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Molecular Immunology in Myasthenia Gravis studied by the Use of Conformation-Modified Synthetic Peptides of Acetylcholine Receptor

Research Project

Project/Area Number 03454239
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKanazawa University

Principal Investigator

TAKAMORI Masaharu  Kanazawa University School of Medicine ; Department of Neurology ; Professor, 医学部, 教授 (60039815)

Co-Investigator(Kenkyū-buntansha) NITTA Eishun  Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 助手 (50251947)
SAKATO Shunichi  Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 助手 (10142275)
IDE Yoshihiko  Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 講師 (10100835)
奥村 誠一  金沢大学, 医学部附属病院, 助手 (60152435)
松原 四郎  金沢大学, 医学部, 講師 (00143884)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsAcetylcholine receptor / Synthetic peptides / Antibody / Immune cells / Myasthenia gravis / 血液浄化療法 / 抗体 / 免疫原 / 疾患モデル動物
Research Abstract

Myasthenogenic regions in the acetylcholine receptor (AChR)alpha-subunit were studied in view of the conformation-dependent B-cell epitope expected at beta-turn and the MHC class II-restricted T-cell epitope expected at alpha-helix. Torpedo AChR alpha67-76 and alpha107-116 were synthesized as the main immunogenic region and the site specific for T-cell epitope in Lewis rat, respectively. Model peptides, synthesized by combining these natural sequence segments or by intervening the segment aligned as NPGG in natural sequence segments, were tested in terms of antigenic conformation. The model peptide, alpha107-116.alpha67-76.alpha107-116, was potently immunogenic in the induction of the animal model of myasthenia, accomplanied by the anti-peptide antibody cross-reactive with the native AChR.High antigenicity in antibody assays for vaious peptide- and native AChR-immunized rats was found when the model peptides, alpha107-116.alpha67-76 and/or alpha107-116. NPGG.aplha67-76, were used for measurement as antigens. Since none of these model peptides was reactive with antibody in human myasthenics, peptides were therefore designed to conforom to the antigen appropriate for binding with human myasthenic antibody. As the result, 4 model peptides, CKGGLR.alpha67-76.C,KKC.alpha63-77.C, KKC.alpha62-77, and KKCalpha 61-77-C, were potently reactive with monoclonal myasthenic antibody and useful for detecting antibody in human myasthenics.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (82 results)

All Other

All Publications (82 results)

  • [Publications] 高守正治: "A synthetic peptide,Torpedo californica α183-200,of the acetylcholine receptor as a tool for immunoadsorption via plasma perfusion in myasthenia gravis" Artificial Organs Today. 1. 53-60 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "臓器特異的自己免疫疾患動物モデルにおける最近の進歩-重症筋無力症" 臨床免疫. 23. 981-993 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "重症筋無力症におけるアセチルコリン受容体合成ペプチドを吸着剤とした免疫療法の検討" 集中治療. 3. 319-320 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "免疫性プペチド-高次構造と抗体産生に関する問題点" 免疫藥理. 9. 134-135 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "重症筋無力症" 臨床と研究. 68. 1019-1028 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design:An approach to antigenic synthetic peptides" Journal of the Neurological Sciences. 109. 82-187 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "自己免疫疾患とカルシウム" Clinical Neuroscience. 10. 449-452 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "重症筋無力症とLambert-Eaton筋無力症候群" Clinical Neuroscience. 10. 665-670 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 井手芳彦: "本邦臨床統計集II筋疾患2.重症筋無力症" 日本臨床. 50. 186-193 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "重症筋無力症の治療と予後" 日本医事新報. 3564号. 117 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "神経疾患診断-ガイドラインと検査計画:重症筋無力症" 臨床医. 18. 1936-1940 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "重症筋無力症" ブレインナーシング. 8. 427-435 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "Stereoview of conformation and myasthenogenicity in synthetic peptides of acetylcholine receptor α-subunit" Annals of New York Academy of Sciences. 681. 168-171 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "Muscarinic receptor-mediated modulation of acetylcholine release in mice with passively transferred Lambert-Eaton myasthenic syndrome" Annals of New York Academy of Sciences. 681. 415-417 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守正治: "Atropine modulates presynaptic function in mice with passively transferred Lambert-Eaton myasthenic syndrome" Muscle & Nerve. 16. 115-116 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "カルシウムチヤネル関連蛋白質と筋無力症候群" Molecular Medicine. 30. 914-915 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "アセチルコリン受容体分子構造と抗体" 医学のあゆみ. 165. 102-106 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "重症筋無力症" nano GIGA. 2. 1126-1133 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "重症筋無力症" JOHNS. 9. 978-984 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "重症筋無力症" 現代医療. 26. 103-108 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats (印刷中)" Annals of Neurology. 34. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 井手 芳彦: "Treatment of myasthenia Gravis with a Specific Immunoadsorbent bound to acetylcholine receptor peptide α183-200.In:Therapeutic Plasmapheresis" ICAOT Press(Cleveland,USA), 6 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 分担執筆: "臨床神経内科学第2版" 南山堂(東京), 21 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "最新医工学治療-吸着治療マニュアル" 金原出版(東京), 8 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 分担執筆: "現代病理学大系21A" 中山書店(東京), 20 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 分担執筆: "レセプター-基礎と臨床" 朝倉書店(東京), 10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 分担執筆: "イオンチヤネル-細胞機能への関与とその異常" メジカルビュー社(東京), 12 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "モダンクリニカルポイント-重症筋無力症の分子レベルからのアプローチ" 金原出版(東京), 2 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "今日の治療指針" 医学書院(東京), 2 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "内科学第6版" 朝倉書店(東京) (予定), 40 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "新筋肉病学" 南江堂(東京) (予定), 50 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "臨床神経内科学 第3版" 南山堂(東京) (予定), 35 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "血液淨化療法" 医学書院(東京) (予定), 10 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "図説病態-内科講座 第11巻神経-2" メジカルビュー社(東京) (予定), 10 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治 (分担執筆): "内科治療ガイド" 文光堂(東京), 6 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Takamori, Seiichi Okumura and Yoshihiko Ide: "A synthetic peptide, Torpedo californica alpha183-200, of the acetylcholine receptor as a tool for immunoadsorption via plasma perfusion in myasthenia gravis." Artif.Organs Today. 1. 53-60 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Takamori, Toshio Hamada and Seiichi Okumura: "Myasthenogenicity in the main immunologic region of acetylcholine receptor as modified by conformational design : an approach to antigenic synthetic peptides." Journal of the Neurological Sciences. 109. 182-187 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Takamori: "Stereoview of conformation and myasthenogenicity in synthetic peptides of acetylcholine receptor alpha-subunit." Annals of New York Academy of Sciences. 681. 168-171 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Takamori: "Muscarinic receptor-mediated modulation of acetylcholine release in mice with passively transferred Lambert-Eaton myasthenic syndrome." Annals of New York Academy of Sciences. 681. 415-417 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Takamori, kenichi Sakajiri and Toshio Hamada: "Atropine modulates presynaptic function in mice with passively transferred Lambert-Eaton myasthenic syndrome." Muscle & Nerve. 16. 115-116 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masaharu Tamamori, Toshio Hamada, Kiyonobu Komai, Masami Takahashi and Akira Yoshida: "Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats." Annals of Neurology. 34 : (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高守 正治: "Stereoview of conformation and myasthenogenicity in synthetic peptides of acetylcholine receptor α-subunit" Annals of New York Academy of Sclences. 681. 168-171 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "Muscarinic receptor-mediated modulation of acetylcholine release in mice with passively transferred Lambert-Eaton myasthenic syndrome" Annals of New York Academy of Sclences. 681. 415-417 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "Atropine modulates presynaptic function in mice with passively transferred Lambert-Eaton myastbenic syndrome" Muscle & Nerve. 16. 115-118 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "カルシウムチヤネル関連蛋白質と筋無力症候群" Molecular Medicine. 30. 914-915 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "アセチルコリン受容体分子構造と抗体" 医学のあゆみ. 165. 102-106 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "重症筋無力症" nano GIGA. 2. 1126-1133 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "重症筋無力症" JOHNS. 9. 978-984 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "重症筋無力症" 現代医療. 26. 103-108 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats" Annals of Neurology. 35(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "レセプター-基礎と臨床(分担執筆)" 朝倉書店, 10 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "イオンチヤネル-細胞機能への関与とその異常(分担執筆)" メジカルレビュー社, 11 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "モダンクリニカルポイント-重症筋無力症の分子レベルからのアプローチ(分担執筆)" 金原出版, 2 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "今日の治療指針1993(分担執筆)" 医学書院, 2 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "内科治療ガイド(分担執筆)" 文光堂(印刷中), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "内科学 第6版(分担執筆)" 朝倉書店(予定:40), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "新節肉病学(分担執筆)" 南江堂(予定:50), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "臨床神経内科学 第3版" 南山堂(予定:35), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "血液淨化療法(分担執筆)" 医学書院(予定:10), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "図説病態内科講座 第11巻 神経-2(分担執筆)" メジカルビュー社(予定:10), (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高守 正治: "Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design:an approach to antigenic synthetic peptides" Jounral of the Neurological Sciences. 109. 82-187 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "重症無力症とLambert-Eaton筋無力症修群" Cliuical Neuroscience. 10. 665-670 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "Stereo View of conformation and mysthenogenicity in synthetic peptides of acetylcholine Receptor -subunit" Annats of New York Academy of Science. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "Muscarinic receptor-mediated modulation of acetylcholine release in mice with passively transferred Lambert-Eaton myasthenic syndrome" Annals of New York Academy of Science. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "Atropine modulates presynaptic function in mice with passively transferred Lambert-Eaton myasthenic syndrome" Muscle & Nerve. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "マセチルコリン受容体と抗体" 医学のゆみ. 165. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "最新医工学治療ー吸着療法マニュアル" 金原出版, 8 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "現代病理学大系21A-11(重症筋無力症)" 中山書店, 20 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高守 正治: "A synthetic peptide,Torpedo californica α183ー200,of the acetylcholine receptor as a tool for immunoadsorption via plasma perfusion in myasthenia gravis" Artificial Organs Today. 1. 53-60 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "臓器特異的自己免疫疾患動物モデルにおける最近の進歩ー重症筋無力症" 臨床免疫. 23. 981-993 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "重症筋無力症におけるアセチルコリン受容体合成ペプチドを吸着剤とした免疫療法の検討" 集中治療. 3. 319-320 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "免疫性ペプチドー高次構造と抗体産生に関する問題点" 免疫薬理. 9. 134-135 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "重症筋無力症" 臨床と研究. 68. 1019-1028 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design" Journal of the Neurological Scineces. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "Muscarinic receptorーmediated modulation of acetylcholine release in mice with passively transferred LambertーEaton myasthenic syndrome" Muscle and Nerve. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "神経と免疫ー重症筋力症とLambertーEaton筋無力症候群" Clinical Neuroscience. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 井手 芳彦: "Treatment of Myasthenia Gravis with a specific immunoadsorbent bound to acetylcholine receptor peptide α183ー200 In:Therapeutic Plasmapheresis" ICAOT Press(Cleveland,USA), 6 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "臨床神経内科学(第2版)(分担執筆)" 南山堂(東京), 22 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "シリ-ズ最新医工学治療ー吸着治療マニュアル" 金原出版(東京), (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "新筋肉病学(分担執筆)" 南江堂(東京), (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "レセプタ-基礎と臨床(分担執筆)" 朝倉書店(東京), (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 高守 正治: "現代病理学大系第21巻A(分担執筆)" 中山書店(東京), (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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