{"created":"2021-03-01T06:12:07.648659+00:00","id":8125,"links":{},"metadata":{"_buckets":{"deposit":"75745c39-ff59-4b41-bb50-a8ad827c429c"},"_deposit":{"id":"8125","owners":[],"pid":{"revision_id":0,"type":"depid","value":"8125"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00008125","sets":["453:456","471:537:538:877"]},"author_link":["57193","57194"],"control_number":"8125","item_1627361970403":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_7_biblio_info_6":{"attribute_name":"bibliographic_information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-03","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"114","bibliographicPageStart":"105","bibliographicVolumeNumber":"132","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"ja"},{"bibliographic_title":"Niigata Medical Journal","bibliographic_titleLang":"en"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"high-temperature requirement A serine peptidase 1(HTRA1)変異のホモもしくは複合へテロ接合体は遺伝性脳小血管病をおこす．一方，近年，脳小血管病患者においてHTRA1変異のヘテロ接合体が複数例報告された. HTRA1はセリンプロテアーゼであり, 3量体となる事でその活性を調節している．筆者らは,HTRA1変異へテロ接合体で認められたHTRA1変異の病態機序として，変異型HTRA1が優性阻害効果(dominant negative effects: DN)を示すことを提唱してきた．本研究では,既報の変異型HTRA1のDNの有無を解析し,本仮設を検証した．まず，既報の15種(S121R,A123S,R133G,R166C,R166L,A173P,A173T,S284G,S284R,P285Q,F286V,G295R,A321T,L364P,D450H)の変異型HTRA1の精製蛋白を作成し，カゼインを基質としてプロテアーゼ活性を測定した．その結果，11種(S121R,R166C,R166L,A173P,A173T,S284R,P285Q,F286V,G295R,A321T,L364P)で，野生型HTRA1と比較して有意な低下を認めた．次に，野生型HTRA1と変異型HTRA1を混合しプロテアーゼ活性を測定したところ，5種(R166L,A173P,A173T,S284R,G295R)でDNを認めた．さらに，ゲル濾過クロマトグラフィーにて3量体形成能を解析したところ, DNを認める5種の変異のうち，4種(R166L,A173P,A173T,G295R)で3量体の形成不全を認めた．最後にDNを認めたヘテロ接合体変異例17例とDNを認めないヘテロ接合体変異例9例の臨床像を比較したところ, DNを認める群で症候性脳小血管病の頻度が有意に高かった(76.5% vs 33.3%, p < 0.046).以上の結果から, DNを認める変異型HTRA1は，ヘテロ接合体で症候性脳小血管病の発症に寄与するという仮説が支持された．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"57194","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Uemura, Masahiro"}]}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会","subitem_publisher_language":"ja"},{"subitem_publisher":"The Niigata Medical Society","subitem_publisher_language":"en"}]},"item_7_select_19":{"attribute_name":"item_7_select_19","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_7_source_id_11":{"attribute_name":"item_7_source_id_11","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"00290440","subitem_source_identifier_type":"PISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"上村, 昌寛","creatorNameLang":"ja"},{"creatorName":"Uemura, Masahiro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"57193","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-06"}],"displaytype":"detail","filename":"132(3)_105-114.pdf","filesize":[{"value":"5.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"132(3)_105-114.pdf","url":"https://niigata-u.repo.nii.ac.jp/record/8125/files/132(3)_105-114.pdf"},"version_id":"d0e18bd6-5874-4e0b-ba12-1bc156479032"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"脳小血管病","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"HTRA1","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"ヘテロ接合体変異","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"優性阻害効果","subitem_subject_language":"ja","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"item_resource_type","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"脳小血管病患者でへテロ接合性に認められたhigh-temperature requirement A serine peptidase 1(HTRA1)変異の病的意義の検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"脳小血管病患者でへテロ接合性に認められたhigh-temperature requirement A serine peptidase 1(HTRA1)変異の病的意義の検討","subitem_title_language":"ja"},{"subitem_title":"Association of Heterozygous Mutations in high temperature requirement A serine peptidase 1 and Cerebral Small Vessel Disease","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","877"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-09-19"},"publish_date":"2018-09-19","publish_status":"0","recid":"8125","relation_version_is_last":true,"title":["脳小血管病患者でへテロ接合性に認められたhigh-temperature requirement A serine peptidase 1(HTRA1)変異の病的意義の検討"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2025-07-11T02:38:28.502077+00:00"}