{"created":"2023-07-27T06:51:00.214307+00:00","id":44230,"links":{},"metadata":{"_buckets":{"deposit":"817566d3-674e-4c5d-bb8b-7723c5fe4a20"},"_deposit":{"created_by":18,"id":"44230","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44230"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044230","sets":["2812:2813:2831"]},"author_link":["70288","49"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2003-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"10p.","bibliographicVolumeNumber":"1999-2002","bibliographic_titles":[{"bibliographic_title":"平成14(2002)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2002 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":"本研究は、肝臓での炎症の遷延化過程に関与している内因性因子を同定するために、種々のマウスの肝障害モデルの分子病理学的解析を行い、以下の研究成果を得た。\n1)インターフェロン(IFN)-γが炎症性サイトカイン産生と炎症性細胞の浸潤を制御することを通して、Propionibacterium acnes (P. acnes)にて感作後のリポ多糖類投与による急性肝障害ならびにアセトアミノフェン投与による急性肝障害の発症過程に、垂要な役割を果たしていることを証明した。\n2)四塩化炭素反復投与による肝線維症の発症過程で、IL-6は線維化過程の促進に働く一方で、肝細胞の血清蛋白産生能の保持の両面に働くことを示唆する結果を得た。\n3)Dimethylnitrosamine反復投与時、TNFレセプターp55を介したシグナルによって、クッパー細胞・伊東細胞の集積が起き、その結果線維化が生じる可能性が示唆された。\n4)脾臓内への腫瘍細胞接種によっておきる肝転移過程において、肝臓内でのTNF-αの発現増強が起き、その結果起きる肝類洞血管内皮上でのVCAM-1発現の増強が、肝転移巣形成過程に密接に関与していることが示唆された。\n5)ヒト肝癌組織では、肝癌組織内で産生されるIL-1がautocrineあるいはparacrine的にCCケモカインの一つであるCCL3の産生を誘導し、これが肝癌細胞などで恒常的に発現しているCCL3の特異的レセプターであるCCR1に作用する可能性が示唆された。\nこれらの炎症モデルの発症と遷延化に関与している内因性因子を検索するために、炎症モデルでの野生型マウスと種々の遺伝子欠損マウスとの間での遺伝子発現パターンの差異を検討している。","subitem_description_type":"Abstract"},{"subitem_description":"In order to identify an endogenous bioactive substance(s) which are involved in the chronic phases of inflammation in liver, we analyzed several liver dysfunction models in mice from molecular pathological viewpoints.\n#1. We proved that interferon (IFN)-γ regulated the production of pro-inflammatory cytokines and the infiltration of inflammatory cells including neutrophils and macrophages, thereby contributing to the development of lipopolysaccharide (LPS)-induced acute liver injury in Propioniobaciterium acnes-primed mice and acetaminophen-induced acute fatal liver dysfunction.\n#2. We obtained the evidence to suggest that interleukin (IL)-6 have bifacial roles in carbon tetrachloride-induced chronic liver fibrosis; induction of fibrogenic process and maintenance of the hepatocyte capacity to produce serum proteins such as albumin, by up-regulating the expression of a potent fibrogenic factor, transforming growth factor-β_1 and hepatocyte growth factor, respectively.\n#3. We have provided evidence that tumor necrosis factor receptor p55-mediated signals regulated the accumulation of Kupffer and Ito cells, thereby inducing liver fibrosis.\n#4. We observed that intrasplenic injection of tumors induced TNF-α expression and subsequent vascular adhesion molecule-1 expression in sinusoidal endothelial cells in liver, thereby inducing liver metastasis.\n#5. We observed that CCL3, induced by endogenously produced IL-1, might interact with its specific receptor, CCR1, constitutively expressed on hepatoma cells, in human hepatoma tissues.\nWe are in the process to analyze the gene expression patterns between wild-type and various types of cytokine-related gene-deficient mice in the above mentioned inflammation models, in order to identify the molecule(s) which is crucially involved in the development of chronic liver inflammation.","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:11470516, 研究期間(年度):1999-202","subitem_description_type":"Other"},{"subitem_description":"出典：「肝障害の遷延化に関与する因子の検索に基づく、慢性肝障害の新規の早期診断法の開発」研究成果報告書　課題番号11470516\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":"10.24517/00050572","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=30182067","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11470516/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-11470516/114705162002kenkyu_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":"2018-04-19"}],"displaytype":"detail","filename":"CA-PR-MUKAIDA-N-kaken 2003-10p.pdf","filesize":[{"value":"713.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-MUKAIDA-N-kaken 2003-10p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44230/files/CA-PR-MUKAIDA-N-kaken 2003-10p.pdf"},"version_id":"bf917429-76a9-402f-9782-0d561384305a"}]},"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":"肝障害の遷延化に関与する因子の検索に基づく、慢性肝障害の新規の早期診断法の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"肝障害の遷延化に関与する因子の検索に基づく、慢性肝障害の新規の早期診断法の開発"},{"subitem_title":"Development of a novel diagnostic method for early detection of chronic liver diseases through the molecular pathological analysis of chronic liver disease models","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2831"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-04-20"},"publish_date":"2018-04-20","publish_status":"0","recid":"44230","relation_version_is_last":true,"title":["肝障害の遷延化に関与する因子の検索に基づく、慢性肝障害の新規の早期診断法の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:41:04.729729+00:00"}