Effect of autoantihody from myasthenia gravis and immunosuppressant on gene expression of skeletal muscle
| Project/Area Number |
16590818
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIKAWA Hiroaki Kanazawa University, Health Service Center, Professor (10272981)
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| Co-Investigator(Kenkyū-buntansha) |
IWASA Kazuo Kanazawa University, Graduate of School of Medicine, Associate Professor (10345613)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Myasthenia gravis / Thymus / Thymoma / Interleukin -12 / Autoantihndies / 抗サイトカイン抗体 / IL-12 p40 / IL-12 p70 / IL-12p40 / IL-12p70 / アセチルコリン受容体 / 細胞内カルシウム / リアノジン受容体 / IP3受容体 / FK506 / 横紋筋 / 平滑筋 |
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| Research Abstract |
Myasthenia gravis (MG) is thought to be a disorder targeting at the acetylcholine receptor (AChR) on postsynaptic membrane of neuromuscular junction (NMJ). One of clinical characteristics of MG is high prevalence of thymic abnormality as high as 90% of patients. About 80% of patients have thymic follicular hyperplasia and 20% have thymoma. The patients with thymoma are refractory to therapy, i.e., they need to receive high amount of steroid for treatment. We measured AChR antibody, cytokines and antibodies against cytokines for studying the autoimmunity of MG patients with thymoma. For measurement of AChR antibodies, we used immunoprecipitation method. For measurement of cytokines, enzyme-linked immunosorbent assay (ELISA) was applied. For measurement of antibodies against cytokines, the modified ELISA was utilized. As a result, antibodies against interleukin (IL)-12 p70 were high in patients with thymoma with or without MG. IL-12 p40 and anti-IL-12 p40 antibodies elevated in sera from MG patients with thymoma. Additionally, we developed assay system for detecting antibodies against ryanodine receptor (RyR) that have a role in excitation-contraction (E-C) coupling of skeletal muscle. The method use whole protein of RyR instead to synthetic peptide, and is more sensitive and specific than ELISA system using synthetic peptide. Using detection system for RyR antibodies, we found that a group of MG patients with thymoma have autoantibodies against both AChR and RyR. Therefore, the pathological targets of MG patients with thymoma are synaptic transmission (AChR) and E-C coupling (RyR).
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Is excitation-contraction coupling impaired in myasthenia gravis2007
Author(s)
Nakata, M., Kuwabara, S., Kawaguchi, N., Takahashi, H., Misawa, S., Kanai, K., Tamura, N., Sawai, S., Motomura, M., Shiraishi, H., Takamori, M., Maruta, T., Yoshikawa, H., Hattori, T
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Journal Title
Clin Neurophysiol 118
Pages: 1144-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravis2007
Author(s)
Shibata-Hamaguchi, A., Samuraki, M., Furui, E., Iwasa, K., Yoshikawa, H., Hayashi, S., Yamada, M
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Journal Title
Acta Neurol Scand 116
Pages: 406-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Elevation of IL-12 p40 and its antibody in myasthenia gravis with thymoma2006
Author(s)
Yoshikawa, H., Sato, K., Edahiro, S., Furukawa, Y., Maruta, T., Iwasa, K., Watanabe, H., Takaoka, S., Suzuki, Y., Takamori, M., Yamada, M
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Journal Title
J Neuroimmunol 175
Pages: 169-75
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction2006
Author(s)
Pittrock, SJ., Yoshikawa, H., Ahlskog, JE., Tisch, SH., Benarroch, EE., Kryzer, TJ., Lennon, VA
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Journal Title
Mayo Clin Proc 81
Pages: 1207-14
Description
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[Journal Article] Elevation of IL-12 p40 and its antibody in myasthenia gravis with thymoma.2006
Author(s)
Hiroaki Yoshikawa, Katsuaki Sato, Shigeki Edahiro, Yutaka Furukawa, Takahiro Maruta, Kazuo Iwasa, Hideto Watanabe, Shizuka Takaoka, Yasuhiro Suzuki, Masaharu Takamori, Masahito Yamada
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Journal Title
Journal of Neuroimmunology (in press)
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[Journal Article] A novel immunomodulator, FTY720, prevents development of experimental autoimmune myasthenia gravis in C57BL/6 mice.2006
Author(s)
Kohno T, Isuji T, Hirayama K, Iwatsuki R, Hirose M, Watabe K, Yoshikawa H, Kohno T, Matsumoto A, Fujita T, Hayashi M.
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Journal Title
Mol Pharm Bull 28
Pages: 736-739
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[Journal Article] A novel immunomodulator, FTY720, prevents development of experimental autoimmune myasthenia gravis in C57BL/6 mice2005
Author(s)
Kohno, T., Tsuji, T., Hirayama, K., Iwatsuki, R., Hirose, M., Watabe, K., Yoshikawa, H., Kohno, T., Matsumoto, A., Fujita, T., Hayashi, M
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Journal Title
Mol Pharm Bull 28
Pages: 736-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Anti-ryanodine receptor antibodies and FK506 in myasthenia gravis2004
Author(s)
Takamori, M., Motomura, M., Kawaguchi, N., Nemoto, Y., Hattori, T., Yoshikawa, H., Otsuka, K
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Journal Title
Neurology 62
Pages: 1894-1896
Description
「研究成果報告書概要(欧文)」より
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