{"created":"2023-07-25T08:03:07.545294+00:00","id":1029,"links":{},"metadata":{"_buckets":{"deposit":"fdfc91f4-6b5c-4f99-8119-c7e6b400f128"},"_deposit":{"created_by":3,"id":"1029","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"1029"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00001029","sets":[]},"author_link":["6519","117817","117818","117815","117814","117816","6517","6518","117813"],"item_8_alternative_title_18":{"attribute_name":"別言語のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Comprehensive regulatory system of PAMPs/DAMPs by TM-PC/EPCR system"}]},"item_8_alternative_title_19":{"attribute_name":"タイトルよみ","attribute_value_mlt":[{"subitem_alternative_title":"PAMPs-DAMPs ノ ホウカツテキ セイギョ システム トシテノ TM-PC/EPCR ソウチ"}]},"item_8_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2013-06-21"}]},"item_8_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"2012-2012年度科学研究費助成事業(科学研究費補助金(挑戦的萌芽研究)研究成果報告書　課題番号：24659798　研究代表者：丸山征郎(鹿児島大学・大学院医歯学総合研究科・特任教授)","subitem_description_type":"Other"},{"subitem_description":"培養血管内皮細胞上のトロンボモジュリン（TM）分子のN末端レクチン様ドメインにはDAMPs：HMGB1, histones が, PAMPs：エンドトキシン（LPS）が結合して、それぞれそれらの活性を制御した。そこで今回の研究では特にHMGB1のダイナミズムについて研究した。TMのN末端のレクチン様ドメインに結合したHMGB1は、トロンビン・TM複合体によって、N末端のArg(10)-Gly(11)部位で切断されHMGB1は遊離されて、活性の低下したdes-HMGB1が生成された。このdes体はintact HMGB1の受容体（RAGE, TLRs-2,-4）への結合を阻害したことから、体内ではHMGB1とその受容体系のネガティブフィードバック系を形成しているものと推定された。そこでこのdes-HMGB1を即位的に認識するELISAを樹立した。このアッセイ法は９０％のdes-HMGB1を検出したが、１０％はintact HMGB1がコンタミネーションを起こしていた。本方法で諸疾患、特に遺伝子組換え体のＴＭで治療された患者の血中のdes-HMGB1した。遺伝子組換えTM投与で、速やかにdes-HMGB1が上昇する患者検体が観られた。しかし遺伝子組換えTMの投与でもdes-HMGB1の上昇しない症例、あるいはただちに低下する例などが観察され、遺伝子組換えTM治療に対し、レスポンダーと非レスポンダーがあること、あるいはdes-HMGB1の体内ターンオーバーの個体差の存在が推定された。","subitem_description_type":"Other"},{"subitem_description":"Endothelial thrombomodulin(TM) bounds DAMPs(Damage Associated Molecular Patterns);HMGB1,a representative DAMPs, histones. Moreover TM also bounds PAMPs(Pathogen Associated Molecular Patterns) ;lipopolysaccaride(LPS), a representative PAMPs, onto the lectin-like domain of the molecule and neutralizes their cytopathic activities, including proinflammatory and procoagulant activities. HMGB1 bound to TM, degraded by thrombin/TM complex and generated the N-terminus deleted HMGB1, named as des-HMGB1. Des-HMGB1 bound onto the receptors RAGE and TLR2-2, -4. However the binding affinity was weak compared to intact HMGB1, suggesting des-form of the molecule may configure a negative feedback loop among HMGB1 and its receptors regulating the diverse activities of HMGB1. Based on the findings, assay of des-HMGB1.may provide significant information in such morbid states including Disseminated Intravascular Coagulation(DIC), sepsis, systemic inflammatory response sybdrome(SIRS) and so on. Therefore we tried to establish specific assay method of des-HMGB1. We got specific monoclonal antibodies to react with the des-HMGB1. Using the monoclonal antibody, we established specific enzyme linked immune sorbent assay(ELISA). The ELISA successfully detected des-HMGB1 with 10% contamination of intact form. Des-HMGB1 was increased the serum from DIC, especially treated with recombinant TM. However the increased des-HMGB1 was decreased rapidly suggesting the rapid turn-over of the des-form. Moreover some patients showed no increased in des-HMGB1 even with recombinant TM treatment, suggesting of the presence or non-responder cases. Thus assessment of des-HMGB1 may be expected to provide a novel information in the DIC, SIRS, sepsis and so on with or without treatment.","subitem_description_type":"Other"}]},"item_8_full_name_2":{"attribute_name":"著者よみ","attribute_value_mlt":[{"nameIdentifiers":[{}],"names":[{"name":"マルヤマ, イクロウ"}]},{"nameIdentifiers":[{}],"names":[{"name":"イトウ, タカシ"}]},{"nameIdentifiers":[{}],"names":[{"name":"ハシグチ, テルト"}]}]},"item_8_full_name_3":{"attribute_name":"別言語の著者","attribute_value_mlt":[{"nameIdentifiers":[{}],"names":[{"name":"MARUYAMA, Ikuro"}]},{"nameIdentifiers":[{}],"names":[{"name":"ITO, Takashi"}]},{"nameIdentifiers":[{}],"names":[{"name":"HASHIGUCHI, Teruto"}]}]},"item_8_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"鹿児島大学"}]},"item_8_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"494.27","subitem_subject_scheme":"NDC"}]},"item_8_text_24":{"attribute_name":"公開者よみ","attribute_value_mlt":[{"subitem_text_value":"カゴシマ ダイガク"}]},"item_8_text_25":{"attribute_name":"公開者別名","attribute_value_mlt":[{"subitem_text_value":"Kagoshima University"}]},"item_8_text_41":{"attribute_name":"科研費番号 ","attribute_value_mlt":[{"subitem_text_value":"24659798"}]},"item_8_version_type_14":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"丸山, 征郎"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"伊藤, 隆史"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"橋口, 照人"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-10-27"}],"displaytype":"detail","filename":"24659798.pdf","filesize":[{"value":"180.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"24659798.pdf","url":"https://ir.kagoshima-u.ac.jp/record/1029/files/24659798.pdf"},"version_id":"5eb9e38d-a8ec-4a56-845f-7b5329783c14"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"PAMPs","subitem_subject_scheme":"Other"},{"subitem_subject":"DAMPs","subitem_subject_scheme":"Other"},{"subitem_subject":"トロンボモジュリン","subitem_subject_scheme":"Other"},{"subitem_subject":"プロテインC","subitem_subject_scheme":"Other"},{"subitem_subject":"HMGB1","subitem_subject_scheme":"Other"}]},"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":"Pamps-DAMPsの包括的制御システムとしてのTM-PC/EPCR装置","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Pamps-DAMPsの包括的制御システムとしてのTM-PC/EPCR装置"}]},"item_type_id":"8","owner":"3","path":["80"],"pubdate":{"attribute_name":"公開日","attribute_value":"2013-10-01"},"publish_date":"2013-10-01","publish_status":"0","recid":"1029","relation_version_is_last":true,"title":["Pamps-DAMPsの包括的制御システムとしてのTM-PC/EPCR装置"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-12-25T07:18:45.429304+00:00"}