルトランスジェニックマウスを用いたNMO病態の解明
    千原 典夫

  • Mar. 2013 上原記念生命科学財団, 平成24年度 海外留学助成ポストドクトラルフェローシップ, 高塩分食による自己免疫疾患発症とその制御
    千原 典夫

  • Mar. 2012 神戸大学, 平成23年度 神戸大学 優秀学生賞 (学術研究)
    千原 典夫

  • Sep. 2011 日本神経免疫学会, 第23回 日本神経免疫学会 学会賞
    千原 典夫

■ Paper
  • Kazuo Fujihara, Noriko Isobe, Katsuichi Miyamoto, Masaaki Niino, Jin Nakahara, Satoshi Hattori, Mamoru Yamamoto, Izumi Kawachi, Naoko Matsui, Chiyoko Nohara, Norito Kokubun, Norio Chihara, Tatsuro Misu, Kazumasa Okada, Katsuhisa Yamashita, Tadashi Nagatsuka, Hiroki Adachi, Ichiro Nakashima
    Mar. 2025, Multiple Sclerosis and Related Disorders, English
    Scientific journal

  • Shoji Yokobori, Tomoaki Yatabe, Yutaka Kondo, Yasuhiko Ajimi, Manabu Araki, Norio Chihara, Masao Nagayama, Tetsuya Samkamoto, the Japan Resuscitation Council (JRC) Neuroresuscitation Task Force and the Guidelines Editorial Committee, Hitoshi Kobata, Hajime Yoshimura, Michi Kawamoto, Masahiro Wakasugi, Hiroshi Yamagami, Hidetoshi Nakamoto, Eisei Hoshiyama, Kenichi Todo, Masaya Togawa, Mana Kurihara, Takashi Moriya, Ryuta Nakae, Hidetoshi Uchida, Sunghoon Yang, Masaaki Iwase
    Abstract Background Hepatic encephalopathy (HE) is a severe complication of acute hepatic failure requiring urgent critical care management. Branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine have been investigated as potential treatments to improve outcomes in patients with acute HE. However, the effectiveness of BCAA administration during the acute phase remains unclear. This study aimed to evaluate the effect of intravenous BCAA (IV-BCAA) treatment on clinical outcomes in patients with acute HE by systematically reviewing and analyzing randomized controlled trials (RCTs). Methods We conducted a comprehensive literature search of MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI), a Japanese database for medical literature. We included RCTs involving adult patients with acute HE who received IV-BCAA or placebo during the acute phase after admission (< 7 days). Two reviewers independently screened the citations and extracted data. The primary “critical” outcomes were mortality from any cause and improvement in disturbance of consciousness. The secondary “important” outcome included the incidence of complications such as nausea and diarrhea. Risk ratios (RRs) were calculated using random effects models with inverse variance weighting. Results Among the 2073 screened records, four met the criteria for quantitative analysis. The analysis included 219 patients: 109 received IV-BCAA, and 110 received placebo. Improvement in the disturbance of consciousness and mortality were not significantly different between the two groups (RR, 1.26; 95% confidence interval [CI], 0.96–1.66; RR, 0.90; 95% CI 0.70–1.16, respectively). Following IV-BCAA administration, the absolute differences of improvement in the disturbance of consciousness and mortality were 118 more per 1000 (95% CI 18 fewer–300 more) and 55 fewer per 1000 (95% CI 165 fewer–88 more), respectively. No significant differences were observed in the incidence of nausea or diarrhea between the two groups. Conclusions Our meta-analysis demonstrates that all outcomes were not significantly different between IV-BCAA treatment and placebo for acute HE. Further RCTs are required to better understand IV-BCAA treatment potential in patients with HE.
    Jan. 2025, Journal of Intensive Care, English
    Scientific journal

  • Takano, F., Ueda, K., Chihara, N., Arai, M., Sakamoto, M., Kurimoto, T., Yamada-Nakanishi, Y., Nakamura, M.
    Introduction: LHON complicated with extraocular symptoms is called LHON plus. We describe a case of Leber hereditary optic neuropathy (LHON) plus with a rare mutation, that also caused dystonia. Case Presentation: An 18-year-old male patient developed symptoms of dystonia at the age of 15 years. Two years later, he noticed decreased visual acuity and central scotoma in the left eye. One month later the same symptoms occurred in the right eye. Although the optic discs in both eyes revealed mildly redness and edematous change, no abnormal findings were detected on fluorescence fundus angiography and orbital magnetic resonance imaging. Mitochondrial deoxyribonucleic acid (mtDNA) sequencing detected the m.14487 T>C mutation. From clinical course and fundus findings, the case was diagnosed LHON. The optic nerve gradually atrophied and central scotoma remained. Conclusion: The m.14487 T>C mutation is one of the causative mutations in patients with dystonia or Leigh encephalopathy and a minor mutation in patients with LHON. However, in the present case, ocular symptoms were more severe than systematic symptoms and the disease course was consistent with LHON. For the above reasons, this case can be diagnosed as LHON plus. Whole mtDNA sequencing is important in diagnosing LHON if none of the three major mutations are detected.
    Nov. 2024, Case Reports in Ophthalmology, 15(1) (1), English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Mori, S., Chihara, N., Iwaki, Y., Okuda-Arai, M., Takano, F., Ueda, K., Sakamoto, M., Yamada-Nakanishi, Y., Matsumoto, R., Nakamura, M.
    Nov. 2024, Neuro-Ophthalmology, English
    Scientific journal

  • 多発性硬化症患者脳脊髄液のCD8+ T細胞上のPD-1発現上昇が良好な長期予後と相関する
    古東 秀介, 千原 典夫, 城間 京香, 辻 麻人, 刀坂 公崇, 西居 正汰, 的場 健人, 赤谷 律, 十河 正弥, 関口 兼司, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S236 - S236, Japanese

  • 労作時呼吸困難を呈した孤発性成人発症型ネマリンミオパチー疑いの一例
    福田 一帆, 古東 秀介, 千原 典夫, 宇田 有希, 岡田 誠央, 芦崎 太一朗, 十河 正弥, 的場 健人, 関口 兼司, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S437 - S437, Japanese

  • 神経生理検査から脊髄神経根障害と局在診断したサルコイドーシスの1例
    大村 晃太郎, 久後 啓介, 杉澤 良介, 橋本 黎, 的場 健人, 古東 秀介, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S437 - S437, Japanese

  • 急激の運動障害の増悪を呈したアレキサンダー病II型の一例
    沼 知里, 千原 典夫, 古東 秀介, 岡田 誠央, 宇田 有希, 矢幡 悟大, 武田 涼輔, 的場 俊, 的場 健人, 十河 正弥, 関口 兼司, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(Suppl.) (Suppl.), S438 - S438, Japanese

  • 呼吸停止に至ったが免疫治療により著明に改善した成人発症急性散在性脳脊髄炎(ADEM)の一例
    都留 朝希, 尾谷 真弓, 田中 智子, 杉澤 良介, 的場 健人, 古東 秀介, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(10) (10), 761 - 761, Japanese

  • 子宮頸癌に対する放射線化学療法後に発症した重症筋無力症関連筋炎の一例
    杉澤 良介, 古東 秀介, 都留 朝来, 田中 智子, 尾谷 真弓, 十河 正弥, 千原 典夫, 関口 兼司, 西野 一三, 松本 理器
    (一社)日本神経学会, Oct. 2024, 臨床神経学, 64(10) (10), 761 - 761, Japanese

  • 強制正常化をきたし治療に難渋した右前頭葉てんかんの1例
    芦崎 太一朗, 十河 正弥, 的場 健人, 南 霧子, 久後 啓介, 杉澤 良介, 城間 京香, 尾谷 真弓, 古東 秀介, 千原 典夫, 関口 兼司, 蓬莱 政, 菱本 明豊, 松本 理器
    (一社)日本てんかん学会, Sep. 2024, てんかん研究, 42(2) (2), 483 - 483, Japanese

  • Kenji Sekiguchi, Seiji Kawano, Norio Chihara, Seimi Satomi-Kobayashi, Eiichi Maeda, Riki Matsumoto
    Aug. 2024, JMIR Formative Research
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 認知機能低下を契機に診断に至りcARTが奏効したAIDSの一例
    板垣 実幸, 的場 健人, 坂東 美樹, 渡邊 有史, 辻 麻人, 十河 正弥, 古東 秀介, 千原 典夫, 関口 兼司, 松本 理器
    (一社)日本神経学会, Aug. 2024, 臨床神経学, 64(8) (8), 604 - 604, Japanese

  • Niino, M., Isobe, N., Araki, M., Ohashi, T., Okamoto, T., Ogino, M., Okuno, T., Ochi, H., Kawachi, I., Shimizu, Y., Takahashi, K., Takeuchi, H., Tahara, M., Chihara, N., Nakashima, I., Fukaura, H., Misu, T., Miyazaki, Y., Miyamoto, K., Mori, M., Kinoshita, M., Takai, Y., Fujii, C., Watanabe, M., Fujihara, K.
    Aug. 2024, Multiple Sclerosis and Related Disorders, 90, English
    [Refereed]
    Scientific journal

  • Ritsu Akatani, Norio Chihara, Atsushi Hara, Asato Tsuji, Shusuke Koto, Kazuhiro Kobayashi, Tatsushi Toda, Riki Matsumoto
    BACKGROUND AND OBJECTIVES: Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. METHODS: Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19+ IgD-, CD27-) and plasmablasts (PBs; CD19+, CD27hi, CD38hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab. RESULTS: DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200+ PBs produced more IL-10 than CD200- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200+ PBs than patients during the acute attacks. DISCUSSION: Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200+ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.
    Corresponding, Jul. 2024, Neurology(R) neuroimmunology & neuroinflammation, 11(4) (4), e200266, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Koto, S., Chihara, N., Hara, A., Matsumoto, R.
    Corresponding, Feb. 2024, Clinical and Experimental Neuroimmunology, 15(1) (1)
    [Refereed][Invited]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ritsu Akatani, norio chihara, Shusuke Koto, Sotaro Mori, Takuji Kurimoto, Makoto Nakamura, Hisatsugu Tachibana, Yoshihisa Otsuka, Takehiro Ueda, Takashi Omori, Kenji Sekiguchi, Riki Matsumoto
    Corresponding, Jan. 2024, Immunological Medicine, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Taichiro Ashizaki, Masaya Togo, Miki Bando, Rei Hashimoto, Kento Matoba, Shusuke Koto, Norio Chihara, Kenji Sekiguchi, Riki Matsumoto
    Japan Stroke Society, 2024, Japanese Journal of Stroke
    [Refereed]
    Scientific journal

  • Takako Matsuoka, Manabu Araki, Youwei Lin, Tomoko Okamoto, Ralf Gold, Norio Chihara, Wakiro Sato, Atsuko Kimura, Hisateru Tachimori, Katsuichi Miyamoto, Susumu Kusunoki, Takashi Yamamura
    BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune neurologic disease. Anti-IL-6 receptor (IL-6R) therapy prevents relapses in patients with anti-aquaporin 4 (AQP4)-IgG-positive NMOSD; however, it remains unclear how cellular immune components are altered by anti-IL-6R therapy. In this study, we examined the long-term effects of the anti-IL-6R monoclonal antibody tocilizumab (TCZ) on immune cell profiles in patients with NMOSD. METHODS: Monthly IV injections of TCZ (8 mg/kg) were administered as an add-on therapy to 19 anti-AQP4-IgG-positive patients, who had been refractory to corticosteroids and immunosuppressive drugs. Peripheral blood was collected before infusion of TCZ for flow cytometry analysis of lymphocyte subsets. Seven patients provided whole blood samples for gene expression profiles. RESULTS: Patients with NMOSD had reduced numbers of lymphocyte subsets with regulatory functions, including transitional B cells, CD56high NK cells, and CD45RA-FoxP3high regulatory T cells. However, after initiating TCZ therapy, the numbers increased to normal levels within 1 year. Gene expression analysis revealed that neutrophil granule-related genes, predominated by those related to azurophil granules, were significantly upregulated in patients with NMOSD. Such alterations suggestive of accelerated myeloid turnover were not observed 1 year after TCZ therapy, and the effects of TCZ on some neutrophil genes were observed as early as 5 days after starting TCZ. In vitro analysis demonstrated that naïve T-cell division was impaired in the enrolled patients, which was fully recovered after 18 months of therapy. DISCUSSION: In patients with active NMOSD not treated with molecular targeting drugs, we observed reduction or deficiency in lymphocytes with regulatory potentials and activation of neutrophils. However, introduction of anti-IL-6R therapy accompanied by tapering concomitant drugs corrected such abnormalities, which might contribute to persistent relapse prevention. The recovery in the naïve T-cell division after starting TCZ may underlie the relatively low risk of infection in patients under anti-IL-6R therapy. TRIAL REGISTRATION INFORMATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000005889 (July 8, 2011) and UMIN000007866 (May 1, 2012) (umin.ac.jp/ctr/index.htm). The first participant was enrolled on November 2, 2011.
    Jan. 2024, Neurology(R) neuroimmunology & neuroinflammation, 11(1) (1), English, International magazine
    [Refereed]
    Scientific journal

  • 【神経変性疾患に伴う神経炎症】多発性硬化症における神経炎症
    千原 典夫
    (有)科学評論社, Dec. 2023, 脳神経内科, 99(6) (6), 819 - 824, Japanese
    [Invited]

  • 坂本 光弘, 千原 典夫, 松本 理器
    (株)メディカルレビュー社, Dec. 2023, Epilepsy: てんかんの総合学術誌, 17(2) (2), 115 - 123, Japanese
    [Invited]

  • Relationship between cortical tuber MRI subtypes and interictal discharges in tuberous sclerosis complex: a scalp EEG study
    K Masamune, M Togo, K Koda, K Morimoto, K Matoba, S Koto, N Chihara, K Sekiguchi, Y Fujimoto, K Chiba, H Nagase, R Matsumoto
    Nov. 2023, EPILEPSIA, 64, 241
    [Refereed]

  • 千原 典夫
    日本神経眼科学会, Nov. 2023, 神経眼科, 40(増補1) (増補1), 47 - 47, Japanese
    [Invited]

  • Alexandra Schnell, Linglin Huang, Brianna M L Regan, Vasundhara Singh, Dominik Vonficht, Alina Bollhagen, Mona Wang, Yu Hou, Lloyd Bod, Raymond A Sobel, Norio Chihara, Asaf Madi, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
    Co-inhibitory and checkpoint molecules suppress T cell function in the tumor microenvironment, thereby rendering T cells dysfunctional. Although immune checkpoint blockade is a successful treatment option for multiple human cancers, severe autoimmune-like adverse effects can limit its application. Here, we show that the gene encoding peptidoglycan recognition protein 1 (PGLYRP1) is highly coexpressed with genes encoding co-inhibitory molecules, indicating that it might be a promising target for cancer immunotherapy. Genetic deletion of Pglyrp1 in mice led to decreased tumor growth and an increased activation/effector phenotype in CD8+ T cells, suggesting an inhibitory function of PGLYRP1 in CD8+ T cells. Surprisingly, genetic deletion of Pglyrp1 protected against the development of experimental autoimmune encephalomyelitis, a model of autoimmune disease in the central nervous system. PGLYRP1-deficient myeloid cells had a defect in antigen presentation and T cell activation, indicating that PGLYRP1 might function as a proinflammatory molecule in myeloid cells during autoimmunity. These results highlight PGLYRP1 as a promising target for immunotherapy that, when targeted, elicits a potent antitumor immune response while protecting against some forms of tissue inflammation and autoimmunity.
    Nov. 2023, Nature immunology, 24(11) (11), 1908 - 1920, English, International magazine
    [Refereed]
    Scientific journal

  • PD-1 positive CD8+ T cells are associated with better clinical outcomes in patients with the early stage of multiple sclerosis
    Norio Chihara, Shusuke Koto, Ritsu Akatani, Asato Tsuji, Kimitaka Katanazaka, Shota Nishii, Ryosuke Takeda, Kyoka Shiroma, Kenji Sekiguchi, Riki Matsumoto
    Oct. 2023, MULTIPLE SCLEROSIS JOURNAL, 29, 814 - 815
    [Refereed]

  • 千原 典夫
    (一社)日本神経治療学会, Jul. 2023, 神経治療学, 40(4) (4), 606 - 609, Japanese
    [Invited]

  • Tomoko Tanaka, Masaya Togo, Kiminobu Okayama, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Riki Matsumoto
    We report two male patients who had a sensory seizure, which evolved into a focal impaired awareness tonic seizure, and after that, focal to bilateral tonic-clonic seizure. The first case, a 20-year-old man had been treated with steroids for anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis. His seizure started with abnormal sensation in the little finger of the left hand, which spread to the left upper and then to the left lower limb. The seizure then evolved into tonic seizures of the upper and lower limbs and he finally lost awareness. The second case, a 19-year-old man experienced floating dizziness while walking, followed by numbness and a pain-like electrical shock in the right upper limb. The right arm somatosensory seizure evolved into a right upper and lower limb tonic seizure, which spread to the bilateral limbs, and finally he lost awareness. Symptoms of both patients improved after the treatment with steroids. Both patients shared a similar high-intensity FLAIR lesion in the posterior midcingulate cortex. Both patients were diagnosed with MOG antibody-positive cerebral cortical encephalitis because of a positive titer of anti-MOG antibody in the serum. Several reports showed involvement of the cingulate gyrus in MOG antibody-positive cerebral cortical encephalitis, but only a few reported seizure semiology in detail. The semiology reported here is consistent with that of cingulate epilepsy or the findings of electrical stimulation of the cingulate cortex, namely, somatosensory (electric shock or heat sensation), motor (tonic posture), and vestibular symptoms (dizziness). Cingulate seizures should be suspected when patients show somatosensory seizures or focal tonic seizures. MOG antibody-positive cerebral cortical encephalitis should be considered as one of the differential diagnoses when the young patient shows the unique symptoms of an acute symptomatic cingulate seizure.
    Jun. 2023, Rinsho shinkeigaku = Clinical neurology, Japanese, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kenji Sekiguchi, Seiji Kawano, Norio Chihara, Seimi Satomi-Kobayashi, Eiichi Maeda, Riki Matsumoto
    Jun. 2023

  • 千原 典夫
    (一社)日本神経治療学会, May 2023, 神経治療学, 40(3) (3), 311 - 314, Japanese
    [Invited]

  • Norio Chihara, Asato Tsuji, Riki Matsumoto
    May 2023, Clinical and Experimental Neuroimmunology
    [Refereed][Invited]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Vera Bril, Artur Drużdż, Julian Grosskreutz, Ali A. Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, John Vissing, Tuan Vu, Marion Boehnlein, Bernhard Greve, Franz Woltering, Ali Bozorg, Maryam Gayfieva, Henry J. Kaminski, Angela Genge, Rami Massie, Maxime Berube, Vera Bril, Lubna Daniyal, Shabber Mannan, Eduardo Ng, Ritesh Rohan Raghu Raman, Evelyn Sarpong, Monica Alcantara, Annie Dionne, Zaeem Siddiqi, Derrick Blackmore, Faraz Hussain, Genevieve Matte, Stephan Botez, Michaela Tyblova, Michala Jakubikova, Jana Junkerova, John Vissing, Nanna Witting, Sonja Holm-Yildiz, Mads Stemmerik, Henning Andersen, Izabella Obál, Guilhem Solé, Stéphane Mathis, Marie Hélène Violleau, Christine Tranchant, Sihame Messai, Jean Baptiste Chanson, Aleksandra Nadaj-Pakleza, Arnaud Verloes, Leila Zaidi, Sabrina Sacconi, Manuela Gambella, Michele Cavalli, Tanya Stojkovic, Sophie Demeret, Loic Le Guennec, Giorgia Querin, Nicolas Weiss, Marion Masingue, Laurent Magy, Karima Ghorab, Ia Rukhadze, Alexander Tsiskaridze, Marina Janelidze, Temur Margania, Florian Then Bergh, Eike Hänsel, Andrea Kalb, Bianca Meilick, Mandy Reuschel, Lars Malte Teußer, Astrid Unterlauft, Clemens Goedel, Tim Hagenacker, Andreas Totzeck, Benjamin Stolte, Franz Blaes, Christine Bindler, Vasilios Tsoutsikas, Annekathrin Roediger, Christian Geis, Jens Schmidt, Jana Zschüntzsch, Margret Schwarz, Stefanie Meyer, Karsten Kummer, Stefanie Glaubitz, Rachel Zeng, Heinz Wiendl, Luisa Klotz, Anna Lammerskitten, Jan Lünemann, Péter Diószeghy, Renato Mantegazza, Lorenzo Maggi, Elena Rinaldi, Matteo Gastaldi, Federico Mazzacane, Pietro Businaro, Raffaele Iorio, Giovanni Antonini
    Background: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might provide a novel therapeutic option for myasthenia gravis. We aimed to assess the safety and efficacy of rozanolixizumab for generalised myasthenia gravis. Methods: MycarinG is a randomised, double-blind, placebo-controlled, adaptive phase 3 study done at 81 outpatient centres and hospitals in Asia, Europe, and North America. We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America class II–IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (non-ocular symptoms), and a quantitative myasthenia gravis score of at least 11. Patients were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg, or placebo. Randomisation was stratified by AChR and MuSK autoantibody status. Investigators, patients, and people assessing outcomes were masked to random assignments. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020-003230-20). Findings: Between June 3, 2019, and June 30, 2021, 300 patients were assessed for eligibility, of whom 200 were enrolled. 66 (33%) were randomly assigned to rozanolixizumab 7 mg/kg, 67 (34%) to rozanolixizumab 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change –3·37 [SE 0·49]) and in the rozanolixizumab 10 mg/kg group (–3·40 [0·49]) than with placebo (–0·78 [0·49]; for 7 mg/kg, least-squares mean difference −2·59 [95% CI −4·09 to −1·25], p<0·0001; for 10 mg/kg, −2·62 [−3·99 to −1·16], p<0·0001). TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 10 mg/kg group, and 13 [19%] in the placebo group), diarrhoea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. Interpretation: Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. Funding: UCB Pharma.
    May 2023, The Lancet Neurology, 22(5) (5), 383 - 394
    [Refereed]
    Scientific journal

  • Atsushi Hara, Norio Chihara, Ritsu Akatani, Ryusei Nishigori, Asato Tsuji, Hajime Yoshimura, Michi Kawamoto, Yoshihisa Otsuka, Yasufumi Kageyama, Takayuki Kondo, Frank Leypold, Klaus-Peter Wandinger, Riki Matsumoto
    Autoimmune epilepsy (AE) is an inflammatory disease of the central nervous system with symptoms that have seizures that are refractory to antiepileptic drugs. Since the diagnosis of AE tends to rely on a limited number of anti-neuronal antibody tests, a more comprehensive analysis of the immune background could achieve better diagnostic accuracy. This study aimed to compare the characteristics of anti-neuronal antibody-positive autoimmune epilepsy (AE/Ab(+)) and antibody-negative suspected autoimmune epilepsy (AE/Ab(-)) groups. A total of 23 patients who met the diagnostic criteria for autoimmune encephalitis with seizures and 11 healthy controls (HC) were enrolled. All patients were comprehensively analyzed for anti-neuronal antibodies; 13 patients were identified in the AE/Ab(+) group and 10 in the AE/Ab(-) group. Differences in clinical characteristics, including laboratory and imaging findings, were evaluated between the groups. In addition, the immunophenotype of peripheral blood mononuclear cells (PBMCs) and CSF mononuclear cells, particularly B cells and circulating Tfh (cTfh) subsets, and multiplex assays of serum and CSF were analyzed using flow cytometry. Patients with AE/Ab(+) did not show any differences in clinical parameters compared to patients with AE/Ab(-). However, the frequency of plasmablasts within PBMCs and CSF in patients with AE/Ab(+) was higher than that in patients with AE/Ab(-) and HC, and the frequency of cTfh17 cells and inducible T-cell co-stimulator (ICOS) expressing cTfh17 cells within cTfh subsets was higher than that in patients with AE/Ab(-). Furthermore, the frequency of ICOShighcTfh17 cells was positively correlated with that of the unswitched memory B cells. We also found that IL-12, IL-23, IL-6, IL-17A, and IFN-γ levels were elevated in the serum and IL-17A and IL-6 levels were elevated in the CSF of patients with AE/Ab(+). Our findings indicate that patients with AE/Ab(+) showed increased differentiation of B cells and cTfh subsets associated with antibody production. The elevated frequency of plasmablasts and ICOS expressing cTfh17 shift in PBMCs may be indicative of the presence of antibodies in patients with AE.
    Corresponding, Frontiers Media {SA}, Dec. 2022, Frontiers in Immunology, 13, 1048428 - 1048428, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kento Matoba, MD, Norio Chihara, Wataru Satake, Hideki Tokuoka, Yoshihisa Otsuka, Takehiro Ueda, Kenji Sekiguchi, Masayuki Itoh, Riki Matsumoto
    BACKGROUND AND OBJECTIVES: We describe 2 long-surviving siblings with a mild phenotype of Joubert syndrome (JBTS) harboring a novel compound heterozygous missense variant in the CPLANE1 gene. METHODS: Targeted sequencing data of 2 middle-aged siblings (sister and brother) with JBTS were analyzed. RESULTS: The patients were older than 60 years and presented with an inborn facial anomaly and ataxia, accompanied by a molar tooth sign on brain MRI. The male patient showed mild intellectual disability, abnormal eye movements, and progressive gait disturbance. Targeted sequencing revealed a compound heterozygous missense variant of CPLANE1 p.Arg1193Cys_Gln1223Pro; c.3577C>T_3668A>C. Multiple in silico assays predicted that the missense sites were pathogenic. DISCUSSION: The phenotype-genotype correlation of CPLANE1 remains controversial, although many cases have been previously reported in children and young adults. Our study revealed a novel pathogenic variant of CPLANE1 in patients, confirming the role of this gene in JBTS, thus providing an opportunity for neurologists to recognize JBTS as a differential diagnosis for chronic progressive ataxia in an aging society.
    Corresponding, Oct. 2022, Neurology Genetics, 8(5) (5), e200031, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Sekiguchi K, Kawano S, Chihara N, Kobayashi S, Maeda E, Matsumoto R
    Aug. 2022
    [Refereed]
    Scientific journal

  • Shusuke Koto, Norio Chihara, Ritsu Akatani, Hiroko Nakano, Atsushi Hara, Kenji Sekiguchi, Riki Matsumoto, Tatsushi Toda
    BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. CD8+ T cells are prominently found at inflammatory sites. Recent advances in understanding checkpoint molecules, including programmed cell death 1 (PD-1), expressed on CD8+ T cells, highlight the immune regulatory roles of this T-cell subset; however, the role of CD8+ T cells in MS is unclear. Thus, we aimed to reveal the characteristics of PD-1-expressed (PD-1+) CD8+ T cells in MS. METHODS: We performed a cohort, case-control study for phenotyping analysis of PD-1+CD8+ T cells in disease remission and flare states using CSF and peripheral blood samples of 45 patients with MS or clinically isolated syndrome and 12 healthy subjects. We further analyzed the transcriptome of sorted PD-1+CD8+ T cells obtained from interferon (IFN)-β-treated patients and validated their regulatory machinery using in vitro cell culture assays with lentiviral gene transfer. RESULTS: In the disease remission state, PD-1+CD8+ T cells were decreased in the peripheral blood of patients with MS and resolved in patients treated with IFN-β treatment who showed immune regulatory cytokine interleukin (IL)-10 expression. In the disease flare state, we found that PD-1+CD8+ T cells were enriched in the CSF, which predicted a good response to subsequent IV steroid therapy. Transcriptome analysis of sorted PD-1+CD8+ T cells revealed the transcription factor c-Maf as a potential major regulator of the gene module, including multiple coinhibitory molecules. Furthermore, c-Maf expressed in CD8+ T cells induced PD-1 expression and production of IL-10 as well as suppressed alloactivated CD4+ T-cell survival. DISCUSSION: This study uncovered a favorable role of PD-1+CD8+ T cells against MS and demonstrated that c-Maf-driven IL-10 is an immune regulatory machinery.
    Corresponding, Jul. 2022, Neurology(R) neuroimmunology & neuroinflammation, 9(4) (4), English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Norio Chihara, Takashi Yamamura
    Neuromyelitis optica (NMO) is an inflammatory disease that resembles MS in the relapsing clinical course of optic neuritis and myelitis. Two decades of studies have revealed that autoantibodies, reactive to the water channel protein aquaporin 4 (AQP4) are detected in the core group of patients. These autoantibodies play a crucial role in the inflammatory pathology of NMO, involving proinflammatory cytokines, chemokines, and various inflammatory cells such as Th17 cells. Anti-AQP4 antibody-positive NMO differs fundamentally from MS, particularly in the responsiveness to therapies and the neuropathology accompanying destruction of astrocytes. Research into the immunological mechanism has led to the identification of possible targets of therapy, including complement pathway and interleukin-6 (IL-6) receptor signaling. Recent randomized controlled clinical trials have shown the remarkable efficacy of antibodies specific for complement C5, IL-6 receptor, and CD19+ B cells in prevention of NMO spectrum disorder relapses, although no such effects were found in anti-AQP4 antibody-negative patients. These results imply that anti-AQP4 antibody is a biomarker predicting the efficacy of therapies, and indicate the future direction towards "precision medicine."
    Lead, May 2022, Seminars in immunopathology, English, International magazine
    [Refereed]
    Scientific journal

  • Hiroaki Sekiya, Shunsuke Koga, Yoshihisa Otsuka, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Yukihiro Yoneda, Yasufumi Kageyama, Riki Matsumoto, Dennis Dickson
    Ovid Technologies (Wolters Kluwer Health), May 2022, Neurology, 98(18_supplement) (18_supplement)
    [Refereed]
    Scientific journal

  • 千原 典夫
    (株)日本臨床社, May 2022, 日本臨床, 80(増刊5 免疫性神経疾患) (増刊5 免疫性神経疾患), 564 - 568, Japanese
    [Invited]

  • Kazuma Koda, Ai Makino, Masaaki Yoshikawa, Hitomi Nishioka, Kiminobu Okayama, Masaya Togo, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Riki Matsumoto
    WILEY, Apr. 2022, NEUROLOGY AND CLINICAL NEUROSCIENCE, English
    [Refereed]
    Scientific journal

  • Hiroaki Sekiya, Shunsuke Koga, Yoshihisa Otsuka, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Yukihiro Yoneda, Yasufumi Kageyama, Riki Matsumoto, Dennis W Dickson
    BACKGROUND: In the current consensus criteria, onset after age 75 is considered as non-supporting for diagnosis of multiples system atrophy (MSA); however, some MSA patients present after age 75. Clinical and pathological characteristics of such later onset MSA (LO-MSA) compared to usual onset MSA (UO-MSA) remain poorly understood. METHODS: The clinical cohort included patients from Kobe University Hospital and Amagasaki General Medical Center Hospital, while the autopsy cohort was from the brain bank at Mayo Clinic Florida. We identified 83 patients in the clinical cohort and 193 patients in the autopsy cohort. We divided MSA into two groups according to age at onset: UO-MSA (≤ 75) and LO-MSA (> 75). We compared clinical features and outcomes between the two groups in the clinical cohort and compared the findings to the autopsy cohort. RESULTS: LO-MSA accounted for 8% in the clinical cohort and 5% in the autopsy cohort. The median time from onset to death or to life-saving tracheostomy was significantly shorter in LO-MSA than in UO-MSA in both cohorts (4.8 vs 7.9 years in the clinical cohort and 3.9 vs 7.5 years in the autopsy cohort; P = 0.043 and P < 0.0001, respectively). The median time from diagnosis to death was less than 3 years in LO-MSA in the clinical cohort. CONCLUSIONS: Some MSA patients have late age of onset and short survival, limiting time for clinical decision making. MSA should be considered in the differential diagnosis of elderly patients with autonomic symptoms and extrapyramidal and/or cerebellar syndromes.
    Mar. 2022, Journal of neurology, 269(8) (8), 4310 - 4321, English, International magazine
    [Refereed]
    Scientific journal

  • 一角 朋子, 仙石 淳, 原 敦, 千原 典夫, 松本 理器, 奥田 志保
    症例は76歳女性。2019年10月頃より両手の不随意運動と歩行障害を認めた。口渇を自覚し、飲水量が多くなっていた。次第に両下肢の筋力低下が悪化し、2020年1月上旬の受診時に痙性対麻痺と感覚性運動失調、トレンデンブルグ歩行を認めた。脊髄MRIで頸髄から胸髄にかけて長大な髄内病変を認め、血液検査で抗ヒトT細胞白血病ウイルス(HTLV-1)抗体が陽性であった。2月下旬に他院に入院した際は歩行器歩行となっていた。亜急性の経過から急速進行性HTLV-1関連脊髄症(HAM)と診断した。ステロイドパルス療法を2クール施行後プレドニゾロン内服を開始した。3月下旬に、他院の回復期リハビリテーション病棟に転院した。ステロイド内服治療を継続し、リハビリテーション治療を行った結果、歩行障害や日常生活活動(ADL)、手段的ADLが改善した。
    (公社)日本リハビリテーション医学会, Feb. 2022, The Japanese Journal of Rehabilitation Medicine, 59(2) (2), 217 - 222, Japanese
    [Refereed]

  • 自己免疫性脳炎の疾患活動期では末梢血でplasmablastsが増加する
    原 敦, 千原 典夫, 赤谷 律, 辻 麻人, 刀坂 公崇, 錦織 隆成, 近藤 誉之, 塩見 悠真, 橋本 黎, 吉村 元, 川本 未知, 松本 理器
    (一社)日本神経免疫学会, Oct. 2021, 神経免疫学, 26(1) (1), 134 - 134, Japanese

  • 千原 典夫
    視神経脊髄炎(NMO)は、中枢神経系の再発性炎症性疾患で、1回の再発が重篤な神経後遺症を招く。NMO患者の多くではアストロサイトに発現するアクアポリン4(AQP4)に反応する自己抗体(抗AQP4抗体)が認められ、自己反応性T細胞およびB細胞の活性化、抗AQP4抗体の産生、および抗AQP4抗体を介した補体依存性のアストロサイト障害が一連の病態として解明されてきた。最近の臨床試験では、抗AQP4抗体陽性NMO患者における補体C5、IL-6受容体、およびB細胞表面分子を標的とする抗体医薬の有効性が示されている。本稿では、本疾患で解明されてきた病態機構とそれを標的として実装された分子標的治療薬について概説する。(著者抄録)
    (株)羊土社, Sep. 2021, 実験医学, 39(15) (15), 2455 - 2461, Japanese
    [Invited]

  • Takahiro Nakano, Norio Chihara, Kento Matoba, Hisatsugu Tachibana, Shiho Okuda, Yoshihisa Otsuka, Takehiro Ueda, Kenji Sekiguchi, Hisatomo Kowa, Frank Leypoldt, Klaus-Peter Wandinger, Riki Matsumoto
    A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis. Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.
    Corresponding, Jul. 2021, Internal medicine (Tokyo, Japan), 61(3) (3), 419 - 423, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Suguru Mitsui, Yugo Tanaka, Kenji Kimura, Naoe Jimbo, Norio Chihara, Yoshimasa Maniwa
    Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.
    Apr. 2021, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia, English, Domestic magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kimitaka Katanazaka, Norio Chihara, Sayaka Akazawa, Takehiro Ueda, Kenji Sekiguchi, Riki Matsumoto
    We report a 60-year-old woman who developed spinal cord infarction (SCI) with anti-aquaporin (AQP) 4 antibody seropositive. She was admitted to our hospital with acute onset of flaccid paraparesis and urinary disturbances that completed within a few minutes after acute pain in her lower back. Neurological examination revealed flaccid paraparesis, bladder and bowel dysfunction and dissociated sensory loss below the level of Th11 spinal cord segment. Diffusion weighted imaging (DWI) and T2-wighted imaging (T2WI) of thoracic spine MRI showed high signal intensity in the spinal cord between Th9 and Th12 vertebral levels with decreased apparent diffusion coefficient (ADC). We diagnosed her as having SCI. Thereafter the serum examination on admission was reported as positive for anti-aquaporin 4 (AQP4) antibody. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, and the spinal cord lesions became enlarged in MRI on 12 days after the onset. We, therefore, suspected that the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) accompanied SCI. The patient underwent two courses of high dose intravenous methylprednisolone (IVMP) for three days (1 g/day). Her neurological symptoms did not improve significantly, but the size of T2WI MRI high signal lesion improved to that of the initial MRI scan. Anti-AQP4 antibody seropositivity may have modified the SCI pathology in the present patient.
    Corresponding, Feb. 2021, Rinsho shinkeigaku = Clinical neurology, 61(2) (2), 127 - 131, Japanese, Domestic magazine
    [Refereed]
    Scientific journal

  • Norio Chihara, Riki Matsumoto, Takashi Yamamura
    Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory disease of the central nervous system in which even a single disease flare may result in persistent neurological disability. The core group of patients with NMOSD, characterized by prominent astrocyte pathology, has high levels of autoantibodies reactive to aquaporin-4 (AQP4), a water channel expressed on astrocytes. In these patients, activation of autoreactive T and B cells, production of AQP4 autoantibody (AQP4-Ab) and AQP4-Ab-mediated complement-dependent destruction of astrocytes are presumed be the critical events in the pathology. Recent clinical trials have shown the efficacy of therapeutic antibodies targeting complement C5, interleukin-6 receptor (IL-6R) and CD19+ B cells in patients with NMOSD, particularly those with AQP4-Ab seropositivity. Regarding the pathogenesis of NMOSD, prior studies have indicated that IL-6 promotes the activation of autoreactive T cells, prolongs the survival of AQP4-Ab-producing B cells and inhibits blood–brain barrier integrity. The results of two pivotal clinical trials showing the efficacy of satralizumab have firmly established the role of IL-6 and IL-6R signalling in the pathogenesis of AQP4-Ab-positive NMOSD. This review aims to evaluate the involvement of IL-6 in NMOSD and the potential of satralizumab, a humanized antibody against IL-6R, in the current and future practice of NMOSD.
    2021, touchREVIEWS in Neurology, 17(1) (1), 11 - 15
    [Refereed][Invited]

  • 千原 典夫
    (公財)上原記念生命科学財団, Dec. 2020, 上原記念生命科学財団研究報告集, 34, 1 - 5, Japanese
    [Invited]

  • 【神経疾患と慢性炎症】多発性硬化症における免疫・神経連関
    千原 典夫
    過剰な免疫応答は自己免疫疾患の原因となる。神経系も例外ではなく、これまで神経炎症や神経変性過程における全身性の免疫応答の特徴を解析し、神経組織細胞と免疫細胞の相互作用を解明する研究が多発性硬化症などの免疫性神経疾患の治療に繋がってきた。神経組織は血液脳関門により保護されている一方で、神経細胞には十分な自己再生能がなく、その障害機序の解明と治療法の開発には、神経細胞障害の予防という観点からさまざまな因子を考慮しなければならない。本稿では多発性硬化症について、炎症の介在する神経障害の機序や治療戦略について最新の知見を含め紹介する。(著者抄録)
    (株)北隆館, Dec. 2020, 別冊Bio Clinica: 慢性炎症と疾患, 9(2) (2), 16 - 21, Japanese
    [Invited]

  • T細胞における共抑制性受容体遺伝子群とその制御機構の解明
    千原 典夫
    (一社)神緑会, Dec. 2020, 神緑会学術誌, 36, 52 - 56, Japanese
    [Invited]

  • 神経免疫疾患におけるCysltr1の免疫寛容機構の解明
    千原 典夫
    (公財)上原記念生命科学財団, Dec. 2020, 上原記念生命科学財団研究報告集, 34, 1 - 5, Japanese
    [Invited]

  • Huiyuan Zhang, Asaf Madi, Nir Yosef, Norio Chihara, Amit Awasthi, Caroline Pot, Conner Lambden, Amitabh Srivastava, Patrick R Burkett, Jackson Nyman, Elena Christian, Yasaman Etminan, Annika Lee, Helene Stroh, Junrong Xia, Katarzyna Karwacz, Pratiksha I Thakore, Nandini Acharya, Alexandra Schnell, Chao Wang, Lionel Apetoh, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
    Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, and Atf3) and 2 negative (Irf9 and Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators, Prdm1 and Maf, that cooperatively drive the expression of signature genes induced by IL-27 in type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3+ regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying ll10-deficient mice. Our work provides insights into IL-27-driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.
    Nov. 2020, Cell reports, 33(8) (8), 108433 - 108433, English, International magazine
    [Refereed]
    Scientific journal

  • Norio Chihara
    Nov. 2020, Journal of neurology, neurosurgery, and psychiatry, English, International magazine
    [Invited]

  • Sotaro Mori, Takuji Kurimoto, Yusuke Murai, Kaori Ueda, Mari Sakamoto, Norio Chihara, Yuko Yamada-Nakanishi, Makoto Nakamura
    Purpose. Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. Design. Retrospective observational study, clinical case series. Methods. We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. Results. Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy ( p = 0.02 ). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy ( p < 0.01 ). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. Conclusions. Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities.
    Hindawi Limited, Nov. 2020, Journal of Ophthalmology, 2020, 1 - 6, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Sotaro Mori, Takuji Kurimoto, Kaori Ueda, Mari Sakamoto, Norio Chihara, Wataru Satake, Yuko Yamada-Nakanishi, Makoto Nakamura
    Purpose: We report a case of neurosarcoidosis that presented simultaneously with oculomotor nerve palsy, contralateral abducens nerve palsy, and paresthesia of both lower limbs. Observations: A 69-year-old Japanese woman who suffered from repeated diplopia and lower-limb paresthesia was referred to our hospital. Ophthalmic findings included oculomotor nerve and contralateral abducens nerve palsies. No remarkable abnormalities were detected via enhanced brain magnetic resonance imaging (MRI), chest X-ray, and cerebrospinal fluid analysis. Chest computed tomography (CT) was performed to exclude neoplastic lesions; this revealed right hilar lymphadenopathy, and positron emission tomography MRI showed strong 18-F fluorodeoxyglucose uptake in the hilar lymph node. Biopsy of the lymph node showed non-caseating epithelioid granulomatous tissue, leading to a diagnosis of probable neurosarcoidosis. After the initiation of oral prednisolone treatment, the patient experienced complete remission without any recurrence. Conclusions and importance: When examining a patient presenting with multiple cranial neuropathies of unknown cause, neurosarcoidosis should be considered as a differential diagnosis and chest CT should be performed even when the chest X-ray and angiotensin-converting enzyme appears normal.
    Sep. 2020, American journal of ophthalmology case reports, 19, 100796 - 100796, English, International magazine
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • Ryouhei Komaki, Norio Chihara, Atsushi Hara, Satoshi Fujisawa, Naokazu Muramae, Kazutaka Nakasone, Takehiro Ueda, Kenji Sekiguchi, Riki Matsumoto
    Corresponding, Wiley, Jul. 2020, Neurology and Clinical Neuroscience
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Norio Chihara
    Wiley, May 2020, Clinical and Experimental Neuroimmunology
    [Refereed]
    Scientific journal

  • Yoshiki Takai, Tatsuro Misu, Kimihiko Kaneko, Norio Chihara, Koichi Narikawa, Satoko Tsuchida, Hiroya Nishida, Takashi Komori, Morinobu Seki, Teppei Komatsu, Kiyotaka Nakamagoe, Toshimasa Ikeda, Mari Yoshida, Toshiyuki Takahashi, Hirohiko Ono, Shuhei Nishiyama, Hiroshi Kuroda, Ichiro Nakashima, Hiroyoshi Suzuki, Monika Bradl, Hans Lassmann, Kazuo Fujihara, Masashi Aoki
    Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9-64), and the median interval from attack to biopsy was 1 month (range 0.5-96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.
    May 2020, Brain : a journal of neurology, 143(5) (5), 1431 - 1446, English, International magazine
    [Refereed]
    Scientific journal

  • 千原 典夫
    (株)南江堂, Apr. 2020, 内科, 125(4) (4), 894 - 894, Japanese
    [Refereed][Invited]

  • 千原 典夫
    (株)南江堂, Apr. 2020, 内科, 125(4) (4), 896 - 896, Japanese
    [Refereed][Invited]

  • 【知らずにすまない神経眼科疾患!】抗GQ1b抗体症候群
    赤谷 律, 千原 典夫
    1950年代にFisherが報告した急性発症の外眼筋麻痺・運動失調・腱反射消失といった臨床的特徴を呈する症候群は、これとは別にBickerstaffにより報告された外眼筋麻痺・運動失調・意識障害などを呈する症候群とともに血清抗ガングリオシドGQ1b IgG抗体の関与が明らかとなり、一連の疾患として認識されるようになった。フィッシャー症候群(FS)、ビッカースタッフ脳幹脳炎(BBE)と称されるこれら両疾患は、同じく抗ガングリオシド抗体の関与が知られるギラン・バレー症候群(GBS)の亜型と位置づけられており、ヒト神経系におけるガングリオシドGQ1bの発現・局在が特異な臨床症状を規定していると考えられている。近年、FSやBBEの臨床像の多様性や抗GQ1b抗体陰性FS症例における、ガングリオシド複合体抗体や、Ca2+依存性GQ1b抗体の発見など新たな知見が集積しつつある。(著者抄録)
    (株)全日本病院出版会, Feb. 2020, OCULISTA, (83) (83), 20 - 27, Japanese
    [Invited]

  • CD4+T細胞における共抑制分子の発現制御機構
    千原 典夫
    鳥居薬品(株), Oct. 2019, 感染・炎症・免疫, 49(2) (2), 133 - 135, Japanese
    [Invited]

  • Kenji Sekiguchi, Rei Hashimoto, Yoshikatsu Noda, Hisatsugu Tachibana, Yoshihisa Otsuka, Norio Chihara, Yusuke Shiraishi, Takaaki Inoue, Takehiro Ueda
    Oct. 2019, Muscle & nerve, 60(4) (4), E23-E25 - E25, English, International magazine
    [Refereed]
    Scientific journal

  • Ritsu Akatani, Norio Chihara, Hisatsugu Tachibana, Shusuke Koto, Hisatomo Kowa, Fumio Kanda, Riki Matsumoto, Tatsushi Toda
    OBJECTIVES: Cognitive impairment is a common symptom affecting daily activities of the patients with multiple sclerosis (MS). Various cognitive evaluation tests are available, yet most of them are complex and time-consuming to perform in outpatient clinics. In this study, we aimed to validate a Japanese version of the Guy's Neurological Disability Scale (GNDS) as a user-friendly tool to evaluate comprehensive disabilities in MS including cognitive function. METHODS: Questions of the GNDS were translated into Japanese and named GNDS-J. Forty-four patients were examined by the Expanded Disability Status Scale (EDSS), the Paced Auditory Serial Addition Test (PASAT), the Symbol Digit Modalities Test (SDMT), the vitality scale, and the GNDS-J in the same time at remission state. RESULTS: The GNDS-J scores correlated with the EDSS scores(r = 0.61), and inversely correlated with the PASAT2/1(r=-0.56/-0.49) scores and the SDMT scores (r=-0.68), whereas the GNDS-J did not show any correlation with the vitality scale. Furthermore, eleven patients were evaluated over 5 years for changes in these scores. Eight out of 11 patients had exacerbated GNDS, and all of these patients experienced clinical relapse during this period. CONCLUSION: The GNDS-J is a valid tool to perform in outpatient clinics, which could provide a comprehensive scale for evaluating symptoms of MS, thus the disease activity by repeated measure.
    Corresponding, Oct. 2019, Multiple sclerosis and related disorders, 35, 272 - 275, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Norio Chihara, Riki Matsumoto, Takashi Yamamura
    Neuroimmunological disorders are diseases of the nervous system, wherein the immune system contributes to tissue injury and repair. Autoantibodies are useful biomarkers for the diagnosis of neuroimmunological disorders and evaluating disease activity. Emerging evidence indicates that several autoantibodies are associated with neuroimmunological diseases. While the differential diagnostic process based on the positivity of autoantibodies has been established, the mechanisms underlying the production of these autoantibodies still need to be investigated. Autoantibodies are not necessarily pathogenic, and some are involved in immune regulation. Autoantibody-producing plasmablasts are involved in both pathogenicity and immune regulation of diseases. Thus, comparisons between these pathogenic and regulatory plasmablasts may give us clues understanding the machinery of autoantibody-related neuroimmunological diseases. Moreover, elucidating these mechanisms may allow the development of new immune-modulatory therapies to facilitate regulatory B cell function in neuroimmunological diseases. To this end, herein the roles of plasmablasts in neuroimmunological disorders are discussed.
    Sep. 2019, Immunological medicine, 42(3) (3), 103 - 107, English, International magazine
    [Refereed][Invited]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ritsu Akatani, Norio Chihara, Kimitaka Katanazaka, Takehiro Ueda, Kenji Sekiguchi, Riki Matsumoto
    A 42-year-old woman diagnosed with multiple sclerosis (MS) at the age of 37 was initially treated with interferon-β IM. The frequency of clinical relapses was twice in 4 years. At the age of 41, due to difficulty in administering muscle injections, an oral medication fingolimod was started. However, it was discontinued after a month due to decreased lymphocyte count, following which natalizumab was administered. The number of relapses increased 3 times in eleven months, and the number of T2 lesions on the MRI increased from 12 to 23. Natalizumab was discontinued because the test for the anti-natalizumab antibody was positive. It was suspected that both, the rebound syndrome caused by fingolimod cessation and the drug neutralization by anti-natalizumab antibodies, were associated with the exacerbation of disease activity. Thus, careful attention should be paid to potential occurrence of these events post switching between disease-modifying drugs for treating MS with high activity.
    Corresponding, Aug. 2019, Rinsho shinkeigaku = Clinical neurology, 59(8) (8), 536 - 540, Japanese, Domestic magazine
    [Refereed]
    Scientific journal

  • 赤谷 律, 千原 典夫, 刀坂 公崇, 上田 健博, 関口 兼司, 松本 理器
    42歳女性。37歳時に多発性硬化症(multiple sclerosis;MS)と診断。インターフェロンβ筋注薬の投与が開始され、再発頻度は4年間で2回であった。注射製剤への抵抗感が強く、41歳時にフィンゴリモドへ変更したが、リンパ球数低下あり約1ヵ月で中止し、ナタリズマブへ変更した。その後、11ヵ月で3回再発を繰り返し、T2病変数は12個から23個まで増加した。抗ナタリズマブ抗体が陽性であったためナタリズマブは中止した。疾患活動性の上昇には抗ナタリズマブ抗体による薬効の減弱やフィンゴリモド中止によるリバウンド現象の関与が疑われた。MS治療薬の変更に際し注意すべき事象の一つと考え報告する。(著者抄録)
    Corresponding, (一社)日本神経学会, Aug. 2019, 臨床神経学, 59(8) (8), 536 - 540, Japanese
    [Refereed]

  • 千原 典夫
    (有)科学評論社, Jun. 2019, 臨床免疫・アレルギー科, 71(6) (6), 555 - 560, Japanese
    [Invited]

  • 千原 典夫, 松本 理器, 山村 隆
    Lead, (株)中外医学社, Jun. 2019, Clinical Neuroscience, 37(6) (6), 744 - 746, Japanese
    [Invited]

  • Huiyuan Zhang, Asaf Madi, Nir Yosef, Norio Chihara, Amit Awasthi, Caroline Pot, Lionel Apetoh, Amitabh Srivastava, Chao Wang, Aviv Regev, Vijay Kuchroo
    Abstract IL-10 produced by CD4 T cells plays an essential role in limiting inflammation and autoimmunity. All T help cell subsets can co-produce IL-10 to mitigate unwanted immunopathology but naïve CD4 T cells can also be directly polarized to IL-10 producing Type 1 regulatory (Tr1) cells by the immunoregulatory cytokine, IL-27. Although several transcription factors (TFs) have been shown to regulate IL-10 expression in different contexts, a comprehensive transcriptional network that induce and maintain IL-10 in various CD4 T cells is lacking. Here we utilized two complementary approaches to systemically study the transcriptional mechanisms driving IL-10 production in T helper cells: 1) We combined novel computational tools with transcriptomic profiling of in-vitro Tr1 cell differentiation at high temporal resolution to build a comprehensive and dynamic transcriptional network that regulates IL-10 production in CD4 T cells. We identified four transcription waves that govern Tr1 differentiation: dynamic early phase, stable early phase, induction phase and maintenance phase. Based on the network analysis, we computationally predicted 78 TFs that regulate different waves and experimentally validated 24 of them using knock-out mice. 2) To identify TFs associated with IL-10 production across T helper cell subsets, we compared RNA-seq data of IL-10+ versus IL-10− compartments of in-vitro differentiated Th1, Th2 and Th17 cells. Using a comprehensive ranking scheme, we identified two TFs that regulates IL-10 production in all helper T cell subsets. Conditional deletion of both the TFs but not either alone with CD4-Cre abolishes IL-10 production from Tr1 cells in vitro and leads to spontaneous colitis in vivo.
    The American Association of Immunologists, May 2019, The Journal of Immunology, 202(1_Supplement) (1_Supplement), 124.14 - 124.14
    [Refereed]
    Scientific journal

  • A. Ho, S. Xiao, A. Madi, N. Chihara, A. Regev, V. Kuchroo
    Elsevier BV, May 2019, Journal of Investigative Dermatology, 139(5) (5), S15 - S15
    [Refereed]
    Scientific journal

  • 千原 典夫
    医歯薬出版(株), May 2019, 医学のあゆみ, 269(7) (7), 549 - 550, Japanese
    [Invited]

  • Perivenous inflammatory demyelination is the prominent pathology in myelin oligodendrocyte glycoprotein antibody-associated disease
    Yoshiki Takai, Misu Tatsuro, Kaneko Kimihiko, Norio Chihara, Kouidhi Narikawa, Satoko Tsuchida, Hiroya Nishida, Takahashi Toshiyuki, Masashi Aoki, Fujihara Kazuo
    Feb. 2019, BRAIN PATHOLOGY, 29, 13
    [Refereed]

  • Norio Chihara, Asaf Madi, Ana C. Anderson, Vijay K. Kuchroo
    Feb. 2019, Clinical and Experimental Neuroimmunology, 10(1) (1), 5 - 6, English
    [Refereed][Invited]
    Scientific journal

  • Perivenous inflammatory demyelination with MOG- dominant myelin loss is a characteristic feature of MOG antibody-associated disease
    Y. Takai, T. Misu, K. Kaneko, N. Chihara, K. Narikawa, S. Tsuchida, H. Nishida, T. Komori, M. Seki, T. Komatsu, K. Nakamagoe, T. Ikeda, M. Yoshida, T. Takahashi, H. Ono, S. Nishiyama, H. Kuroda, I. Nakashima, H. Suzuki, M. Bradl, H. Lassmann, K. Fujihara, M. Aoki
    2019, Multiple Sclerosis Journal, 25(S2) (S2), 93
    [Refereed]
    Scientific journal

  • Yuichiro Yasuda, Tatsuya Nagano, Motoko Tachihara, Norio Chihara, Kanoko Umezawa, Naoko Katsurada, Masatsugu Yamamoto, Kenji Sekiguchi, Kazuyuki Kobayashi, Yoshihiro Nishimura
    We herein report the case of a 39-year-old Japanese female with eosinophilic pneumonia associated with natalizumab. The patient with bronchial asthma had multiple sclerosis and was treated using natalizumab. The patient was referred to our department because of a persistent cough. A chest computed tomography (CT) scan revealed bilateral patchy consolidation surrounded by ground-glass opacity. A bronchoalveolar lavage (BAL) was performed. Eosinophil levels in the BAL fluid were increased and the patient was consequently diagnosed as eosinophilic pneumonia associated with natalizumab. Therefore, natalizumab treatment was discontinued. Subsequent chest CT findings showed a remarkable improvement without any treatment.
    2019, Therapeutics and clinical risk management, 15, 1283 - 1289, English, International magazine
    [Refereed]
    Link to Kobe Univ. Repository (Kernel)

  • Hirotomo Tanaka, Daisuke Yamamoto, Katsu Mizukawa, Akiyasu Kanamori, Norio Chihara, Ryosuke Matsuoka, Shigeo Hara, Takanori Hirose, Takashi Sasayama, Eiji Kohmura
    Nov. 2018, Brain pathology (Zurich, Switzerland), 28(6) (6), 1027 - 1028, English, International magazine
    [Refereed]
    Scientific journal

  • Perivenous inflammatory demyelination with CD4-dominat T cell infiltration is prominent in myelin oligodendrocyte glycoprotein antibody-associated diseas
    Y Takai, T Misu, K Kaneko, N Chihara, K Narikawa, S Tsuchida, H Nishida, S Nishiyama, H Kuroda, T Takahashi, I Nakashima, M Aoki, K Fujihara
    Oct. 2018, 24, 380 - 381
    [Refereed]

  • Atsushi Sudo, Norio Chihara, Yu Takenaka, Tetsu Nakamura, Takehiro Ueda, Kenji Sekiguchi, Tatsushi Toda
    Corresponding, Sep. 2018, Neurology(R) neuroimmunology & neuroinflammation, 5(5) (5), e482, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Norio Chihara, Asaf Madi, Takaaki Kondo, Huiyuan Zhang, Nandini Acharya, Meromit Singer, Jackson Nyman, Nemanja D Marjanovic, Monika S Kowalczyk, Chao Wang, Sema Kurtulus, Travis Law, Yasaman Etminan, James Nevin, Christopher D Buckley, Patrick R Burkett, Jason D Buenrostro, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
    The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer1,2. Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors. We functionally validated two new co-inhibitory receptors, activated protein C receptor (PROCR) and podoplanin (PDPN). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in several physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors PRDM1 and c-MAF as cooperative regulators of the co-inhibitory module, and this was validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies regulators of T cell function with the potential to control autoimmunity and tumour immunity.
    Lead, Jun. 2018, Nature, 558(7710) (7710), 454 - 459, English, International magazine
    [Refereed]
    Scientific journal

  • Norio Chihara
    Multiple exogenous signals received from cell surface molecules or cytokines play a significant role in altering the host immune response. In chronic autoimmune-mediated diseases, such as multiple sclerosis (MS), immune cells, especially T cells, are involved in the long-term pathophysiology. In the past few decades, mechanisms of pathogenic T-cell involvement at the onset or relapse of disease have been highlighted. However, the factors controlling the disease course have yet to be elucidated because of the complexity of tissue environmental factors. In contrast, dysfunctional or exhausted T cells have been identified as distinct cell lineages in chronic inflammatory diseases, such as cancer or chronic viral infections that show regulatory T cell phenotypes for example, expressing high levels of co-inhibitory receptors. Regarding cell surface molecule expression, while co-stimulatory molecules promote effector T-cell function, co-inhibitory molecules promote regulatory T-cell function, limiting the inflammatory response. In MS, augmented activation of effector T cells as a result of the impairment of regulatory T-cell function has been implicated. Thus, a comparison between these regulatory T cells in MS and dysfunctional T cells in cancer could provide clues to understand the mechanism of dysregulated T cells, resulting in sustained immune reactions in the long-term disease course of MS. Furthermore, this reveals new immunomodulatory strategies to regain regulatory T-cell function in MS.
    Wiley-Blackwell, Mar. 2018, Clinical and Experimental Neuroimmunology, 9(Supplement S1) (Supplement S1), 20 - 29, English
    [Refereed][Invited]

  • N. Chihara, A. Madi, A. Anderson, A. Regev, V. Kuchroo
    Lead, Elsevier BV, Oct. 2017, Journal of the Neurological Sciences, 381, 531 - 532
    [Refereed]
    Scientific journal

  • Hironobu Endo, Takeshi Uenaka, Wataru Satake, Yutaka Suzuki, Hisatsugu Tachibana, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Taniguchi-Ikeda Mariko, Hisatomo Kowa, Fumio Kanda, Tatsushi Toda
    A 40-year-old Japanese woman presented with slowly progressing parkinsonism in adulthood. She had a history of epilepsy with intellectual disability in childhood. In a head magnetic resonance scan, T2-weighted imaging showed low signal intensity areas in the globus pallidus and the substantia nigra; T1-weighted imaging showed a halo in the nigra. Because the patient's symptoms and history were similar to those of patients with neurodegeneration with brain iron accumulation, we ran an exome analysis to investigate neurodegeneration with brain iron accumulation-associated genes. We identified a c.700 C>T (p.Arg 234*) mutation in exon 9 of the WDR45 gene, which had not been reported in Japanese patients with beta-propeller protein-associated neurodegeneration (a neurodegeneration with brain iron accumulation subtype). Sanger sequencing confirmed a heterozygous mutation in this patient that was absent in both her parents, so it was judged to be a de novo nonsense mutation.
    Jul. 2017, Neurology and clinical neuroscience, 5(4) (4), 131 - 133, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • A. Ho, A. Madi, N. Chihara, A. Regev, V. Kuchroo
    Elsevier BV, May 2017, Journal of Investigative Dermatology, 137(5) (5), S8 - S8
    [Refereed]
    Scientific journal

  • Yasuhiro Kishi, Takaaki Kondo, Sheng Xiao, Nir Yosef, Jellert Gaublomme, Chuan Wu, Chao Wang, Norio Chihara, Aviv Regev, Nicole Joller, Vijay K Kuchroo
    Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORγt, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation. CD4+ T cells from PROCR low expressor mutant mice readily differentiated into Th17 cells, whereas addition of the PROCR ligand, activated protein C, inhibited Th17 differentiation in vitro. In addition, PROCR acted as a negative regulator of Th17 pathogenicity in that it down-regulated expression of several pathogenic signature genes, including IL-1 and IL-23 receptors. Furthermore, T cell-specific deficiency of PROCR resulted in the exacerbation of experimental autoimmune encephalomyelitis (EAE) and higher frequencies of Th17 cell in vivo, indicating that PROCR also inhibits pathogenicity of Th17 cells in vivo. PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells.
    Oct. 2016, The Journal of experimental medicine, 213(11) (11), 2489 - 2501, English, International magazine
    [Refereed]
    Scientific journal

  • Mechanisms driving co-inhibitory receptor expression on T cells
    N Chihara, A Madi, T Kondo, M Singer, H Zhang, C Wang, S Kurtulus, P Burke, A Regev, A Anderson, V Kuchroo
    Lead, Aug. 2016, EUROPEAN JOURNAL OF IMMUNOLOGY, 46, 792 - 793
    [Refereed]

  • 炎症免疫 / ボストン留学便り
    Chihara Norio
    先端医学社, May 2016, Japanese
    [Invited]

  • Norio Chihara, Asaf Madi, Katarzyna Karwacz, Amit Awasthi, Vijay K Kuchroo
    Regulatory T cell-mediated suppression serves as a pivotal mechanism of negative regulation of immune-mediated inflammation. Type 1 regulatory T cells (Tr1 cells) are an important subset of CD4+ T cells that prevent excessive inflammatory responses and maintain immune tolerance. The anti-inflammatory role of Tr1 cells is mediated in part by their production of interleukin 10 (IL-10), which dampens the function of both antigen-presenting cells and antigen-specific effector T cells. Additionally, Tr1 cells can kill effector and myeloid cells through the perforin-granzyme B pathway. Adoptive transfer of in vitro differentiated Tr1 cells can be used to suppress autoimmune tissue inflammation in vivo. This unit describes the in vitro stimulation of naïve murine CD4+ T cells using IL-27 to generate IL-10-producing Tr1 cells.
    Lead, Apr. 2016, Current protocols in immunology, 113, 3.27.1-3.27.10 - 3.27.10, English, International magazine
    [Refereed][Invited]
    Scientific journal

  • 疾患からみた細胞表面機能分子(第4回)視神経脊髄炎におけるAQP4
    千原 典夫
    視神経脊髄炎(NMO)は重度の視神経炎と脊髄炎をくり返す中枢神経系の慢性炎症性疾患である。本疾患に対する米国食品医薬品局(FDA)に承認された治療薬はない。抗アクアポリン(AQP)4抗体が疾患特異的なバイオマーカーとして診断に用いられる一方で、数々の研究がこの抗体の病原性について言及している。NMOの病態背景にはAQP4特異的B細胞が抗AQP4抗体を産生するにいたる自己免疫応答があり、その解明がNMOの治療戦略につながると期待される。(著者抄録)
    先端医学社, May 2015, 分子リウマチ治療, 8(2) (2), 96 - 99, Japanese
    [Invited]

  • Sachiko Miyake, Sangwan Kim, Wataru Suda, Kenshiro Oshima, Masakazu Nakamura, Takako Matsuoka, Norio Chihara, Atsuko Tomita, Wakiro Sato, Seok-Won Kim, Hidetoshi Morita, Masahira Hattori, Takashi Yamamura
    The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS.
    2015, PloS one, 10(9) (9), e0137429, English, International magazine
    [Refereed]
    Scientific journal

  • Hironobu Endo, Norio Chihara, Kenji Sekiguchi M D, Hisatomo Kowa, Fumio Kanda, Tatsushi Toda
    The patient was a 46-year-old woman having a history of multiple sclerosis (MS) for 14 years. She had been treated with interferon β-1b since 2001, but discontinued because of psychiatric problems in 2006. Thereafter relapses were observed 1-2 times a year, and EDSS became 2.5 to 6.5. In April 2012, relapse of MS was noticed and the patient received introduction of fingolimod (FTY) after methylprednisolone (mPSL) pulse therapy. Twenty days later, dysarthria and lower limb weakness were appeared. Brain MRI showed more than 20 several millimeter Gd enhanced lesions in periventricular white matter, juxta-cortical white matter, and cerebellum. Careful determination and observation are required upon the FTY administration into the MS with high frequency of relapse.
    2015, Rinsho shinkeigaku = Clinical neurology, 55(6) (6), 417 - 20, Japanese, Domestic magazine
    [Refereed]
    Scientific journal

  • Wakiro Sato, Toshimasa Aranami, Norio Chihara, Ryotaro Ikeguchi, Tomoko Okamoto, Takashi Yamamura
    ELSEVIER SCIENCE BV, Oct. 2014, JOURNAL OF NEUROIMMUNOLOGY, 275(1-2) (1-2), 209 - 209, English
    [Refereed]

  • Plasmablasts as AQP4-Ab producers in the pathogenesis of neuromyelitis optica
    N Chihara, T Aranami, S Oki, T Matsuoka, M Nakamura, T Okamoto, M Murata, T Toda, S Miyake, T Yamamura
    Lead, Sep. 2014, MULTIPLE SCLEROSIS JOURNAL, 20, 345 - 346
    [Refereed]

  • Masakazu Nakamura, Takako Matsuoka, Norio Chihara, Sachiko Miyake, Wakiro Sato, Manabu Araki, Tomoko Okamoto, Youwei Lin, Masafumi Ogawa, Miho Murata, Toshimasa Aranami, Takashi Yamamura
    BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS. METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod. CONCLUSIONS: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.
    Sep. 2014, Multiple sclerosis (Houndmills, Basingstoke, England), 20(10) (10), 1371 - 80, English, International magazine
    [Refereed]
    Scientific journal

  • 千原 典夫
    南江堂, Jun. 2013, 内科, 111(6) (6), 1407 - 1407, Japanese
    [Invited]

  • 千原 典夫
    南江堂, Jun. 2013, 内科, 111(6) (6), 1405 - 1405, Japanese
    [Invited]

  • Norio Chihara, Toshimasa Aranami, Shinji Oki, Takako Matsuoka, Masakazu Nakamura, Hitaru Kishida, Kazumasa Yokoyama, Yoshiyuki Kuroiwa, Nobutaka Hattori, Tomoko Okamoto, Miho Murata, Tatsushi Toda, Sachiko Miyake, Takashi Yamamura
    Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4. Here, we demonstrate that CD138(+)HLA-DR(+) plasmablasts, a subset of IgG-producing cells, are increased in the peripheral blood and are enriched among the cerebrospinal fluid (CSF) lymphocytes during the relapse of neuromyelitis optica. Notably, these CD138(+)HLA-DR(+) plasmablasts overexpress CXCR3, whose ligands are present in the cerebrospinal fluid during the relapse of neuromyelitis optica. These results led us to speculate that plasmablasts producing anti-aquaporin 4 autoantibodies might traffic toward the central nervous system (CNS). Furthermore, we performed single-cell sorting of plasmablasts from peripheral blood and CSF samples from NMO and sequenced the complementarity-determining regions (CDRs) of the IgG heavy chain expressed by the sorted plasmablast clones. There were high frequencies of mutations in the CDRs compared with framework regions, indicating that these plasmablast clones would represent a post-germinal center B-cell lineage. Consistent with the preceding results, the plasmablast clones from the peripheral blood shared the same CDR sequences with the clones from the CSF. These results indicate that IgG-producing plasmablasts, which are guided by helper T-cells, may migrate from the peripheral blood preferentially to the CSF. Since migratory plasmablasts could be involved in the inflammatory pathology of NMO, the B-cell subset and their migration might be an attractive therapeutic target.
    Lead, 2013, PloS one, 8(12) (12), e83036, English, International magazine
    [Refereed]
    Scientific journal

  • Toshiyuki Yamamoto, Norio Chihara, Madoka Mori-Yoshimura, Miho Murata
    A 47-year-old woman with dysphagia and ptosis gradually developed dysarthria and muscular weakness. Magnetic resonance imaging, testing for anti acetylcholine receptor antibodies, edrophonium chloride (EC) test, and electrophysiologic test revealed no abnormalities. A psychogenic reaction was suspected. Four months after disease onset, the patient presented to our hospital. In videofluoroscopic examination of swallowing (VF), there was no aspiration for swallowing of either liquid or soft food. It revealed, however, poor pharyngeal constriction, no epiglottis inversion, repeated swallowing movements, and large amounts of pharyngeal residue. Videofluoroscopic examination of swallowing after an intravenous injection of 10 mg EC showed improvements in all above observations; particularly, it was clear when swallowing soft food. Furthermore, the anti muscle-specific kinase (MuSK) antibody titer was elevated, and anti-MuSK antibody positive myasthenia gravis (MuSK-MG) was diagnosed. Thus VF during EC test may be helpful in diagnosing MuSK-MG in patients with dysphagia. (C) 2012 Elsevier Inc. All rights reserved.
    W B SAUNDERS CO-ELSEVIER INC, Nov. 2012, AMERICAN JOURNAL OF OTOLARYNGOLOGY, 33(6) (6), 758 - 761, English
    [Refereed]
    Scientific journal

  • 多発性硬化症および関連疾患におけるIL-6の役割
    千原 典夫, 山村 隆
    多発性硬化症(MS)は中枢神経の慢性炎症性疾患で、代表的な自己免疫疾患である。これまで自己反応性T細胞やB細胞の介在する免疫炎症病態が詳細に解析されており、さまざまな炎症性サイトカインやケモカインの関与が検証されている。MSの臨床・病理像は多彩であるが、近年になって抗アクアポリン4自己抗体陽性の症例の存在することがわかり、視神経脊髄炎(NMO)と診断し独立させるようになった。免疫調整薬であるインターフェロンβ(IFN-β)は約半数のMSにおいて寛解維持効果を示すが、残りの症例およびNMOにおいては無効である。IFN-βに反応しないMSとNMOの治療が臨床的には大きな問題になっている。NMO患者髄液ではインターロイキン6(IL-6)の上昇が報告されているが、IFN-βノンレスポンダーにおいても、IL-6が重要な役割を果たす可能性が推測されている。IL-6はMS/NMOで重要なTh17細胞の分化誘導に重要であり、IL-6シグナル阻害によるTh17細胞誘導抑制は、MS/NMOの新たな治療戦略となりうる。一方、IL-6は中枢神経内においては神経保護作用と神経変性促進作用の両者を有しており、そのシグナルは精密に調節されている。本稿では、MSとその関連疾患NMOを取り上げ、その病態とIL-6の役割および抗IL-6受容体抗体による治療戦略について最近の知見をもとに概説する。(著者抄録)
    Lead, 鳥居薬品(株), Apr. 2012, 感染・炎症・免疫, 42(1) (1), 12 - 19, Japanese
    [Invited]

  • 神経内科学 視神経脊髄炎(NMO)における自己抗体産生細胞
    千原 典夫, 山村 隆
    Lead, 医歯薬出版(株), Feb. 2012, 医学のあゆみ, 240(6) (6), 534 - 535, Japanese
    [Invited]

  • 【ここまでわかった自己免疫疾患】各論 そのほかの自己免疫疾患 多発性硬化症・視神経脊髄炎
    千原 典夫, 山村 隆
    中枢神経の炎症性自己免疫疾患の代表である多発性硬化症(MS)と視神経脊髄炎(NMO)では,T細胞やB細胞の介在する炎症病態が詳細に解析され,新しい治療法の開発につながる研究成果が挙がっている.中枢神経組織は通常血液脳関門(BBB)によって保護されているが,一度,神経細胞が障害されると自己再生能に乏しいために,徐々に神経脱落症状が蓄積する.MSやNMOの自己免疫病態を考えるうえで,標的臓器である中枢神経の特殊性を考慮しなければならない.一方で,血液リンパ球を用いた解析は次々に新しい知見を生んでおり,他の自己免疫疾患の研究にも影響を与えている.本稿では,MSおよびNMOにおけるその病態の特徴や両者の違いについて最新の知見を紹介する.(著者抄録)
    Lead, (株)医学書院, Oct. 2011, 臨床検査, 55(11) (11), 1241 - 1248, Japanese
    [Invited]

  • Yoko Sunami, Keizo Sugaya, Norio Chihara, Yu-ichi Goto, Shiro Matsubara
    We present a Japanese family suffering from mitochondrial encephalomyopathy associated with a T-to-C transition at mitochondrial DNA (mtDNA) nucleotide position 3291. Clinical manifestations of the patients include cerebellar ataxia with myopathy, recurrent headache, and myoclonus and epilepsy. The phenotypic variation among the affected members of a single family and the mutational analysis showing maternal inheritance in a heteroplasmic fashion are consistent with well-recognized phenomena associated with many pathogenic point mutations of mtDNA tRNA genes. The 3291 mutation is a rare mtDNA mutation whose clinical presentation had only been reported in three sporadic cases. This is the first report of a family segregating the 3291 mutation with multigenerational matrilinear recurrence of mitochondrial encephalopathy. Our findings provide conclusive evidence for the pathogenicity of the 3291T > C mutation in mtDNA and its characteristic clinical heterogeneity.
    Oct. 2011, Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 32(5) (5), 861 - 4, English, International magazine
    [Refereed]

  • 廣實 真弓, 森 まどか, 千原 典夫, 山本 敏之
    口唇閉鎖不全と舌尖音、奥舌音の構音のしにくさを訴えた抗MuSK抗体陽性重症筋無力症患者(48歳、女)に対し、プレドニゾロン治療前後に定量的な評価としてオーラル・ディアドコキネシスを実施した。/ka/は1ヵ月の治療後改善がみられ、/pa/、/ta/は変化がなかった。治療開始1年後/ka/、/ta/は正常だったが、/pa/は増悪した。治療開始時の重症度から治療効果を予測することは困難だった。(著者抄録)
    日本コミュニケーション障害学会, Aug. 2011, コミュニケーション障害学, 28(2) (2), 60 - 65, Japanese
    [Refereed]

  • Lara Sanvito, Atsuko Tomita, Norio Chihara, Tomoko Okamoto, Youwei Lin, Masafumi Ogawa, Bruno Gran, Toshimasa Aranami, Takashi Yamamura
    Interferon-β (IFN-β) is known to expand regulatory CD56(bright) natural killer (NK) cells in multiple sclerosis (MS). In this cross-sectional study we show that MS patients treated with IFN-β alone or in combination with low-dose prednisolone displayed increased proportion of all NK cell subsets in the active phase of the cell cycle (Ki-67+). There was no difference in NK cell apoptosis markers. In vitro experiments showed that both IFN-β and IFN-β in combination with corticosteroids increased the proportion of Ki-67(+) NK cells. This study, although limited, shows that treatment with IFN-β affects NK cell cycle without altering NK cell apoptosis in MS patients.
    Jul. 2011, Journal of neuroimmunology, 236(1-2) (1-2), 111 - 7, English, International magazine
    [Refereed]

  • Norio Chihara, Toshimasa Aranami, Wakiro Sato, Yusei Miyazaki, Sachiko Miyake, Tomoko Okamoto, Masafumi Ogawa, Tatsushi Toda, Takashi Yamamura
    Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19(int)CD27(high)CD38(high)CD180(-) phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse. We also demonstrate that interleukin 6 (IL-6), shown to be increased in NMO, enhanced the survival of PB as well as their AQP4-Ab secretion, whereas the blockade of IL-6 receptor (IL-6R) signaling by anti-IL-6R antibody reduced the survival of PB in vitro. These results indicate that the IL-6-dependent B-cell subpopulation is involved in the pathogenesis of NMO, thereby providing a therapeutic strategy for targeting IL-6R signaling.
    Lead, Mar. 2011, Proceedings of the National Academy of Sciences of the United States of America, 108(9) (9), 3701 - 6, English, International magazine
    [Refereed]
    Scientific journal

  • 【分子マーカーの基礎と臨床】神経疾患と分子マーカー 多発性硬化症
    千原 典夫, 山村 隆
    Lead, (株)中外医学社, Dec. 2010, Clinical Neuroscience, 28(12) (12), 1396 - 1399, Japanese
    [Invited]

  • 【慢性炎症と疾患 病態解明と治療の新展開】病態と治療 神経疾患と炎症 多発性硬化症を中心に
    千原 典夫, 山村 隆
    慢性炎症の役割がさまざまな神経疾患で推察されている.中でも多発性硬化症で代表される免疫性神経疾患では,T細胞やB細胞の介在する炎症病態がかなり詳細に解析されている.神経組織は血液組織関門により保護されているが,一方では神経細胞には十分な自己再生能がなく,その障害機序の解明と治療法の開発にはさまざまな因子を考慮しなければならない.本稿では多発性硬化症を中心に,炎症の介在する神経障害の機序や治療戦略について,最新の知見を紹介する.(著者抄録)
    Lead, (株)最新医学社, Nov. 2010, 最新医学, 65(11) (11), 2390 - 2395, Japanese
    [Invited]

  • Plasma cell-like B cells produce aquaporin4 autoantibody in neuromyelitis optica
    Norio Chihara, Toshimasa Aranami, Wakiro Sato, Yusei Miyazaki, Sachiko Miyake, Tomoko Okamoto, Masafumi Ogawa, Tatsushi Toda, Takashi Yamamura
    Lead, Oct. 2010, JOURNAL OF NEUROIMMUNOLOGY, 228(1-2) (1-2), 160 - 161
    [Refereed]

  • Y.F. Furusawa, M.M. Mori, N.C. Chihara, Y.M. Murata, E.F. Endo, T.O. Okamoto, C.S. Sakamoto, M.W. Wakita, Y.K. Kobayashi, Y.O. Oya, H.N. Nakamura, I.N. Nonaka, M.M. Murata
    Elsevier BV, Oct. 2010, Neuromuscular Disorders, 20(9-10) (9-10), 674 - 674
    [Refereed]
    Scientific journal

  • Yoshiko Murata, Tomoko Okamoto, Yoshiyuki Kondo, Norio Chihara, Yoshihiko Furusawa, Miho Murata
    A 41-year-old man with multiple motor neuropathy developed weakness of the left hand at the age of 35 years. The weakness gradually progressed to his right hand. High-dose intravenous immunoglobulin (IVIg) therapy (0.4 g/kg for 5 consecutive days) improved the muscle weakness in the hands but led to the development of generalized severe pompholyx that spread to the skin over the entire body. Because muscle weakness of the hands worsened several months after IVIg therapy, we attempted another course of IVIg therapy. However, anti-allergic agents and oral corticosteroids did not suppress the pompholyx induced by the high-dose IVIg. Hence, the treatment was switched to low-dose immunoglobulin therapy (0.4 g/kg for one day) once every month. After more than 8 months of low-dose therapy, only mild form of pompholyx remained and the muscle strength was maintained without further deterioration.
    Societas Neurologica Japonica, 2010, Clinical Neurology, 50(8) (8), 561 - 565, Japanese
    [Refereed]
    Scientific journal

  • 千原 典夫, 山本 敏之, 林 幼緯, 塚本 忠, 小川 雅文, 村田 美穂
    パーキンソン病の82歳女性。66歳から高度の脊柱後彎。82歳から体幹屈曲が悪化し、易転倒が出現。Levodopa 100mg/carbidopa 10mg合剤2錠を空腹時に内服後4時間までの評価では、レボドパ血中濃度は二峰性に推移し、濃度変化に遅れてパーキンソニズムが変動した。体幹屈曲は変化なかった。食道造影と上部消化管内視鏡で食道裂孔ヘルニアと食道の蛇行をみとめ、食道での薬剤通過障害がうたがわれた。同量の薬剤を、飲水量を増やして内服し、内服後、体幹を伸展させた。レボドパ血中濃度は一峰性になり、ピーク値は上昇し、体幹屈曲とパーキンソニズムが改善した。体幹の姿勢異常がレボドパの吸収に影響していたと考えられた。(著者抄録)
    Lead, (一社)日本神経学会, Aug. 2009, 臨床神経学, 49(8) (8), 493 - 496, Japanese
    [Refereed]

  • Fumi Takemoto, Norio Chihara, Naoki Sawa, Junichi Hoshino, Masayuki Yamanouchi, Noriko Hayami, Eiko Hasegawa, Tatsuya Suwabe, Shohei Nakanishi, Michiro Nakamura, Haruo Mitani, Yoshifumi Ubara, Kenmei Takaichi, Minoru Ohno
    Aug. 2009, Kidney international, 76(4) (4), 467 - 467, English, International magazine
    [Refereed]

  • Norio Chihara, Toshiyuki Yamamoto, Youwei Lin, Tadashi Tsukamoto, Masafumi Ogawa, Miho Murata
    An 82 year-old woman with Parkinson's disease complained of a tendency to fall. She has had an extensive kyphosis since she was 66 years old. Over the last 6 months, she has repeatedly fallen. Even though she took anti-parkisonian drugs, she had also developed camptocormia. Her plasma levodopa concentration was analyzed for 4 hrs after administrating an oral dose of levodopa (200 mg) plus carbidopa (20 mg) at the time of fasting. The change in the plasma levodopa concentration showed bimodal peaks. The physical symptoms depended on the plasma concentration and improved twice. Esophageal tortuosity and esophageal hiatal hernia were detected by esophagography and upper gastric endoscopy. Such physical symptoms were speculated to have been caused by the transit disturbance of the drug in the gastrointestinal duct. During a second analysis of the plasma levodopa concentration, the patient was instructed to keep extending her back after consuming the same dose of drugs but with a greater amount of water than in the first analysis. A single and a higher peak were observed for the plasma levodopa concentration, and the physical symptoms, including camptocormia and parkinsonism, were improved. Hunched posture could influence the absorption of antiparkinsonian drugs.
    Lead, Societas Neurologica Japonica, 2009, Clinical Neurology, 49(8) (8), 493 - 496, Japanese
    [Refereed]
    Scientific journal

  • 千原 典夫
    ＜Point＞(1)まず、ベットサイドに行く(2)意識障害の有無を確認し、せん妄を見極める(3)鎮静に眠剤系(ベンゾジアゼピン系)を用いない(著者抄録)
    Lead, 羊土社, May 2008, レジデントノート, 10(2) (2), 235 - 240, Japanese
    [Invited]

  • Norio Chihara, Yasuji Arase, Fumitaka Suzuki, Yoshiyuki Suzuki, Masahiro Kobayashi, Norio Akuta, Tetsuya Hosaka, Hitomi Sezaki, Hiromi Yatsuji, Yusuke Kawamura, Mariko Kobayashi, Sachiyo Watahiki, Kenji Ikeda, Hiromitsu Kumada
    We present a case report of a Japanese patient who showed prolonged infection after acute hepatitis B with genotype H. The patient was a 60-year-old man who underwent an annual health care check every year for several years and was never pointed out to have any liver damage, and markers for hepatitis B and C were negative. He was found to be positive for hepatitis B surface antigen (HBsAg) at his health care check in December 2005. After one month, he had an elevated aminotransferase level with hepatitis B e antigen and a high level of serum HBV DNA. He was diagnosed as having acute hepatitis B. On HBV genotype, he had genotype H by the direct sequence method, and he was given a 100 mg of lamivudine daily. However, his acute hepatitis tended to go toward prolonged infection. After two months, he was treated with interferon daily for 28 days. He had negative HBsAg in August 2006. Genotype H, the newest type of hepatitis B, could be the type which shows a poor response to lamivudine. The present paper is the first report, describing the clinical course of acute hepatitis B with genotype H from onset to remission.
    Lead, 2007, Internal medicine (Tokyo, Japan), 46(22) (22), 1847 - 51, English, Domestic magazine
    [Refereed]

■ MISC
  • Human Immunology 疾患理解から治療へ 多発性硬化症における脳脊髄液T細胞のケモカイン受容体解析
    佐藤 和貴郎, 荒浪 利昌, 冨田 敦子, 千原 典夫, 岡本 智子, 林 幼偉, 村田 美穂, 三宅 幸子, 山村 隆
    日本神経免疫学会, Nov. 2013, 神経免疫学, 18(1) (1), 68 - 68, Japanese

  • MS/NMO 視神経脊髄炎(NMO)におけるB細胞の役割について
    千原 典夫, 佐藤 和貴郎, 荒浪 利昌, 宮崎 雄生, 三宅 幸子, 岡本 智子, 小川 雅文, 山村 隆
    日本神経免疫学会, Mar. 2010, 日本神経免疫学会学術集会抄録集, 22回, 40 - 40, Japanese

■ Books And Other Publications
  • 多発性硬化症(MS)診療のすべて
    山村 隆, 千原 典夫ら
    千原 典夫, 山村 隆, 「視神経脊髄炎(NMO)の治療」, 診断と治療社, pp181-187, 2013 千原 典夫, 「tumefactive MS」, 診断と治療社, pp24-25, 2013 千原 典夫, 「MSとワクチン」, 診断と治療社, pp41-42, 2013, 診断と治療社, May 2012, Japanese, ISBN: 9784787818188

■ Lectures, oral presentations, etc.
  • 側脳室周囲に造影効果病変を伴った視神経脊髄炎スペクトラム障害(NMOSD)の一例
    久後 啓介, 杉澤 良介, 渡邊 有史, 的場 健人, 古東 秀介, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Mar. 2024, Japanese, (一社)日本神経学会

  • 同側顔面および上肢の感覚障害をきたした後脊髄動脈領域梗塞の一例
    坂東 美樹, 芦崎 太一朗, 橋本 黎, 的場 健人, 古東 秀介, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Mar. 2024, Japanese, (一社)日本神経学会

  • The role of IL-6 in NMOSD: pathogenesis and therapeutic implication
    Norio Chihara
    2023 Annual Meeting of the Taiwan Neuroimmunology Medical Society, Dec. 2023
    [Invited]

  • Clinical Experience with Satralizumab and Steroid Tapering in the Treatment of NMOSD
    Norio Chihara
    2023 TNMS Dinner Symposium, Dec. 2023
    [Invited]

  • 多発性硬化症と視神経脊髄炎の病態と新たな治療戦略
    千原 典夫
    日本臨床免疫学会総会プログラム・抄録集, Oct. 2023, Japanese, (一社)日本臨床免疫学会

  • 日本人多発性硬化症患者における疫学調査 日本人集団解析結果
    磯部 紀子, 深澤 俊行, 富沢 雄二, 大橋 高志, 櫻井 謙三, 千原 典夫, 中村 優理, 野原 千洋子, 佐藤 弥生, 神田 三智弘, 吉良 潤一
    神経治療学, Oct. 2023, Japanese, (一社)日本神経治療学会

  • 難治性神経免疫疾患 多発性硬化症におけるCD8陽性T細胞の抑制性遺伝子プログラムの解明
    千原 典夫, 古東 秀介, 赤谷 律, 辻 麻人, 刀坂 公崇, 西居 正汰, 松本 理器
    日本臨床免疫学会総会プログラム・抄録集, Oct. 2023, Japanese, (一社)日本臨床免疫学会

  • てんかん重積を契機として診断された神経梅毒の一例
    加藤 拓実, 十河 正弥, 芦崎 太一朗, 橋本 黎, 的場 健人, 岡山 公宣, 古東 秀介, 千原 典夫, 関口 兼司, 濱口 浩敏, 松本 理器
    臨床神経学, Oct. 2023, Japanese, (一社)日本神経学会

  • 循環濾胞性T細胞の偏倚とplasmablastsの増加が自己免疫性てんかんを特徴づける
    原 敦, 千原 典夫, 赤谷 律, 錦織 隆成, 辻 麻人, 吉村 元, 川本 未知, 大塚 喜久, 影山 恭史, 近藤 誉之, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • 膜型BAFFを発現する単球は活性化によって抑制性受容体発現を低下させる
    田川 友花, 赤谷 律, 千原 典夫, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • Pros & Cons.2023年版視神経脊髄炎スペクトラム診療を考える Cons「#1.NMOSDには初発から生物学的製剤を使用すべきではない:病態機序・副作用の視点から」
    千原 典夫
    神経免疫学, Sep. 2023, Japanese, (一社)日本神経免疫学会
    [Invited]

  • 敗血症に伴う精神障害の回復にはCD4+T細胞が重要である
    齋藤 雅史, 大野 雄康, 山下 公大, 関 恒慶, 千原 典夫, 小谷 穣治
    神経免疫学, Sep. 2023, Japanese, (一社)日本神経免疫学会

  • 循環濾胞性T細胞の偏倚とplasmablastsの増加が自己免疫性てんかんを特徴づける
    原 敦, 千原 典夫, 赤谷 律, 錦織 隆成, 坂本 光弘, 吉村 元, 川本 未知, 大塚 喜久, 影山 恭史, 近藤 誉之
    てんかん研究, Sep. 2023, Japanese, (一社)日本てんかん学会

  • 非けいれん性てんかん重積における周期性放電の電気生理的転帰関連因子の探索
    甲田 一馬, 十河 正弥, 木村 正夢嶺, 森本 耕平, 的場 健人, 古東 秀介, 千原 典夫, 関口 兼司, 影山 恭史, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • 周期性放電に伴い陰性ミオクローヌスが出現したてんかん重積2例の神経生理学的検討
    芦崎 太一朗, 十河 正弥, 甲田 一馬, 木村 正夢嶺, 森本 耕平, 的場 健人, 千原 典夫, 関口 兼司, 影山 恭史, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • 結節性硬化症における皮質結節の性状とてんかん性放電の関連
    木村 正夢嶺, 十河 正弥, 甲田 一馬, 森本 耕平, 的場 健人, 古東 秀介, 千原 典夫, 関口 兼司, 藤本 陽介, 千葉 公嗣, 永瀬 裕朗, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • 皮膚筋炎として治療されていた顔面肩甲上腕筋ジストロフィー(FSHD)疑いの一例
    権藤 徹郎, 十河 正弥, 中安 翔一, 芦崎 太一朗, 木村 正夢嶺, 的場 健人, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • COVID19を契機にクリーゼに至った重症筋無力症の一例
    鈴木 逸太, 千原 典夫, 岡田 誠央, 宇田 有希, 矢幡 悟大, 武田 涼輔, 的場 俊, 十河 正弥, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • COVID-19後に発症した重症Guillain-Barre症候群の1例
    濱本 実貴, 十河 正弥, 岩本 宗矩, 牧野 愛, 西居 正汰, 吉川 正章, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2023, Japanese, (一社)日本神経学会

  • 多発性硬化症患者脳脊髄液におけるCD8+T細胞上のPD-1発現上昇が良好な長期予後の指標となりうる
    古東 秀介, 千原 典夫, 赤谷 律, 辻 麻人, 刀坂 公崇, 西居 正汰, 的場 健人, 十河 正弥, 関口 兼司, 松本 理器
    神経免疫学, Sep. 2023, Japanese, (一社)日本神経免疫学会

  • 日本人MSにおける神経障害進行指標としてのSDMTの有用性の検証
    城間 京香, 千原 典夫, 赤谷 律, 古東 秀介, 的場 健人, 十河 正弥, 関口 兼司, 松本 理器
    神経免疫学, Sep. 2023, Japanese, (一社)日本神経免疫学会

  • 亜急性の小脳性運動失調から診断されたALK陰性未分化大細胞リンパ腫(ALCL)による傍腫瘍性神経症候群の1例
    矢幡 悟大, 千原 典夫, 岡田 誠央, 北 峻志, 木村 正夢嶺, 武田 涼輔, 的場 健人, 古東 秀介, 十河 正弥, 関口 兼司, 苅田 典生, 松本 理器, 兼平 博史, 佐伯 美紀, 平川 結梨, 松本 咲耶, 北尾 章人, 藥師神 公和
    臨床神経学, Aug. 2023, Japanese, (一社)日本神経学会

  • 脊髄癆で発症した晩期顕性梅毒の36歳男性例
    北 峻志, 十河 正弥, 岡田 誠央, 矢幡 悟大, 武田 涼輔, 的場 健人, 古東 秀介, 千原 典夫, 関口 兼司, 苅田 典生, 松本 理器
    臨床神経学, Aug. 2023, Japanese, (一社)日本神経学会

  • 右前頭葉焦点切除術後に歩行開始で誘発される強直発作が出現した難治性焦点てんかんの一例
    芦崎 太一朗, 十河 正弥, 宇田 有希, 木村 正夢嶺, 的場 健人, 古東 秀介, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Aug. 2023, Japanese, (一社)日本神経学会

  • 帯状回由来の焦点発作を疑った抗ミエリンオリゴデンドロサイト糖蛋白抗体陽性大脳皮質脳炎の2症例
    田中 智子, 十河 正弥, 岡山 公宣, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Jul. 2023, Japanese, (一社)日本神経学会, 感覚発作から焦点意識減損強直発作,ついで焦点起始両側強直間代発作に進展した若年男性の2症例を経験した.発作型は片側上肢の異常感覚から上下肢が伸びる強直姿勢をとり,焦点起始両側強直間代発作に至った.異常感覚や強直姿勢は帯状回皮質への皮質電気刺激で報告があり,感覚発作や焦点意識減損強直発作を認める場合には帯状回由来の発作を疑う必要がある.2例とも頭部MRIで帯状回に異常信号を認め,血液中の抗ミエリンオリゴデンドロサイト糖蛋白(myelin oligodendrocyte glycoprotein,以下MOGと略記)抗体陽性が判明し,抗MOG抗体陽性大脳皮質脳炎と診断した.ステロイド治療が有効だった経過から抗MOG抗体関連疾患による帯状回病変が発作の焦点となったと考えた.(著者抄録)

  • 緩徐進行性の認知機能障害・不随意運動・意識障害を呈した自己免疫性glial fibrillary acidic protein(GFAP)アストロサイトパチーの一例
    土田 愛, 岡山 公宣, 武田 涼輔, 上月 淳, 曽 菲亜, 十河 正弥, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Jun. 2023, Japanese, (一社)日本神経学会

  • SARS-CoV-2ワクチン接種後に発症した神経痛性筋萎縮症の一例
    宇田 有希, 古東 秀介, 渡部 俊介, 北 峻志, 武田 涼輔, 末廣 大知, 的場 健人, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Jun. 2023, Japanese, (一社)日本神経学会

  • けいれんと認知機能低下で発症した軟膜炎を伴う髄膜脳炎の一例
    松野 泰幸, 十河 正弥, 千原 典夫, 藤本 陽介, 児玉 良典, 篠山 隆司, 松本 理器
    臨床神経学, Jun. 2023, Japanese, (一社)日本神経学会

  • 終夜ウェアラブル脳波計測による高齢発症てんかんの神経生理学的研究—Neurophysiological research on late-onset epilepsy using overnight wearable EEG
    松本 理器, 原 敦, 甲田 一馬, 森本 耕平, 的場 健人, 岡山 公宣, 坂本 光弘, 十河 正弥, 千原 典夫, 葛谷 聡, 古和 久朋
    てんかん治療研究振興財団研究年報 = Annual report of the Japan Epilepsy Research Foundation, 2023, Japanese, 大阪 : てんかん治療研究振興財団

  • 帯状疱疹後に神経痛性筋萎縮症を発症した一例の超音波所見
    吉川 正章, 古結 裕之, 上月 惇, 甲田 一馬, 末廣 大知, 渡部 俊介, 岡山 公宣, 野田 佳克, 千原 典夫, 関口 兼司, 松本 理器
    末梢神経, Dec. 2022, Japanese, 日本末梢神経学会

  • IL-6 and its targeting therapy in NMOSD
    Norio Chihara
    14th PACTRIMS congress 2022, Nov. 2022
    [Invited]

  • 終夜ビデオ脳波モニタリングが自己免疫性病態の評価に有用であった焦点てんかんの1例
    刀坂 公崇, 十河 正弥, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Nov. 2022, Japanese, (一社)日本神経学会

  • 髄液胎盤型アルカリフォスファターゼ測定が診断に有用だった脊髄再発germinomaの一例
    田中 智子, 刀坂 公崇, 十河 正弥, 千原 典夫, 上田 健博, 関口 兼司, 木村 英仁, 児玉 良典, 篠山 隆司, 松本 理器
    臨床神経学, Nov. 2022, Japanese, (一社)日本神経学会

  • 焦点感覚発作から焦点意識保持強直発作を呈し帯状回由来の発作を疑った抗MOG抗体陽性大脳皮質脳炎の1例
    田中 智子, 十河 正弥, 岡山 公宣, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Nov. 2022, Japanese, (一社)日本神経学会

  • 臨床免疫領域における臓器・組織特異性 神経免疫学の基礎と新展開
    千原 典夫
    日本臨床免疫学会総会プログラム・抄録集, Oct. 2022, Japanese, (一社)日本臨床免疫学会
    [Invited]

  • 多発性硬化症(MS)の最新治療戦略 多発性硬化症における個別化医療の発展に向けて
    千原 典夫
    神経治療学, Oct. 2022, Japanese, (一社)日本神経治療学会
    [Invited]

  • MOG抗体関連疾患(MOGAD)の臨床と病態 MOGADの病態と治療
    千原 典夫
    神経治療学, Oct. 2022, Japanese, (一社)日本神経治療学会
    [Invited]

  • m.14487T>C変異を認めたLHON plusの一例
    岡山 真由佳, 上田 香織, 千原 典夫, 昭原 郁仁, 奥田 実奈, 高野 史生, 坂本 麻里, 栗本 拓治, 中西 裕子, 中村 誠
    神経眼科, Oct. 2022, Japanese, 日本神経眼科学会

  • Pros & Cons 2022年の多発性硬化症診療を考える Pros「#1.多発性硬化症はB細胞介在性疾患である」
    千原 典夫
    神経免疫学, Oct. 2022, Japanese, (一社)日本神経免疫学会
    [Invited]

  • 自己免疫性脳炎の疾患活動期では末梢血でplasmablastsが増加する
    原 敦, 千原 典夫, 赤谷 律, 辻 麻人, 刀坂 公崇, 錦織 隆成, 近藤 誉之, 塩見 悠真, 橋本 黎, 吉村 元, 川本 未知
    臨床神経学, Oct. 2022, Japanese, (一社)日本神経学会

  • てんかん診療における長時間ビデオ脳波モニタリングの病棟運用開始後の安全性検証
    植松 美和, 武田 早紀, 中西 のりこ, 堺 亜香, 中谷 真子, 廣田 大, 十河 正弥, 岡山 公宣, 千原 典夫, 松本 理器
    臨床神経学, Oct. 2022, Japanese, (一社)日本神経学会

  • てんかん外科における覚醒下手術での言語機能マッピングの有用性
    的場 健人, 藤本 陽介, 十河 正弥, 甲田 一馬, 森本 耕平, 岡山 公宣, 千原 典夫, 松本 理器, 篠山 隆司
    臨床神経学, Oct. 2022, Japanese, (一社)日本神経学会

  • 転写因子c-Mafは多発性硬化症におけるCD8+T細胞のPD-1発現を促進し,免疫制御機能を発揮する
    古東 秀介, 千原 典夫, 赤谷 律, 原 敦, 関口 兼司, 松本 理器, 戸田 達史
    神経免疫学, Oct. 2022, Japanese, (一社)日本神経免疫学会

  • NMO2 視神経脊髄炎に対するミコフェノール酸モフェチルによる再発抑制と安全性評価のためのオープン試験
    赤谷 律, 千原 典夫, 古東 秀介, 大森 崇, 関口 兼司, 松本 理器
    神経免疫学, Oct. 2022, Japanese, (一社)日本神経免疫学会

  • 脳炎・脳症 自己免疫性脳炎の疾患活動期では末梢血でplasmablastsが上昇しTfhのサブセットが変化する
    原 敦, 千原 典夫, 赤谷 律, 辻 麻人, 刀坂 公崇, 錦織 隆成, 近藤 誉之, 大塚 喜久, 影山 恭史, 吉村 元, 川本 未知, 松本 理器
    神経免疫学, Oct. 2022, Japanese, (一社)日本神経免疫学会

  • エクリズマブ導入により寛解後ステロイド減量に伴い再増悪をきたした難治性重症筋無力症の1例
    芦崎 太一朗, 千原 典夫, 牧野 愛, 西居 正汰, 十河 正弥, 上田 健博, 関口 兼司, 松本 理器
    神経治療学, Oct. 2022, Japanese, (一社)日本神経治療学会

  • 免疫チェックポイント阻害薬による治療中に生じたギラン・バレー症候群様の多発神経炎の1例
    大塚 晴彦, 高橋 甲介, 松本 由佳理, 織田 好子, 小野 竜輔, 上月 惇, 土田 愛, 武田 涼輔, 千原 典夫, 久保 亮治
    日本皮膚科学会雑誌, May 2022, Japanese, (公社)日本皮膚科学会

  • 視神経脊髄炎に対するミコフェノール酸モフェチルによる再発抑制と安全性の評価
    赤谷律, 千原典夫, 古東秀介, 立花久嗣, 大塚喜久, 上田健博, 大森崇, 関口兼司, 松本理器
    日本神経学会学術大会プログラム・抄録集, 2022

  • Electrographic seizures in NCSE can be associated with better outcomes; a two-center retrospective study
    甲田一馬, 十河正弥, 岡山公宣, 岡山公宣, 千原典夫, 上田健博, 上田健博, 関口兼司, 影山恭史, 松本理器
    てんかん研究, 2022

  • 院内限定オンライン会議・ワイヤレス音声ガイダンスを用いた入院患者カンファレンス
    関口兼司, 千原典夫, 十河正弥, 岡山公宣, 上田健博, 松本理器
    日本神経学会学術大会プログラム・抄録集, 2022

  • 一過性の脳炎様症状後に、拡散強調画像における高信号域の拡大が確認された神経核内封入体病の一例
    赤澤 明香, 辻 麻人, 上田 健博, 十河 正弥, 関谷 博顕, 千原 典夫, 関口 兼司, 永田 倫之, 松本 理器
    臨床神経学, Jan. 2022, Japanese, (一社)日本神経学会

  • 円蓋部に限局するくも膜下出血で発症した脳静脈血栓症の3症例
    上月惇, 十河正弥, 岡山公宣, 千原典夫, 上田健博, 関口兼司, 藤本陽介, 長嶋宏明, 篠山隆司, 松本理器
    日本内科学会雑誌, 2022

  • 5年の経過で再発・寛解を繰り返しCLIPPERSが先行してT細胞リンパ腫と診断した一例
    荒木 健, 末廣 大知, 立花 久嗣, 田中 伴典, 坂井 里奈, 水谷 優, 齊藤 泰之, 藥師神 公和, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Dec. 2021, Japanese, (一社)日本神経学会

  • 全身性エリテマトーデス、シェーグレン症候群の関与が疑われた運動神経優位の自己免疫性多発神経炎の1例
    末廣 大知, 赤澤 明香, 岡山 公宣, 関谷 博顕, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    神経治療学, Oct. 2021, Japanese, (一社)日本神経治療学会

  • 全身性エリテマトーデス、シェーグレン症候群の関与が疑われた運動神経優位の自己免疫性多発神経炎の1例
    末廣 大知, 赤澤 明香, 岡山 公宣, 関谷 博顕, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    神経治療学, Oct. 2021, Japanese, (一社)日本神経治療学会

  • 超高齢発症重症筋無力症(Ultra-late-onset MG)の臨床的特徴について
    辻 麻人, 千原 典夫, 十河 正弥, 岡山 公宣, 上田 健博, 関口 兼司, 松本 理器
    神経免疫学, Oct. 2021, Japanese, (一社)日本神経免疫学会

  • 自己免疫性脳炎の疾患活動期では末梢血でplasmablastsが増加する
    原 敦, 千原 典夫, 赤谷 律, 辻 麻人, 刀坂 公崇, 錦織 隆成, 近藤 誉之, 塩見 悠真, 橋本 黎, 吉村 元, 川本 未知, 松本 理器
    神経免疫学, Oct. 2021, Japanese, (一社)日本神経免疫学会

  • 抗MOG抗体関連疾患における画像上のくすぶり病変の意義
    刀坂 公崇, 千原 典夫, 栗本 拓治, 十河 正弥, 上田 健博, 関口 兼司, 中村 誠, 松本 理器
    神経免疫学, Oct. 2021, Japanese, (一社)日本神経免疫学会

  • 抗AQP4抗体陽性NMOSD患者末梢血ではB細胞中のDN2の割合が増大し、病勢を反映している
    赤谷 律, 千原 典夫, 原 敦, 古東 秀介, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • てんかん診療における長時間ビデオ脳波検査の病棟運用開始に向けた多職種での取り組み
    齋藤 早紀, 中谷 真子, 高谷 直美, 渡辺 優子, 堺 亜香, 植松 美和, 十河 正弥, 千原 典夫, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • 球麻痺で発症し診断に時間を要した高齢発症ALSの1例
    村上 友梨, 関谷 博顕, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • クリプトコッカス髄膜脳炎後にてんかん性失語重積状態をきたし治療に難渋した一例
    北野 良多, 十河 正弥, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • 胸腺腫非合併重症筋無力症患者に対する胸腺摘除術の有無が予後に与える影響の検討
    一柳 明希子, 上田 健博, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • 抗MOG抗体関連疾患におけるくすぶり病変は疾患活動性を反映する
    刀坂 公崇, 千原 典夫, 栗本 拓治, 十河 正弥, 関谷 博顕, 上田 健博, 関口 兼司, 中村 誠, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • 超高齢発症(Ultra-late-onset)重症筋無力症は集学的治療を要する独立した疾患群である
    辻 麻人, 千原 典夫, 十河 正弥, 関谷 博顕, 上田 健博, 関口 兼司, 松本 理器
    臨床神経学, Sep. 2021, Japanese, (一社)日本神経学会

  • 一側性周期性放電に伴いepileptic negative myoclonusを呈した一例
    的場 健人, 十河 正弥, 森本 耕平, 岡山 公宣, 武田 侑己, 城間 京香, 末廣 大知, 千原 典夫, 松本 理器
    てんかん研究, Jul. 2021, Japanese, (一社)日本てんかん学会

  • 扁桃体腫大を伴う側頭葉てんかん(TLE-AE)におけるてんかん性放電の振幅最大点の検討
    赤澤 明香, 十河 正弥, 森本 耕平, 的場 健人, 岡山 公宣, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器
    てんかん研究, Jul. 2021, Japanese, (一社)日本てんかん学会

  • 自己免疫性てんかんの疾患活動期では抗体産生性plasmablastsが増加する
    原 敦, 千原 典夫, 赤谷 律, 錦織 隆成, 近藤 誉之, 松本 理器
    てんかん研究, Jul. 2021, Japanese, (一社)日本てんかん学会

  • IL-6 and its targeting therapy in autoimmune diseases in the CNS, including neuromyelitis optica and multiple sclerosis
    Norio Chihara
    Federation of Clinical Immunology Societies (FOCiS) 2021, Jun. 2021
    [Invited]

  • 緩徐進行性の意識障害と振戦・ミオクローヌスを呈した自己免疫性glial fibrillary acidic protein(GFAP)アストロサイトパチー症例の神経生理学的検討
    武田涼輔, 岡山公宣, 土田愛, 上月淳, 曽菲亜, 十河正弥, 千原典夫, 上田健博, 関口兼司, 松本理器
    臨床神経生理学(Web), 2021

  • 地域基幹病院神経内科における外来てんかん診療の実際
    清家 尚彦, 千原 典夫, 松下 達生
    臨床神経学, Nov. 2020, Japanese, (一社)日本神経学会

  • 当院におけるTrousseau症候群に伴う脳梗塞患者14例の臨床像の検討
    末廣 大知, 上田 健博, 立花 久嗣, 荒木 健, 的場 健人, 辻 佑木生, 大塚 喜久, 千原 典夫, 関口 兼司, 松本 理器
    臨床神経学, Nov. 2020, Japanese, (一社)日本神経学会

  • 多発性硬化症における変形性脊椎症は脊髄病変と関連する
    古東 秀介, 千原 典夫, 小田 哲也, 中野 孝宏, 下村 雅浩, 細見 雅史, 松本 理器, 濱口 浩敏
    臨床神経学, Nov. 2020, Japanese, (一社)日本神経学会

  • B細胞の表現型解析は抗AQP4抗体陽性視神経脊髄炎関連疾患と他疾患の鑑別に有用である
    赤谷 律, 千原 典夫, 古東 秀介, 松本 理器
    臨床神経学, Nov. 2020, Japanese, (一社)日本神経学会

  • 免疫チェックポイント阻害薬誘発筋炎2症例の診断マーカーの検索
    原 敦, 関口 兼司, 山口 星一郎, 小牧 遼平, 末廣 大知, 森本 耕平, 野田 佳克, 千原 典夫, 松本 理器
    臨床神経学, Nov. 2020, Japanese, (一社)日本神経学会

  • 異なる治療反応性を示した免疫チェックポイント阻害薬誘発筋炎の2症例
    原 敦, 千原 典夫, 赤谷 律, 山口 星一郎, 小牧 遼平, 末廣 大知, 森本 耕平, 野田 佳克, 関口 兼司, 松本 理器
    神経免疫学, Oct. 2020, Japanese, 日本神経免疫学会

  • 経過中にキャッスルマン病と診断した多クローン性高γグロブリン血症を伴う多巣性運動ニューロパチーの1例
    城間 京香, 千原 典夫, 原 敦, 水谷 優, 関口 兼司, 松本 利器
    神経免疫学, Oct. 2020, Japanese, 日本神経免疫学会

  • 視神経脊髄炎と類縁疾患の鑑別にB細胞の表現型解析が有用である
    赤谷 律, 千原 典夫, 原 敦, 古東 秀介, 松本 理器
    神経免疫学, Oct. 2020, Japanese, 日本神経免疫学会

  • 多発性硬化症における脊髄病変と変形性脊椎症の関連についての検討
    古東 秀介, 千原 典夫, 小田 哲也, 上月 惇, 山口 星一郎, 武田 涼輔, 下村 雅浩, 細見 雅史, 松本 理器, 濱口 浩敏
    神経免疫学, Oct. 2020, Japanese, 日本神経免疫学会

  • ヘルパーT細胞の共抑制分子発現はMSとNMOの多様性を反映している
    千原 典夫, 赤谷 律, 古東 秀介, 原 敦, 松本 理器
    神経免疫学, Oct. 2020, Japanese, 日本神経免疫学会

  • 自己免疫性てんかんの免疫動態の探索
    千原典夫, 赤谷律, 錦織隆成, 松本理器
    精神・神経疾患研究開発費「難治性神経疾患における免疫病態の解明と診断・治療法開発」班, Dec. 2019, Japanese
    [Invited]

  • 神経系疾患について-筋萎縮性側索硬化症 脊髄小脳変性症 重症筋無力症 多発性硬化症を中心に
    千原 典夫
    神戸市難病連医療講演・相談会, Dec. 2019
    [Invited]
    Public discourse

  • 緩徐進行性の小脳性運動失調と魚鱗癬を呈したTrichothiodystrophyの一例
    渡部 俊介, 荒木 健, 辻 佑木生, 立花 久嗣, 千原 典夫, 上田 健博, 関口 兼司, 松本 理器, 中沢 由華
    臨床神経学, Dec. 2019, Japanese, (一社)日本神経学会

  • 当院で診療した重症筋無力症の臨床像および治療成績
    的場 健人, 千原 典夫, 大塚 喜久, 立花 久嗣, 上田 健博, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 筋萎縮性側索硬化症患者の診断遅延に繋がる因子の検討
    橋本 由貴, 野田 佳克, 上田 健博, 千原 典夫, 大塚 喜久, 立花 久嗣, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • SCA17の境界域リピート伸長症例の臨床的多様性
    高田 真利子, 佐竹 渉, 立花 久嗣, 上田 健博, 上田 直子, 大塚 喜久, 横田 一郎, 千原 典夫, 小別所 博, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 色素性乾皮症は中高年発症の小脳変性症の原因となる
    徳岡 秀紀, 佐竹 渉, 上田 健博, 辻本 昌理子, 千原 典夫, 関谷 博顕, 野田 佳克, 立花 久嗣, 大塚 喜久, 関口 兼司, 古和 久朋, 錦織 千佳子, 苅田 典生, 戸田 達史
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • NMOに対するMMFによる再発抑制と安全性確認のためのオープン試験
    千原 典夫, 古東 秀介, 赤谷 律, 立花 久嗣, 大塚 喜久, 上田 健博, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 超音波透過型高密度表面筋電図電極を用いたALSにおける線維束性収縮の検出
    関口 兼司, 渡部 俊介, 野田 佳克, 立花 久嗣, 大塚 喜久, 千原 典夫, 上田 健博
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 多発性硬化症の病態評価における光干渉断層計(OCT)の意義についての検討
    赤谷 律, 千原 典夫, 古東 秀介, 盛 崇太朗, 栗本 拓治, 立花 久嗣, 大塚 喜久, 上田 健博, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 多発性硬化症の急性期治療反応性と相関する脳脊髄液中のPD-1陽性CD8+ T細胞の役割
    古東 秀介, 千原 典夫, 赤谷 律, 関口 兼司, 戸田 達史
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 当院における脊髄性筋萎縮症成人例に対するヌシネルセン使用経験
    大塚 喜久, 橋本 黎, 荒木 健, 中野 孝宏, 的場 健人, 渡部 俊介, 辻 佑木生, 立花 久嗣, 千原 典夫, 上田 健博, 永井 正志, 粟野 宏之, 小幡 典彦, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • 当院で診断した多系統萎縮症の予後に関する検討
    上田 健博, 立花 久嗣, 大塚 喜久, 千原 典夫, 佐竹 渉, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • メモリー外来を受診した臨床経過の異なる脳アミロイドアンギオパチー関連微小出血3例
    立花 久嗣, 古和 久朋, 松山 賢一, 大塚 喜久, 千原 典夫, 上田 健博, 関口 兼司
    臨床神経学, Nov. 2019, Japanese, (一社)日本神経学会

  • Plasmablasts and neuroimmunological disorders.
    Chihara N
    Asia-Pacific School of Neuroimmunology (APSNI) of the International Society of Neuroimmunology, Seoul, Oct. 2019, English
    [Invited]
    Public discourse

  • 皮膚血管炎を合併したSjoegren症候群の1例
    辰岡 沙織, 橋本 真哉, 西山 智司, 永井 宏, 錦織 千佳子, 千原 典夫, 谷口 幸司
    皮膚の科学, Oct. 2019, Japanese, 日本皮膚科学会-大阪地方会・京滋地方会

  • 尖足により歩行困難を呈した抗neurofascin 155抗体陽性CIDPの一例
    森本 耕平, 関口 兼司, 渡部 俊介, 野田 佳克, 千原 典夫, 松本 理器
    臨床神経生理学, Oct. 2019, Japanese, (一社)日本臨床神経生理学会

  • 抗GAD抗体、抗LGI1抗体、抗GABAAR抗体陽性脳炎に対し、免疫治療が奏効した1例
    中野 孝宏, 的場 健人, 立花 久嗣, 大塚 喜久, 千原 典夫, 上田 健博, 関口 兼司, 濱口 浩敏, 古和 久朋, 松本 理器
    神経治療学, Oct. 2019, Japanese, (一社)日本神経治療学会

  • 多発性硬化症のあらまし
    千原 典夫
    2019年度 にしのみやなんれん 難病医療相談会, Sep. 2019
    [Invited]
    Public discourse

  • Induction and transcriptional regulation of the co-inhibitory gene module in T cells
    Chihara N
    Kobe Univeristy-University of Washington Joint Symposium on Molecular Pharmacology, Seattle, Sep. 2019, English
    [Invited]

  • 異常行動とけいれん発作で発症し、3種の抗神経抗体が陽性であった自己免疫性脳炎の1例
    的場 健人, 中野 孝宏, 立花 久嗣, 大塚 喜久, 千原 典夫, 上田 健博, 関口 兼司, 古和 久朋, 松本 理器
    てんかん研究, Sep. 2019, Japanese, (一社)日本てんかん学会

  • 多発性硬化症における制御性CD8+T細胞に関する検討
    古東 秀介, 千原 典夫, 赤谷 律, 関口 兼司, 松本 理器, 戸田 達史
    神経免疫学, Sep. 2019, Japanese, 日本神経免疫学会

  • 再発性視神経炎に対する免疫抑制剤の治療効果
    盛 崇太朗, 栗本 拓治, 村井 佑輔, 上田 香織, 坂本 麻里, 千原 典夫, 中西 裕子[山田], 中村 誠
    神経眼科, Aug. 2019, Japanese, 日本神経眼科学会

  • 両側性の faciobrachial dystonic seizure を呈した抗 LGI1 抗体陽性辺縁系脳炎の 1 例
    山口 星一郎, 末廣 大知, 森本 耕平, 千原 典夫, 辻 佑木生, 立花 久嗣, 上田 健博, 関口 兼司, 松本 理器
    第15回日本てんかん学会近畿地方会, Jul. 2019
    Oral presentation

  • 抗GAD抗体・抗LGI1抗体陽性脳炎に対し免疫治療を行い奏功した1例
    中野 孝宏, 的場 健人, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SEKIGUCHI KENJI, KOWA HISATOMO, MATSUMOTO RIKI
    第113回神経学会近畿地方会, Mar. 2019, Japanese, 日本神経学会近畿地方会, 大阪, Domestic conference
    Oral presentation

  • PD-1阻害薬投与後に急性脱髄性ポリニューロパチーを来たした1例
    橋本 黎, 辻 佑木生, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SATAKE WATARU, SEKIGUCHI KENJI, MATSUMOTO RIKI
    兵庫神経免疫研究会, Mar. 2019, Japanese, 日本製薬, 神戸市, Domestic conference
    Oral presentation

  • Perivenous inflammatory demyelination is the prominent pathology in myelin oligodendrocyte glycoprotein antibody-associated disease
    Yoshiki Takai, Misu Tatsuro, Kaneko Kimihiko, Norio Chihara, Kouidhi Narikawa, Satoko Tsuchida, Hiroya Nishida, Takahashi Toshiyuki, Masashi Aoki, Fujihara Kazuo
    BRAIN PATHOLOGY, Feb. 2019, English, WILEY

  • 尖足により歩行困難を呈した抗neurofascin155抗体陽性CIDPの一例
    森本耕平, 関口兼司, 渡部俊介, 野田佳克, 千原典夫, 松本理器
    臨床神経生理学(Web), 2019

  • 抗PD-1阻害薬ペムブロリズマブ投与後に横隔膜を主体とした筋炎を発症し、呼吸不全を呈した１例
    橋本 黎, 的場 健人, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SATAKE WATARU, SEKIGUCHI KENJI, MATSUMOTO RIKI, 白石 祐介, 井上 隆朗
    第112回神経学会近畿地方会, Dec. 2018, Japanese, 日本神経学会近畿地方会, 大阪, Domestic conference
    Oral presentation

  • 疾患修飾薬変更後に再発を繰り返し，抗ナタリズマブ抗体が陽性となった多発性硬化症の1例
    赤谷 律, CHIHARA NORIO, 刀坂 公崇, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, UEDA TAKEHIRO, SEKIGUCHI KENJI, KOWA HISATOMO, TODA TATSUSHI
    第36回日本神経治療学会学術集会, Nov. 2018, Japanese, 日本神経治療学会, 東京, Domestic conference
    Oral presentation

  • 児童期に前頭葉てんかんと診断され、成人後も嘔気を伴う発作を繰り返す一例
    橋本 黎, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SATAKE WATARU, SEKIGUCHI KENJI
    神戸てんかんカンファレンス（研究会）, Nov. 2018, Japanese, 大鵬製薬, 神戸市, Domestic conference
    Oral presentation

  • 多発性硬化症/視神経脊髄炎における調節不全T細胞の役割について
    CHIHARA NORIO, 古東 秀介, 赤谷 律, SEKIGUCHI KENJI
    第46回日本臨床免疫学会総会, Oct. 2018, Japanese, 日本臨床免疫学会, 長野(軽井沢), Domestic conference
    Poster presentation

  • 多発性硬化症におけるPD-1陽性CD8+ T細胞の脳脊髄液および末梢血での比較
    古東 秀介, CHIHARA NORIO, 赤谷 律, SEKIGUCHI KENJI, TODA TATSUSHI
    第30回日本神経免疫学会学術集会, Sep. 2018, Japanese, 日本神経免疫学会, 福島, Domestic conference
    Poster presentation

  • 腫瘍随伴性NMOSDにおけるPD-1/PD-L1経路の役割
    CHIHARA NORIO, 首藤 篤史, 古東 秀介, 赤谷 律, SEKIGUCHI KENJI, TODA TATSUSHI
    第30回日本神経免疫学会学術集会, Sep. 2018, Japanese, 日本神経免疫学会, 福島, Domestic conference
    Poster presentation

  • 抗ナタリズマブ抗体が陽性となった多発性硬化症の1例
    赤谷 律, CHIHARA NORIO, 刀坂 公崇, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, UEDA TAKEHIRO, SEKIGUCHI KENJI, KOWA HISATOMO, TODA TATSUSHI
    第30回日本神経免疫学会学術集会, Sep. 2018, Japanese, 日本神経免疫学会, 福島, Domestic conference
    Poster presentation

  • 肝硬変を背景に発症しメフロキンが有効であった進行性多巣性白質脳症（PML）の一例
    中野 孝宏, OHTSUKA YOSHIHISA, 横尾 紫穂, 渡部 俊介, CHIHARA NORIO, TACHIBANA HISATSUGU, UEDA TAKEHIRO, SEKIGUCHI KENJI
    第221回内科学会近畿地方会, Sep. 2018, Japanese, 日本内科学会近畿支部, 大阪, Domestic conference
    Oral presentation

  • ふらつきを主訴に来院し、小脳失調と眼位異常を認めた63歳男性例
    的場 健人, 徳岡 秀紀, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SATAKE WATARU, SEKIGUCHI KENJI
    第76回兵庫神経内科研究会, Sep. 2018, Japanese, 兵庫神経内科研究会, 兵庫, Domestic conference
    [Invited]
    Invited oral presentation

  • Paraneoplastic NMOSD preceding immune-escape of EG junction adenocarcinoma
    Norio Chihara, Atsushi Sudo, Shusuke Koto, Ritsu Akatani, Kenji Sekiguchi, Tatsushi Toda
    14th International Congress of Neuroimmunology, Aug. 2018, English, Brisbane, International conference
    Poster presentation

  • 反復刺激試験で神経筋接合部異常が示唆されたPhosphoglucomutase 1欠損症の一例
    武中 優, 関谷 博顕, TACHIBANA HISATSUGU, CHIHARA NORIO, UEDA TAKEHIRO, SEKIGUCHI KENJI, 西野 一三, 大野 欽司, 杉江 秀夫, TODA TATSUSHI
    第111回神経学会近畿地方会, Jul. 2018, Japanese, 日本神経学会近畿地方会, 大阪, Domestic conference
    Oral presentation

  • 反復する⼀過性の意識変容と異常⾏動を呈し，8ヶ⽉後の発作時脳波でNCSEと確定した82歳⼥性例
    岡山 公宣, 徳岡 秀紀, CHIHARA NORIO, SEKIGUCHI KENJI
    第14回日本てんかん学会近畿地方会, Jul. 2018, Japanese, 日本てんかん学会近畿地方会, 大阪, Domestic conference
    Oral presentation

  • 神経系疾患について-筋萎縮性側索硬化症 脊髄小脳変性症 多発性硬化症 後縦靭帯骨化症を中心に
    CHIHARA NORIO
    神戸市難病連主催第69回医療相談会, Jul. 2018, Japanese, 神戸市難病連, 兵庫, Domestic conference
    [Invited]
    Public discourse

  • 次々世代シークエンサーMinIONは髄膜脳炎の起因菌を迅速・包括的・高検出力で同定できる 1st choiceとしての医療実装へむけて
    SATAKE WATARU, 渡部 俊介, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, 河原 佳奈, KURIMOTO TAKUJI, 平社 亜沙子, NISHIO MARI, SEKIGUCHI KENJI, KANDA FUMIO, TODA TATSUSHI, Runtuwene L.R, 鈴木 穣
    第66回日本化学療法学会総会, Jun. 2018, Japanese, 日本化学療法学会, 岡山市, Domestic conference
    Oral presentation

  • 日本語版Guy’s Neurological Disability Scaleを用いた多発性硬化症の臨床的評価
    赤谷 律, CHIHARA NORIO, 渡部 俊介, TACHIBANA HISATSUGU, 古東 秀介, OHTSUKA YOSHIHISA, UEDA TAKEHIRO, SEKIGUCHI KENJI, KOWA HISATOMO, TODA TATSUSHI
    第59回日本神経学会学術大会, May 2018, Japanese, 日本神経学会, 北海道, Domestic conference
    Poster presentation

  • 当院で実施した常染色体優性遺伝性脊髄小脳変性症に対する遺伝学的検査の検討
    UEDA TAKEHIRO, SATAKE WATARU, TACHIBANA HISATSUGU, OHTSUKA YOSHIHISA, CHIHARA NORIO, SEKIGUCHI KENJI, KOWA HISATOMO, 苅田 典生, TODA TATSUSHI
    第59回日本神経学会学術大会, May 2018, Japanese, 日本神経学会, 札幌, Domestic conference
    Poster presentation

  • 多系統萎縮症の十字サインにおけるDouble Inversion Recovery法の有用性の検討
    OHTSUKA YOSHIHISA, UEDA TAKEHIRO, CHIHARA NORIO, 徳岡 秀紀, TACHIBANA HISATSUGU, SATAKE WATARU, SEKIGUCHI KENJI
    第５９回日本神経学会学術大会, May 2018, Japanese, 日本神経学会, 札幌, Domestic conference
    Poster presentation

  • 筋萎縮性側索硬化症患者の初発症状の出現部位と受療行動に関する検討
    橋本 由貴, SEKIGUCHI KENJI, 野田 佳克, UEDA TAKEHIRO, CHIHARA NORIO, OHTSUKA YOSHIHISA, TACHIBANA HISATSUGU, KANDA FUMIO
    第59回日本神経学会学術総会, May 2018, Japanese, 日本神経学会, 札幌市, Domestic conference
    Poster presentation

  • アルツハイマー型認知症と健忘型経度認知障害にみられる気分障害と大脳白質病変の検討
    TACHIBANA HISATSUGU, 鷲田 和夫, OHTSUKA YOSHIHISA, CHIHARA NORIO, UEDA TAKEHIRO, SATAKE WATARU, TODA TATSUSHI
    第59回日本神経学会学術大会, May 2018, Japanese, 日本神経学会, 札幌, Domestic conference
    Poster presentation

  • The role of PD-0 expressing T cells in the cerebrospinal fluid of MS and NMO
    CHIHARA NORIO, 古東 秀介, 赤谷 律, SEKIGUCHI KENJI, TODA TATSUSHI
    第59回日本神経学会学術大会, May 2018, English, 日本神経学会, 北海道, Domestic conference
    Poster presentation

  • PD-1陽性CD8+ T細胞は多発性硬化症の治療効果を反映する
    古東 秀介, CHIHARA NORIO, 赤谷 律, SEKIGUCHI KENJI, TODA TATSUSHI
    第59回日本神経学会学術大会, May 2018, Japanese, 日本神経学会, 北海道, Domestic conference
    Oral presentation

  • Motor cortex low intensities on SWI in progressive muscular atrophy with widespread fasciculations
    Kenji Sekiguchi, Yoshikatsu Noda, Syunsuke Watanabe, Syusuke Koto, Yuki Hashimoto, Hisatsugu Tachibana, Yoshihisa Otsuka, Norio Chihara, Takehiro Ueda
    第59回日本神経学会学術大会, May 2018, English, 日本神経学会, 札幌, Domestic conference
    Poster presentation

  • 次々世代シークエンサーMinIONは髄膜脳炎の起因菌を迅速・包括的・高検出力で同定できる 1st choiceとしての医療実装へむけて
    佐竹 渉, 渡部 俊介, 立花 久嗣, 大塚 喜久, 千原 典夫, 上田 健博, 河原 佳奈, 栗本 拓治, 平社 亜沙子, 西尾 真理, 関口 兼司, 苅田 典生, 戸田 達史, Runtuwene L.R., 鈴木 穣
    日本化学療法学会雑誌, Apr. 2018, Japanese, (公社)日本化学療法学会

  • Two cases of intravascular lymphoma developed with cerebral infarction and diagnosed by skin biopsy
    Otsuka Yoshihisa, 下村雅浩, 西居正汰, 渡部俊介, Tachibana Hisatsugu, Chihara Norio, Ueda Takehiro, Sekiguchi Kenji
    第43回日本脳卒中学会学術集会, Mar. 2018, Japanese, The Japan Stroke Society, 福岡, Domestic conference
    Poster presentation

  • 緩徐に進行し，遺伝性との鑑別を要した 孤発性クロイツフェルト・ヤコブ病の1例
    刀坂 公崇, 赤谷 律, Otsuka Yoshihisa, 髙田 真利子, Chihara Norio, Ueda Takehiro, Sekiguchi Kenji
    第110回近畿地方会, Mar. 2018, Japanese, 日本神経学会, 京都, Domestic conference
    Oral presentation

  • 腫瘍随伴性NMOSDにおけるPD-1/PD-L1の経路の役割
    千原典夫, 首藤篤史, 古東秀介, 赤谷律, 関口兼司, 戸田達史
    Neuroimmunology, 2018

  • 神経系疾患について-筋萎縮性側索硬化症 脊髄小脳変性症 重症筋無力症 後縦靭帯骨化症 多発性硬化症を中心に
    千原 典夫
    神戸市難病連主催第68回医療相談会, Dec. 2017
    [Invited]
    Public discourse

  • 両側視神経障害と中脳病変を呈した中枢神経アスペルギルス症の一例
    渡部俊介, Tachibana Hisatsugu, Otsuka Yoshihisa, Chihara Norio, Ueda Takehiro, 河原佳奈, Kurimoto Takuji, 平社亜沙子, Nishio Mari, Sekiguchi Kenji, 苅田典生, Toda Tatsushi
    日本神経学会第109回近畿地方会, Dec. 2017, Japanese, Japanese Society of Neurology, 大阪, Domestic conference
    Oral presentation

  • Guy's Neurological Disability Scaleを用いた多発性硬化症の非身体障害機能評価(会議録)
    赤谷律, 千原典夫, 立花久嗣, 古東秀介, 大塚喜久, 上田健博, Sekiguchi Kenji, 古和久朋, 戸田達史
    神経免疫学, Oct. 2017, Japanese

  • MS・NMO1 PD-1陽性CD8 T細胞は多発性硬化症の治療効果を反映するバイオマーカーになる
    古東秀介, 千原典夫, Sekiguchi Kenji, 戸田達史
    神経免疫学, Oct. 2017, Japanese

  • Guy's Neurological Disability Scaleを用いた多発性硬化症の非身体障害機能評価
    赤谷 律, 千原 典夫, 立花 久嗣, 古東 秀介, 大塚 喜久, 上田 健博, 関口 兼司, 古和 久朋, 戸田 達史
    神経免疫学, Oct. 2017, Japanese, 日本神経免疫学会

  • MS・NMO1 PD-1陽性CD8+T細胞は多発性硬化症の治療効果を反映するバイオマーカーになる
    古東 秀介, 千原 典夫, 関口 兼司, 戸田 達史
    神経免疫学, Oct. 2017, Japanese, 日本神経免疫学会

  • 造影効果を伴わない延髄病変で発症し炎症性脱髄性疾患と鑑別を要した膠芽腫の一例
    下村 雅浩, 関口 兼司, 立花 久嗣, 千原 典夫, 上田 健博, 古和 久朋, 小牧 遼平, 濱口 浩敏, 苅田 典生, 戸田 達史
    臨床神経学, Oct. 2017, Japanese, (一社)日本神経学会

  • PD-1陽性CD8+T細胞は多発性硬化症の治療効果を反映するバイオマーカーになる
    古東秀介, Chihara Norio, Sekiguchi Kenji, Toda Tatsushi
    第29回日本神経免疫学会, Oct. 2017, Japanese, 日本神経免疫学会, 札幌, Domestic conference
    Oral presentation

  • Guy’s Neurological Disability Scaleを用いた多発性硬化症の非身体障害機能評価
    赤谷 律, Chihara Norio, Tachibana Hisatsugu, 古東 秀介, Otsuka Yoshihisa, Ueda Takehiro, Sekiguchi Kenji, Kowa Hisatomo, Toda Tatsushi
    第29回神経免疫学会学術集会, Oct. 2017, Japanese, 日本神経免疫学会, 札幌, Domestic conference
    Poster presentation

  • A gene module driving co-inhibitory receptors expression on T cells
    Chihara Norio, Asaf Madi, Ana C. Anderson, Aviv Regev, Vijay K. Kuchroo
    XXIII World Congress of Neurology (WCN2017), Sep. 2017, English, World Federation of Neurology, Kyoto, Japan, International conference
    Poster presentation

  • 造影効果を伴わない延髄病変で発症し炎症性脱髄疾患と鑑別を要した膠芽腫の一例
    下村雅浩, Sekiguchi Kenji, Tachibana Hisatsugu, Chihara Norio, Ueda Takehiro, Kowa Hisatomo, 小牧遼平, 濵口浩敏, 苅田典生, Toda Tatsushi
    第108回日本神経学会近畿地方会, Jul. 2017, Japanese, 日本神経学会, 大阪, Domestic conference
    Oral presentation

  • 磁化率強調画像で多発する低信号を呈した血管内大細胞型B細胞性リンパ腫の一例
    下村 雅浩, 立花 久嗣, 梶本 裕人, 千原 典夫, 上田 健博, 関口 兼司, 古和 久朋, 苅田 典生, 永井 宏, 錦織 千佳子, 原 重雄, 戸田 達史
    臨床神経学, Jun. 2017, Japanese, (一社)日本神経学会

  • 抗AMPAR抗体、抗CV2/CRMP5抗体、抗GABAA R抗体が陽性であったStiff-person症候群の一例
    首藤 篤史, 立花 久嗣, 高田 真利子, 千原 典夫, 上田 健博, 関口 兼司, 古和 久朋, 飯塚 高浩, 苅田 典生, 戸田 達史
    臨床神経学, Mar. 2017, Japanese, (一社)日本神経学会

  • てんかん発作で発症したMOG antibody associated encephalomyelitisの一例
    武中 優, 千原 典夫, 神保 直江, 金子 仁彦, 立花 久嗣, 上田 健博, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Mar. 2017, Japanese, (一社)日本神経学会

  • 磁化率強調画像で多発する低信号を呈した血管内大細胞型B細胞性リンパ腫の一例
    下村 雅浩, Tachibana Hisatsugu, 梶本 裕人, Chihara Norio, Ueda Takehiro, Sekiguchi Kenji, Kowa Hisatomo, Kanda Fumio, Nagai Hiroshi, Nishigori Chikako, Hara Shigeo, Toda Tatsushi
    第107回日本神経学会近畿地方会, Mar. 2017, Japanese, 日本神経内科学会, 大阪, Domestic conference
    [Invited]
    Invited oral presentation

  • 抗AMPAR抗体,抗CV2/CRMP5抗体,抗GABAAR抗体が陽性であったStiff-person症候群の一例
    首藤篤史, 立花久嗣, 高田真利子, 千原典夫, 上田健博, 関口兼司, 古和久朋, 飯塚高浩, 苅田典生, 戸田達史
    臨床神経学(Web), 2017

  • 左視床病変で発症し免疫治療に抵抗性であった視神経脊髄炎スペクトラム疾患の一例
    武中 優, 千原 典夫, 穂積 かおり, 松岡 亮介, 北村 重和, 辻 佑木生, 立花 久嗣, 上田 健博, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Nov. 2016, Japanese, (一社)日本神経学会

  • 顔面肩甲上腕型筋ジストロフィー2型(FSHD2)と遺伝子診断した1例
    徳岡 秀紀, 上田 健博, 遠藤 浩信, 立花 久嗣, 千原 典夫, 関口 兼司, 古和 久朋, 苅田 典生, 濱中 耕平, 西野 一三, 戸田 達史
    臨床神経学, Nov. 2016, Japanese, (一社)日本神経学会

  • 抗AMPAR抗体, 抗CV2/CRMP5抗体, 抗GABAAR抗体が陽性であったStiff-person症候群の一例
    首藤 篤史, Tachibana Hisatsugu, 髙田 真利子, Chihara Norio, Ueda Takehiro, Sekiguchi Kenji, Kowa Hisatomo, 飯塚 高浩, Kanda Fumio, Toda Tatsushi
    第106回日本神経学会近畿地方会, Nov. 2016, Japanese, 日本神経学会近畿地方会, 京都, Domestic conference
    Oral presentation

  • てんかん発作で発症した MOG antibody associated encephalomyelitisの一例
    武中 優, Chihara Norio, Jimbo Naoe, 金子 仁彦, Tachibana Hisatsugu, Ueda Takehiro, Sekiguchi Kenji, Kowa Hisatomo, Kanda Fumio, Toda Tatsushi
    日本神経学会第106回近畿地方会, Nov. 2016, Japanese, 日本神経学会, 京都, Domestic conference
    Oral presentation

  • 葉酸、ビタミンB12補充療法が有効であった、亜急性連合性脊髄変性症様の病変を呈した1例
    辻 佑木生, 立花 久嗣, 千原 典夫, 上田 健博, 佐竹 渉, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    神経治療学, Oct. 2016, Japanese, (一社)日本神経治療学会

  • 抗AQP4抗体陽性視神経炎に対する血液浄化療法の治療効果
    盛 崇太朗, 栗本 拓治, 坂本 麻里, 上田 香織, 井上 結香子, 千原 典夫, 金森 章泰, 山田 裕子, 中村 誠
    神経眼科, Oct. 2016, Japanese, 日本神経眼科学会

  • Mechanisms driving co-inhibitory receptor expression on T cells
    Chihara Norio, Asaf Madi, Takaaki Kondo, Meromit Singer, Huiyuan Zhang, Chao Wang, Sema Kurtulus, Patrick Burkett, Aviv Regev, Ana C. Anderson, Vijay K. Kuchroo
    International Congress of Immunology, Aug. 2016, English, International Union of Immunological Societies, Melbourne, Australia, International conference
    Oral presentation

  • 左視床病変で発症し治療抵抗性であった視神経脊髄炎スペクトラム疾患の一例
    武中 優, Chihara Norio, 穂積 かおり, Tachibana Hisatsugu, Ueda Takehiro, Sekiguchi Kenji, Kowa Hisatomo, Kanda Fumio, Toda Tatsushi
    日本神経学会第105回近畿地方会, Jul. 2016, Japanese, 日本神経学会, 京都, Domestic conference
    Oral presentation

  • 抗CRMP5抗体を認めIsaacs症候群が疑われた一例
    首藤 篤史, Tachibana Hisatsugu, Ueda Takehiro, Chihara Norio, Sekiguchi Kenji, Kowa Hisatomo, Kanda Fumio, Toda Tatsushi
    第4回近畿免疫性神経疾患研究会, Jul. 2016, Japanese, 近畿免疫性神経疾患研究会, 大阪, Domestic conference
    Oral presentation

  • 顔面肩甲上腕型筋ジストロフィー2型(FSHD2)と遺伝子診断した1例
    徳岡 秀紀, Ueda Takehiro, 遠藤 浩信, Tachibana Hisatsugu, Chihara Norio, Sekiguchi Kenji, Kowa Hisatomo, Kanda Fumio, 濱中 耕平, 西野 一三, Toda Tatsushi
    第105回日本神経学会近畿地方会, Jul. 2016, Japanese, 日本神経学会, 京都, Domestic conference
    Oral presentation

  • 葉酸,ビタミンB12補充療法が有効であった,亜急性連合性脊髄変性症様の病変を呈した1例
    辻佑木生, 立花久嗣, 千原典夫, 上田健博, 佐竹渉, 関口兼司, 古和久朋, 苅田典生, 戸田達史
    神経治療学(Web), 2016

  • 慢性炎症性脱髄性多発神経炎におけるT細胞ケモカイン受容体
    池口 亮太郎, 佐藤 和貴郎, 千原 典夫, 荒浪 利昌, 岡本 智子, 村田 美穂, 清水 優子, 北川 一夫, 山村 隆
    末梢神経, Dec. 2015, Japanese, 日本末梢神経学会

  • 慢性炎症性脱髄性多発神経炎におけるヘルパーT細胞ケモカイン受容体に関する研究
    池口 亮太郎, 佐藤 和貴郎, 千原 典夫, 荒浪 利昌, 岡本 智子, 村田 美穂, 清水 優子, 北川 一夫, 山村 隆
    臨床神経学, Dec. 2015, Japanese, (一社)日本神経学会

  • 慢性炎症性脱髄性多発神経炎におけるT細胞ケモカイン受容体
    IKEGUCHI RYOTARO, IKEGUCHI RYOTARO, SATO WAKIO, CHIHARA NORIO, ARANAMI TOSHIMASA, OKAMOTO TOMOKO, MURATA MIHO, SHIMIZU YUKO, KITAGAWA KAZUO, YAMAMURA TAKASHI
    日本末梢神経学会学術集会プログラム・抄録, Jul. 2015, Japanese

  • 4型胃癌様の胃壁内転移をきたした食道扁平上皮癌の1例
    三島 圭介, 渡邊 昌則, 野村 聡, 塙 秀暁, 前島 顕太郎, 千原 直人, 坊 英樹, 鈴木 英之, 許田 典夫, 内田 英二
    日本食道学会学術集会プログラム・抄録集, Jul. 2015, Japanese, (NPO)日本食道学会

  • Fingolimod導入後早期に多数の再発病巣をみとめた多発性硬化症の1例
    遠藤 浩信, 千原 典夫, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Jun. 2015, Japanese, (一社)日本神経学会, 症例は46歳女性。14年前に多発性硬化症と診断し2001年からinterferon β-1bを開始したが精神症状で2006年に中断した。以後年に1〜2回再発しEDSSは2.5から6.5となった。2012年4月の再発時、methylprednisolone pulse療法後からfingolimod(FTY)投与した。導入20日後から構音障害と下肢脱力がみられ、脳MRIで側脳室周囲、皮質直下白質、小脳半球に数mm程の20ヶ所以上のGd造影効果をともなう病変をみとめた。再発頻度の多い症例へのFTY導入は慎重にし、早期はとくに注意して経過観察をする必要がある。(著者抄録)

  • Plasmablasts as AQP4-Ab producers in the patients of Neuromyelitis Optica．
    Chihara N,Aranami T, Oki S,Matsuoka T,Nakamura M, Okamoto T,Murata M,Toda T,Miyake S,Yamamura T
    2014 joint ACTRIMS-ECTRIMS meeting, Boston, Sep. 2014, English
    Poster presentation

  • Plasmablasts as AQP4-Ab producers in the pathogenesis of neuromyelitis optica
    N. Chihara, T. Aranami, S. Oki, T. Matsuoka, M. Nakamura, T. Okamoto, M. Murata, T. Toda, S. Miyake, T. Yamamura
    MULTIPLE SCLEROSIS JOURNAL, Sep. 2014, English, SAGE PUBLICATIONS LTD

  • 中枢神経系の自己免疫疾患におけるプラズマブラスト
    中村 雅一, 千原 典夫, 山村 隆
    日本臨床免疫学会会誌, Aug. 2014, Japanese, 日本臨床免疫学会

  • 髄液糖の低下を示した特発性肥厚性硬膜炎の一例
    遠藤 浩信, 上中 健, 千原 典夫, 鷲田 和夫, 安井 直子, 久我 敦, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Jan. 2014, Japanese, (一社)日本神経学会

  • パーキンソニズムを呈した22q11.2欠失症候群の1例
    赤谷 律, 福岡 秀規, 本岡 里英子, 千原 典夫, 佐竹 渉, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Jan. 2014, Japanese, (一社)日本神経学会

  • 抗ミトコンドリア抗体陽性筋炎におけるミトコンドリア機能障害についての検討
    上中 健, 古和 久朋, 赤谷 律, 遠藤 浩信, 井元 万紀子, 本岡 里英子, 立花 久嗣, 千原 典夫, 関 恒慶, 安井 直子, 久我 敦, 関口 兼司, 濱口 浩敏, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2013, Japanese, (一社)日本神経学会

  • Paced Auditory Serial Addition TestはFingolimod治療による早期効果の指標になる
    立花 久嗣, 千原 典夫, 遠藤 浩信, 上田 健博, 安井 直子, 久我 敦, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2013, Japanese, (一社)日本神経学会

  • フィンゴリモド導入における初期脱落例の検討
    遠藤 浩信, 千原 典夫, 赤谷 律, 井元 万紀子, 上中 健, 本岡 里英子, 立花 久嗣, 安井 直子, 鷲田 和夫, 久我 敦, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2013, Japanese, (一社)日本神経学会

  • ヒトパピローマウイルスワクチン接種に伴う急性散在性脳脊髄炎が疑われた2症例の検討
    関口 兼司, 赤谷 律, 遠藤 浩信, 井元 万紀子, 上中 健, 本岡 里英子, 立花 久嗣, 千原 典夫, 鷲田 和夫, 安井 直子, 久我 敦, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2013, Japanese, (一社)日本神経学会

  • Human Immunology 疾患理解から治療へ 多発性硬化症における脳脊髄液T細胞のケモカイン受容体解析
    佐藤 和貴郎, 荒浪 利昌, 冨田 敦子, 千原 典夫, 岡本 智子, 林 幼偉, 村田 美穂, 三宅 幸子, 山村 隆
    神経免疫学, Nov. 2013, Japanese, 日本神経免疫学会

  • Human Immunology 疾患理解から治療へ 多発性硬化症における脳脊髄液T細胞のケモカイン受容体解析
    佐藤 和貴郎, 荒浪 利昌, 冨田 敦子, 千原 典夫, 岡本 智子, 林 幼偉, 村田 美穂, 三宅 幸子, 山村 隆
    日本臨床免疫学会会誌, Oct. 2013, Japanese, 日本臨床免疫学会

  • フィンゴリモド導入直後に多数の再発病巣を認めた多発性硬化症(MS)の一例
    遠藤 浩信, 千原 典夫, 立花 久嗣, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Jul. 2013, Japanese, (一社)日本神経学会

  • 左顔面麻痺で発症し、脳幹部にTumefactive demyelinatig lesionを呈した68歳女性の一例
    本岡 里英子, 千原 典夫, 赤谷 律, 佐竹 渉, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Jul. 2013, Japanese, (一社)日本神経学会

  • 難治性ニューロパチーの診断技術と治療法の開発に関する研究 難治性神経疾患に対する個別化医療開発,免疫性ニューロパチーの治療
    山村隆, 千原典夫, 佐藤和貴郎, 冨田敦子, 林幼偉, 小川雅文, 岡本智子, 村田美穂, 三宅幸子, 荒浪利昌
    難治性ニューロパチーの診断技術と治療法の開発に関する研究 平成22-24年度 総括研究報告書, 2013

  • 合同シンポジウム2-3  多発性硬化症における脳脊髄液T細胞のケモカイン受容体解析
    佐藤 和貴郎, 荒浪 利昌, 冨田 敦子, 千原 典夫, 岡本 智子, 林 幼偉, 村田 美穂, 三宅 幸子, 山村 隆
    日本臨床免疫学会会誌, 2013, Japanese, The Japan Society for Clinical Immunology, 多発性硬化症（Multiple Sclerosis : MS）は炎症性脱髄を特徴とする，代表的な中枢神経を場とする臓器特異的自己免疫疾患である．再発と寛解そして進行性の経過が一般的である．根本原因は不明であるがリンパ球を標的とした治療が有効である．MSの病理ではIFNγ産生性のTh1細胞とともにIL-17産生性のTh17細胞の病原性が示唆されているが，詳細は不明である．
     Th1細胞とTh17細胞は，異なるケモカイン受容体を発現するため，逆にケモカイン受容体の発現パターンからTh1/Th17細胞の関与を推定しうる．MS患者のCD4+T細胞におけるCCR2，CCR4，CCR5，CCR6の発現の有無をフローサイトメトリーで調べ，計16種の細胞分画（例えばCCR2+CCR4-CCR5-CCR6+など）の頻度を得た．末梢血CD4+T細胞における各分画の頻度はコントロールと比べて有意な変化を認めなかったが，再発期MS患者の脳脊髄液のCD4+T細胞を調べると，CCR2+CCR5+細胞の頻度が，末梢血中の頻度と比べ疾患特異的に増加していた．すなわち同細胞が中枢神経内に集積していることが示唆された．同細胞は活性化によりIFNγとIL-17の両者を産生し，また血液脳関門を通過し，脳・脊髄に浸潤しやすい性質をもつことが分かった．以上からMSの再発に関与する重要な細胞と考えられた．
     複数のケモカイン受容体の発現の組み合わせを調べることにより，疾患に重要な細胞分画を明らかにすることが可能である．現在，他の神経疾患への応用を試みている．

  • 筋萎縮性側索硬化症の呼吸不全に関与する脊髄障害高位の検討
    内藤 絢, 関口 兼司, 永田 格也, 福田 明, 上中 健, 大塚 喜久, 横田 一郎, 千原 典夫, 安井 直子, 久我 敦, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2012, Japanese, (一社)日本神経学会

  • 脊髄小脳失調症6型と31型の臨床症状とMRI拡散テンソル画像の比較
    大塚 喜久, 上田 健博, 永田 格也, 福田 明, 上中 健, 内藤 絢, 横田 一郎, 千原 典夫, 安井 直子, 久我 敦, 関口 兼司, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Dec. 2012, Japanese, (一社)日本神経学会

  • 視神経脊髄炎(NMO)におけるCD138+HLA-DRhigh未熟形質細胞の関与
    千原 典夫, 松岡 貴子, 佐藤 和貴郎, 宮崎 雄生, 三宅 幸子, 林 幼偉, 岡本 智子, 戸田 達史, 荒浪 利昌, 山村 隆
    臨床神経学, Dec. 2012, Japanese, (一社)日本神経学会

  • 13年の寛解期を経て再発した脳卒中様発作で診断された高齢発症MELASの一例
    千原 典夫, 大塚 喜久, 永田 格也, 濱口 浩敏, 関口 兼司, 古和 久朋, 苅田 典生, 戸田 達史
    臨床神経学, Oct. 2012, Japanese, (一社)日本神経学会

  • Activated Plasmablasts Migrate to the Central Nervous System During Relapse of Neuromyelitis Optica
    Chihara N,Oki S,Matsuoka T,Sato W,Lin Y,Okamoto T,Ogawa M,Toda T,Miyake S,Aranami T,Yamamura T
    Federation of Clinical Immunology Societies (FOCIS) 12th annual meeting, Vancouver, Jun. 2012, English
    Poster presentation

  • 免疫性神経疾患に関する調査研究 多発性硬化症/視神経脊髄炎(2)視神経脊髄炎(NMO)におけるplasmablastsの役割
    山村隆, 千原典夫, 千原典夫, 松岡貴子, 佐藤和貴郎, 林幼緯, 岡本智子, 小川雅文, 戸田達史, 三宅幸子, 大木伸司, 荒浪利昌
    免疫性神経疾患に関する調査研究 平成23年度 総括・分担研究報告書, 2012

  • 視神経脊髄炎(NMO)における未熟形質細胞の関与
    千原 典夫, 荒浪 利昌, 林 幼偉, 岡本 智子, 小川 雅文, 戸田 達史, 山村 隆
    臨床神経学, Dec. 2011, Japanese, (一社)日本神経学会

  • NMO-2 視神経脊髄炎(NMO)におけるplasmablastsの関与
    千原 典夫, 荒浪 利昌, 林 幼緯, 岡本 智子, 小川 雅文, 戸田 達史, 山村 隆
    日本神経免疫学会学術集会抄録集, Sep. 2011, Japanese, 日本神経免疫学会

  • 周期性失調症様症状で発症したSCA6の37歳男性例
    堤内 路子, 千原 典夫, 橋本 明子, 木村 哲也, 上坂 義和
    臨床神経学, Aug. 2011, Japanese, (一社)日本神経学会

  • Interleukin 6 Signaling Enhances Anti-aquaporin 4 Autoantibody Production from Plasmablasts in Neuromyelitis Optica
    Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Yamamura T
    Federation of Clinical Immunology Societies (FOCIS) 11th annual meeting, Washington, Jun. 2011, English
    Oral presentation

  • 難治性ニューロパチーの診断技術と治療法の開発に関する研究 慢性炎症性脱髄性多発神経炎におけるT細胞ケモカインの解析
    山村隆, 山村隆, 千原典夫, 冨田敦子, 佐藤和貴郎, 山口広美, 林幼偉, 林幼偉, 小川雅文, 小川雅文, 岡本智子, 岡本智子, 荒浪利昌, 荒浪利昌
    精神・神経疾患研究開発費による研究報告集(2年度班・初年度班) 平成22年度, 2011

  • 免疫性神経疾患に関する調査研究 MS/NMO 病態 視神経脊髄炎(NMO)におけるplasmablastsの役割
    山村隆, 山村隆, 千原典夫, 荒浪利昌, 荒浪利昌, 佐藤和貴郎, 三宅幸子, 三宅幸子, LIN Youwei, LIN Youwei, 小川雅文, 小川雅文, 岡本智子, 岡本智子
    免疫性神経疾患に関する調査研究 平成22年度 総括・分担研究報告書, 2011

  • パーキンソン病の腰曲がりには大腰筋の関与が大きい
    坂本 崇, 古澤 嘉彦, 千原 典夫, 橋本 恵子, 中村 治雅, 山本 敏之, 村田 美穂
    臨床神経学, Dec. 2010, Japanese, (一社)日本神経学会

  • 視神経脊髄炎(NMO)におけるB細胞の役割について
    千原 典夫, 佐藤 和貴郎, 荒浪 利昌, 宮崎 雄生, 三宅 幸子, 岡本 智子, 小川 雅文, 戸田 達史, 山村 隆
    臨床神経学, Dec. 2010, Japanese, (一社)日本神経学会

  • Plasma cell-like B cells produce aquaporin4 autoantibody in neuromyelitis optica
    Norio Chihara, Toshimasa Aranami, Wakiro Sato, Yusei Miyazaki, Sachiko Miyake, Tomoko Okamoto, Masafumi Ogawa, Tatsushi Toda, Takashi Yamamura
    JOURNAL OF NEUROIMMUNOLOGY, Nov. 2010, English, ELSEVIER SCIENCE BV

  • Plasma cell-like B cells produce aquaporin 4 autoantibody in neuromyelitis optica.
    Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Toda T, Yamamura T
    10th International Congress of Neuroimmunology, Sitges (Barcelona), Oct. 2010, English

  • Auto-reactive anti-aquaporin 4 antibodies are secreted from peripheral plasma cell-like B cells in neuromyelitis optica
    Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Yamamura T
    14th Internatinal Congress of Immunology, Kobe, Aug. 2010, English

  • Plasma cell-like B cells produce aquaporin 4 autoantibody in neuromyelitis optica.
    Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Yamamura T
    Neuroimmunology Kyoto Conference 2010, Kyoto, Aug. 2010, English
    [Invited]
    Public discourse

  • 月1回免疫グロブリン少量静注療法が副作用をおさえ寛解維持に有効であった多巣性運動ニューロパチーの1例
    村田 佳子, 岡本 智子, 近土 善行, 千原 典夫, 古澤 嘉彦, 村田 美穂
    臨床神経学, Aug. 2010, Japanese, (一社)日本神経学会, 症例は35歳時左手の筋力低下で発症し、さらに右手筋力低下を呈した多巣性運動ニューロパチーの41歳男性である。免疫グロブリン大量静注療法(high-dose IVIg;0.4g/kg/day 5日間連日投与)をおこない手指筋力の改善をみとめたが、重度の汗疱が出現した。抗アレルギー剤、ステロイド剤の併用にても汗疱の抑制は困難でIVIgを中止したところ、手指筋力の低下が進行した。IVIg0.4g/kgを1日投与に減量し、毎月1回定期的に投与したところ、汗疱の出現はわずかでしかも筋力低下の進行を抑制できた。定期的免疫グロブリン少量静注療法は、IVIgの臨床効果が高い症例では副作用を減らし寛解維持に有効と思われた。(著者抄録)

  • MS/NMO 視神経脊髄炎(NMO)におけるB細胞の役割について
    千原 典夫, 佐藤 和貴郎, 荒浪 利昌, 宮崎 雄生, 三宅 幸子, 岡本 智子, 小川 雅文, 山村 隆
    日本神経免疫学会学術集会抄録集, Mar. 2010, Japanese, 日本神経免疫学会

  • 後頭葉てんかんで発症したミトコンドリア脳筋症の18歳女性例
    千原 典夫, 大矢 寧, 村田 美穂, 後藤 雄一, 渡辺 雅子
    てんかん研究, Jan. 2010, Japanese, (一社)日本てんかん学会

  • 血中動態の多様性からみたL-dopa至適投与量
    千原 典夫, 古澤 嘉彦, 岡本 智子, 塚本 忠, 村田 美穂
    臨床神経学, Dec. 2009, Japanese, (一社)日本神経学会

  • 脳血流シンチでの後頭葉外側のみの血流低下もDLBと診断しうる
    塚本 忠, 近土 善行, 千原 典夫, 村田 佳子, 村田 美穂, 久野 貞子, 葛原 茂樹
    臨床神経学, Dec. 2009, Japanese, (一社)日本神経学会

  • 首下がりがパーキンソン病の嚥下に与える影響
    山本 敏之, 千原 典夫, 近土 善行, 村田 佳子, 中村 治雅, 坂本 崇, 塚本 忠, 村田 美穂
    臨床神経学, Dec. 2009, Japanese, (一社)日本神経学会

  • 磁気センサー型指タッピング計測装置によるパーキンソニズム疾患運動障害の定量的評価
    遠藤 史人, 近土 善行, 千原 典夫, 塚本 忠, 小川 雅文, 神鳥 明彦, 村田 美穂
    臨床神経学, Dec. 2009, Japanese, (一社)日本神経学会

  • VPシャント術後の髄液減少に伴って脊髄障害を呈した70歳男性例
    臼田 治夫, 千原 典夫, 磯尾 紀子, 椎尾 康, 中瀬 浩史
    臨床神経学, Aug. 2008, Japanese, (一社)日本神経学会

  • 関節可動域制限を呈したeosinophilic fasciitisの48歳男性例
    千原 典夫, 藤原 雅代, 磯尾 紀子, 椎尾 康, 中瀬 浩史
    臨床神経学, Jun. 2008, Japanese, (一社)日本神経学会

  • 奇異性脳塞栓症を疑ったEbstein奇形の一例
    千原 典夫, 早川 幹人, 藤原 雅代, 磯尾 紀子, 椎尾 康, 中瀬 浩史
    脳卒中, Mar. 2008, Japanese, (一社)日本脳卒中学会

  • Low dose pergolide induced systemic edema and pleural effusion in a patient with Parkinson's disease
    Chihara, N., Hayakawa, M., Yoshimura, M., Shiio, Y., Nakase, H.
    Clinical Neurology, 2008

  • 無菌性髄膜炎 単純ヘルペス性髄膜炎に伴う脳血管炎の一例
    千原 典夫, 藤原 雅代, 磯尾 紀子, 椎尾 康, 中瀬 浩史
    NEUROINFECTION, Sep. 2007, Japanese, 日本神経感染症学会

  • 関節リウマチに合併した脳梗塞症例の検討
    千原 典夫, 早川 幹人, 藤原 雅代, 東原 真奈, 椎尾 康, 中瀬 浩史
    脳卒中, Mar. 2007, Japanese, (一社)日本脳卒中学会

  • 心不全を呈したミトコンドリア遺伝子異常を有する心筋症(ミトコンドリア心筋症)4例の臨床的検討
    千原 典夫, 土肥 智貴, 増田 純, 藤本 肇, 藤本 陽, 三谷 治夫, 前原 晶子, 大野 実, 石綿 清雄
    日本内科学会雑誌, Feb. 2007, Japanese, (一社)日本内科学会

  • 重症大動脈狭窄症を有した血液透析患者の2剖検例
    千原 典夫, 前原 晶子, 土肥 智貴, 増田 純, 藤本 肇, 藤本 陽, 三谷 治夫, 石綿 清雄, 大野 実
    Circulation Journal, Oct. 2006, Japanese, (一社)日本循環器学会

  • 少量pergolideにて著明な全身性浮腫,胸水貯留をきたしたと考えられるParkinson病の一例
    千原 典夫, 早川 幹人, 吉村 まどか, 椎尾 康, 中瀬 浩史
    臨床神経学, Jan. 2006, Japanese, (一社)日本神経学会

  • 腎癌術後に糖尿病が軽快した長期透析患者の一例
    山形 仁明, 中村 道郎, 千原 典夫, 諏訪部 達也, 乳原 善文, 高市 憲明, 冨川 伸二
    日本泌尿器科学会雑誌, Mar. 2005, Japanese, (一社)日本泌尿器科学会

  • Low dose pergolide induced systemic edema and pleural effusion in a patient with parkinson's disease
    norio chihara

■ Affiliated Academic Society
  • The Japanese Society of Internal Medicine
    Jun. 2004 - Present

  • INTERNATIONAL SOCIETY OF NEUROIMMUNOLOGY
    Nov. 2014

  • JAPANESE SOCIETY FOR NEUROIMMUNOLOGY
    2010

  • THE JAPAN SOCIETY FOR CLINICAL IMMUNOLOGY
    2010

  • JAPANESE SOCIETY OF NEUROLOGY
    2005

■ Research Themes
  • 免疫性神経疾患の神経変性過程を再現する脳内炎症環境モデルの構築
    千原 典夫
    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 01 Apr. 2023 - 31 Mar. 2027

  • Elucidation of neurodegenerative pathology using regulatory gene program of T cells in immune neurological diseases
    千原 典夫, 松本 理器, 古屋敷 智之
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2020 - 31 Mar. 2023
    多発性硬化症(multiple sclerosis; MS)をはじめとする免疫性神経疾患では、病態の核として、T細胞上に発現する共抑制性受容体の機能不全が知られ、慢性的な持続炎症と病態進行の原因となっている可能性がある。MS病態においてCD8陽性(CD8+)T細胞はその神経細胞傷害性機能が想定されてきたが、最近になり炎症病態抑制性の機能が報告され注目されている。申請者は予備実験としてMS患者末梢血を用いて、PD-1陽性(PD-1+)CD8+T細胞の病勢や治療反応性との関連を分析し、急 性期髄液においてはこの細胞亜分画がステロイドパルス療法への反応性の良い群で増加し、寛解期末梢血においてはインターフェロンβ治療によって分化誘導され再発抑制と関連していることを発見した。本研究では申請者が取り組んできた免疫学的解析手法を用いて、疾患修飾治療薬によって良好な経過をとる患者で認められるPD-1を含む共抑制性受容体発現の遺伝子制御機構と進行性病態での役割の解明を目指す。具体的にはMS患者検体を用いて、インターフェロンβ治療によって発現が回復する共抑制性受容体を含む遺伝子群を網羅的遺伝子発現解析によって抽出する。その上で、他の抑制性遺伝子群とも共通の遺伝子プログラムを構築し、その制御機構の鍵となる転写因子を同定する。昨年度は患者CD8+T細胞においてPD-1と共発現する遺伝子について網羅的遺伝子発現解析を行い、複数のT細胞機能低下状態に共通する抑制性遺伝子群を含む遺伝子プログラムを同定した。本年度はこの遺伝子プログラムを直接制御する転写因子をin silico解析で優先順位をつけて絞り込み、その転写因子による遺伝子発現制御によってT細胞の抑制性遺伝子群が獲得されることを同定した。

  • 視神経脊髄炎の個別化医療を目指した免疫寛容システムの解明
    Norio Chihara
    Japan Agency for Medical Research and Development, Practical Research Project for Rare/Intractable Diseases, Apr. 2020 - Mar. 2023, Principal investigator

  • Chihara Norio
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists, Grant-in-Aid for Early-Career Scientists, Kobe University, Apr. 2018 - Mar. 2020, Principal investigator
    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. In advance to this study, the applicant identified and reported a co-inhibitory gene program (co-iGP) commonly found in multiple T cell dysfunctions such as tumor microenvironment and immune tolerance (Chihara N, et al. Nature 2018). Thus, I hypothesized that this co-iGP in T-cells might control inflammatory pathology and prevent neurological impairments of MS patients who had a good clinical course. Indeed, I found that the proportion of a co-inhibotory receptor PD-1 positivity of cerebrospinal fluid CD8 expressing T cells in MS patients correlated with the therapeutic effects. PD-1+CD8+ T-cells from patients who achieved remission by disease modifying treatments suppressed co-cultured other T-cell proliferations, and their gene expression analysis revealed that other co-inhibitory receptors found in co-iGP were expressed.
    Competitive research funding

■ Industrial Property Rights
  • Modulation of novel immune checkpoint targets
    Vijay K. Kuchroo, Ana C. Anderson, Asaf Madi, Norio Chihara, Aviv Regev, Meromit Singer
    特願PCT/US2016/056177, 07 Oct. 2016, The Brigham And Women' s Hospital, Inc., The Broad Institute, Inc., Massachusetts Institute Of Technology ( MIT), 特開WO/2017/069958, 27 Apr. 2017
    Patent right

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