WEKO3
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アセチルコリン受容体と重症筋無力症の免疫、生化学および治療に関する研究
https://doi.org/10.24517/00067567
https://doi.org/10.24517/000675670cdf3b3a-9423-4069-9ed9-ebbe3ccbdd0e
名前 / ファイル | ライセンス | アクション |
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HO-PR-TAKAMORI-M-kaken 1993-4p.pdf (222.1 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2022-11-04 | |||||
タイトル | ||||||
タイトル | アセチルコリン受容体と重症筋無力症の免疫、生化学および治療に関する研究 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Immunological, Biochemical and Therapeutical Research in Acetylcholine Receptor and Myasthenia Gravis | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00067567 | |||||
ID登録タイプ | JaLC | |||||
著者 |
高守, 正治
× 高守, 正治 |
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著者別表示 |
Takamori, Masaharu
× Takamori, Masaharu |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学医学部・附属病院・神経内科 | |||||
書誌情報 |
平成2(1990)年度 科学研究費補助金 一般研究(B) 研究成果報告書概要 en : 1990 Fiscal Year Final Research Report Summary 巻 1988 – 1990, p. 4p., 発行日 1993-08-11 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 重症筋無力症病態解明と新しい治療法開拓のため、本病成立にかゝわる免疫反応の標的であるアセチルコリン受容体(AChR)を分子レベルから研究した。1.重症筋無力症発病機構の中で主役の一つを演ずるブロッキング抗体(AChRとAChとの結合阻事作用)のAChR分子構造上の標的を、一連のアミノ酸配列の中のα183ー200領域と特定、その合成ペプチドは高いACh結合能を有し、また本ペプチドを抗原としてラットを免疫すれば、疾患モデルを作出しうることを証明した。この領域に対する抗ペプチド抗体は、ヒト筋無力症患者血中にも証明できた。本領域の合成ペプチドを固定化した吸着剤と、体外楯環中の患者血液とを反応させ(処理後の血液は再び患者体内へ還流)、有意な臨床効果を得、分子レベルからの本病治療に資した。2.筋無力症発病機構の中でのもう一つの主役であるバインディング抗体(AChR崩壊促進、補体介右性細胞膜破壊作用)のAchR分子構造上の標的として、α67ー76,α70ー90,α125ー147を推定、それぞれの合成ペプチドを抗原としてラットを免疫、疾患モデルを作出し得、これを実証した。各領域に対する抗ペプチド抗体は、ヒト筋無力症血中にも証明でき、将来の免疫吸着療法の具体化に展望をひらいた。3.抗体産生ヘルパ-T細胞認識領域としてAChRαサブユニットのアミノ酸配列の中から、ヒトの場合19カ所を特定したが、抗体反応領域とは一致していなかった。4.重症筋無力症発症は、AChR分子構造の中で、βタ-ン構造をとるB細胞認識領域と、αヘリックス構造のT細胞認識領域の、両領域の免疫学的連係認識の上に成立するとの観点から、両者を種々のかたちで連結したり、人工的配列のアミノ酸を両者間に介在せしめたモデルペプチドを合成、より高い免疫原性、より強い抗体認識性を示す人工的な分子立体構造を特定して、特定の治療用人工抗原材製に資ずる情報を得た。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Upon the availability of amino acid sequences and transmembrane topography of acetylcholine receptor (AChR) alpha-subunit, the research attempted to localize myasthenic domains on AChR, such as the sites recognized by the "blocking antibody" which prevents the binding of ACh with AChR and by the "binding antibody" which accelerates the degradation of AChR, by use of peptides synthesized referring to AChR molecular structure, resulting in the following : (1) The synthetic peptide, alpha183-200, was immunogenic in the induction of myasthenia in animals and antigenic in the detection of antibody in human myasthenic patients. (2) Myasthenic patients treated with plasmaperfusion by use of the synthetic peptide (alpha183-200)-bound adsorbent showed clinical improvement in association with the reduction of corresponding anti-peptide antibody and anti-native AChR blocking antibody in sera. (3) Synthetic peptides, alpha67-76, alpha70-90 and alpha125-147, were stimulatory to the induction of myasthenia in animals, and were useful to detect myasthenic antibody in humman myasthenic sera. (4) Nineteen segments in the molecular structure of ACha alpha-subunit were found to be T-cell epitopes, but they were not potent to stimulate B-cells. (5) Artificially formed peptides were synthesized by coupling natural AchR peptides and theoretical amino acid sequences based on the concept that the induction of myasthenia gravis depends on linked recognition of the B-cell epitope expected at beta-turn structure and the T-cell epitope expected at amphipathic alpha-helical structure. These conformationally modified AChR peptides were more immunogenic and antigenic than AChR peptides of natural sequences, and provided a provision for the antigenspecific therapy in myasthenia qravis. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:63480215, 研究期間(年度):1988 – 1990 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:研究課題「アセチルコリン受容体と重症筋無力症の免疫、生化学および治療に関する研究」課題番号63480215 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-63480215/634802151990kenkyu_seika_hokoku_gaiyo/)を加工して作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/search/?kw=60039815 | |||||
関連名称 | https://kaken.nii.ac.jp/ja/search/?kw=60039815 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-63480215/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-63480215/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-63480215/634802151990kenkyu_seika_hokoku_gaiyo/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-63480215/634802151990kenkyu_seika_hokoku_gaiyo/ |