{"created":"2023-07-27T06:53:48.236946+00:00","id":48670,"links":{},"metadata":{"_buckets":{"deposit":"09b423da-0304-415e-8851-38dc53f2f2f6"},"_deposit":{"created_by":18,"id":"48670","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"48670"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00048670","sets":["2812:2813:2834"]},"author_link":["2238","86569"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2000-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"13p.","bibliographicVolumeNumber":"1998-1999","bibliographic_titles":[{"bibliographic_title":"平成11(1999)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"1999 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"CD95(Fas)抗源は血液細胞の生理的アポトーシス細胞死を誘導するシグナルを伝達する分子として同定されたが,lprおよびgldマウスにおける自己免疫様リンパ球増殖症候群がFas,Fasリガンド(FasL)遺伝子異常に起因することが判明したことより,末梢における自己反応性リンパ球や過剰に産生され不用になった成熟リンパ球の排除におけるFas//Fasリガンドシステムによるアポトーシスの重要性が示唆されている.肝脾腫,リンパ節腫大,自己免疫性汎血球減少,高γglobulin血症,TCRαβ陽性CD4陰性CD8陰性T細胞の増加等lpr,gldマウス類似の臨床症状を示す自己免疫リンパ球増殖症候群の3家系4症例においてFas誘導性アポトーシス異常とFas遺伝子変異を解析した.末梢血より単核球及び顆粒球を分離し,PHA活性化T細胞,およびEB virus形質転換B細胞(LCL),顆粒球における抗Fas抗体にて誘導されるアポトーシスを比較検討し,LCLより抽出したRNAをRT-PCRにてFas cDNAを4分画するように設定したプライマーを用い増幅し,そのPCR産物を,Terminator Cycle Sequenxekitを用い塩基配列を検索した.抗Fas抗体を用いた患者由来細胞におけるFas抗原の発現は兄妹例(症例1,2)および症例4では正常であったが,症例3において全く欠如していた.抗Fas抗体により誘導されるアポトーシスは4例とも全く欠如し,患者由来活性化T細胞において抗CD3抗体にて誘導される細胞死も減弱していた.Fas遺伝子異常を解析すると,症例1,2ではintron7のsplicing donorの点突然変異によるexon7-8間に4bpの挿入が認められ,症例3ではexon4欠失のホモ接合体であり,症例4ではdeath domain内1014C-T置換に伴うnonsennse mutationのを認めた.症例1,2,4ではdeath domainを欠く異常Fas抗原によるdominant effectと考えられた.異常遺伝子は症例1,2では母親由来,症例3ではいとこ同士の両親由来であることが判明した.本邦初のFas抗原異常による自己免疫リンパ球増殖症候群を解析しFas抗原の免疫担当細胞のアポトーシスを介し免疫系の恒常性維持に重要な役割を果たすことが再認識された.","subitem_description_type":"Abstract"},{"subitem_description":"Fas-mediated apoptosis and mutation of Fas and Fas ligand (FasL) gene were evaluated in four cases from three families with autoimmune lymphoproliferative syndrome. They showed clinical manifestations of hepatosplenomegaly, Iymphoadenopathy, autoimmune pancytopenia, hypergamma-globulinemia,. Apoptosis induced by anti-Fas antibody was determined PHA-activated T cells, EBV-transformed B cells and freshly isolated granulocytes from patients. Fas and Fas-ligand mRNA from patients' cells was amplified by RT-PCR with primers specific for Fas and Fas-ligand gene and mutations of Fas gene was detected from PCR products. All cells from four cases showed resistance to Fas-induced apoptosis and the surface expression of Fas-receptor was completely diminished on cells from case 3. CD3-indeced activation cell death was also decreased in patients' T cells. Three a different Fas gene mutations were detected. The heterozygous point mutations of intron 7 were detected in case 1 and 2 who are familial cases, resulting in skipping of exon 7 and premature termination. These mutation resulted in production of truncated Fas protein which lacks death domain. Case 3 showed homozygous mutation of intron 3 with lack of exon 4, In case 4, point mutation with exon 9 encoding death domain was detected. All four cases showed an increase of TCRαβ+CD4-CD8- T cells in circulation, which is a specific characteristic in mouse with Fas and FasL mutations.. Familial analysis showed that mutation of Fas gene were inherited from mother in Case 1 and 2 and from both parents in case 3. This is first report of Fas gene mutations in Japan. These results suggest that Fas-mediated apoptosis play pivotal role in maintenance of immune function.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:10670710, 研究期間(年度):1998-1999","subitem_description_type":"Other"},{"subitem_description":"出典：「Fas・Fasリガンド遺伝子異常の分子生物学的解析と遺伝子治療の基礎的検討」研究成果報告書　課題番号10670710\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00054992","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域医学系"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=30204366"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=30204366","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670710/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670710/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10670710/106707101999kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10670710/106707101999kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-10-24"}],"displaytype":"detail","filename":"ME-PR-KASAHARA-Y-kaken 2000-13p.pdf","filesize":[{"value":"306.8 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KASAHARA-Y-kaken 2000-13p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/48670/files/ME-PR-KASAHARA-Y-kaken 2000-13p.pdf"},"version_id":"f8104fdf-4b8a-49e9-b10a-9017d228076f"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"Fas・Fasリガンド遺伝子異常の分子生物学的解析と遺伝子治療の基礎的検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Fas・Fasリガンド遺伝子異常の分子生物学的解析と遺伝子治療の基礎的検討"},{"subitem_title":"Biological analysis of Fas- or Fas ligand gene mutations and basic analysis of gene therapy","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2834"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-10-24"},"publish_date":"2019-10-24","publish_status":"0","recid":"48670","relation_version_is_last":true,"title":["Fas・Fasリガンド遺伝子異常の分子生物学的解析と遺伝子治療の基礎的検討"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:48:24.853447+00:00"}