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    Authors: Nakanuma, Yasuni;

    We demonstrated the participation of innate immunity in the pathophysiology of biliary tract by using human materials of hepatobiliary tissues and cultured human biliary epithleial cells. The following three data were obtained. (1) Biliary epithelial cells expressed Toll-like receptor (TLR), and they responded to pathogen associated molecular patterns (PAMPs) as a physiological response of innate immunity. This reaction seemed to be involved physiologically in biliary homeostasis against bacterial components contained in bile. By cultural study, it was found that endotoxin tolerance of TLF4 was induced by two step processes, and that IRAK-M is also involved in this process by a negative regulator. (2) It is reported that biliary atresia could be caused by infection of double strand RNA virus. It was found in this study that biliary epithelial cells express TLR3 reacting with double strand RNA, and NF-B and IFN-β is incuded in these cells by exposing to the ligands of TLR3. In addition, TRAIL, a proapoptotic molecule was also induced in this process. In the affected bile ducts of biliary atresia, TLR3 and TRAIL were expressed in biliary epithelial cells. These findings suggested that virus, particularly double strand RNA virus was likely involved in the pathogenesis of biliary atresia, particularly the apoptotic loss of infected biliary epithelial cells. (3) Primary biliary cirrhosis is an autoimmune liver disease and biliary epithelial cells underwent apoptosis, probably resulting from bacterial infection. By examing the apoptotic mechanisms of biliary epithelial cells and innate immunity, it was found that biliary epithelial cells under protein-recessive state, underwent apoptosis by PAMPs stimulation, and HIAP-1 overexpression was important in antiapoptotic effect of biliary epithelial cells due to PAMPs. These studies showed that innate immunity, especially TLR, is involved in the pathophysiology of the biliary tree. 胆管系疾患の病態形成における自然免疫の関与を、人体材料およびヒト培養胆管細胞を用い、以下の結果を得た。 (1)胆管系自然免疫トレランスの解析:胆管細胞はTLRを発現し、細菌菌体成分などのPAMPs刺激に対して自然免疫応答を示すが、生理的状態では常在菌体成分に対するトレランスが胆道系ホメオスターシスの維持に重要である。培養胆管細胞を用いた検討にて、TLR4リガンドであるLPSの2段階刺激でエンドトキシントレランスが誘導されることを明らかにし、更にTLR細胞内シグナルの負の制御因子であるIRAK-Mがトレランス誘導に関与していることも明らかにした。 (2)胆道閉鎖症におけるレオウイルス科ウイルスの関与:胆道閉鎖症の原因として二本鎖RNAウイルスであるレオウイルス科ウイルスの感染が推測されている。胆管細胞は二本鎖RNAの認識受容体であるTLR3を発現し、リガンド刺激にてNF-κB活性化およびIFN-β1産生の誘導とアポトーシス誘導分子であるTRAILの発現亢進がみられた。また胆道閉鎖症の肝外胆管ではTLR3とTRAILを発現し、またNF-κBの活性化が証明された。ウイルス感染が胆道閉鎖症の胆管消失に直接関与していることが示唆された。 (3)胆道系自然免疫と胆管細胞アポトーシスの解析:原発性胆汁性肝硬変(PBC)は胆管細胞アポトーシスによる胆管消失を特徴とする自己免疫疾患で、病因として細菌感染症の関与が想定されている。胆管細胞アポトーシスの分子基盤および自然免疫の関与について解析した結果、胆管細胞は蛋白合成抑制状態ではPAMPs刺激にて直接アポトーシスが誘導されることを示し、さらにPAMPsに対する抗アポトーシス効果の一つとしてNF-κB依存性のHIAP-1発現亢進が重要であることを示した。 出典:「胆管粘膜でのToll-like receptorの発現とその制御異常」研究成果報告書 課題番号15390114 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) 本文データは著者版報告書より作成 研究課題/領域番号:15390114, 研究期間(年度):2003–2006

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    JAIRO
    2007
    Data sources: JAIRO
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    日本銀行金融研究所所蔵藩札等 資料番号:ⅢAイコc2-31-6 科学研究費助成事業(研究成果公開促進費)で電子化を実施 データベースの名称:藩札等に関する統合データベース 課題番号:21HP8029 利用に関するお問い合わせ: 画像の転載(出版物・HP等)に際しては、日本銀行貨幣博物館への申請手続きが必要です。 詳しくは貨幣博物館ホームページ(http://www.imes.boj.or.jp/cm/service/)をご覧ください。

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      JAIRO
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  • Authors: 酒井 一博/堀野 定雄/G.W.クロックフォード/近藤 充輔/山室 栄三/伊藤 昭好/毛利 哲夫/佐々木 司/野村  茂/斉藤 良夫/坂野 純子/李 卿/野沢 浩/宮北 隆志/森 和夫/辻村 昌昭/木村 菊二/齊藤 太/槇塚 忠穂/松田 義雄/西口 宏美/野沢 浩/;
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    Authors: Japan. Ministry of Finance;

    【対象期間】 自大正2年至同4年【計数出所】 大日本外国貿易年表、大日本外国貿易月表 official statistics: aggregate data 公的統計: 集計データ、統計表 Aggregation Object 対象 集計

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    JAIRO
    2022
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      JAIRO
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    JAIRO
    2022
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      JAIRO
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    JAIRO
    2004
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      JAIRO
      2004
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    博士学位論文の要旨及び審査結果の要旨 (Summary of Thesis(DR)) application/pdf 184468 bytes

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    JAIRO
    1974
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      JAIRO
      1974
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768,725 Research products
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    Authors: Nakanuma, Yasuni;

    We demonstrated the participation of innate immunity in the pathophysiology of biliary tract by using human materials of hepatobiliary tissues and cultured human biliary epithleial cells. The following three data were obtained. (1) Biliary epithelial cells expressed Toll-like receptor (TLR), and they responded to pathogen associated molecular patterns (PAMPs) as a physiological response of innate immunity. This reaction seemed to be involved physiologically in biliary homeostasis against bacterial components contained in bile. By cultural study, it was found that endotoxin tolerance of TLF4 was induced by two step processes, and that IRAK-M is also involved in this process by a negative regulator. (2) It is reported that biliary atresia could be caused by infection of double strand RNA virus. It was found in this study that biliary epithelial cells express TLR3 reacting with double strand RNA, and NF-B and IFN-β is incuded in these cells by exposing to the ligands of TLR3. In addition, TRAIL, a proapoptotic molecule was also induced in this process. In the affected bile ducts of biliary atresia, TLR3 and TRAIL were expressed in biliary epithelial cells. These findings suggested that virus, particularly double strand RNA virus was likely involved in the pathogenesis of biliary atresia, particularly the apoptotic loss of infected biliary epithelial cells. (3) Primary biliary cirrhosis is an autoimmune liver disease and biliary epithelial cells underwent apoptosis, probably resulting from bacterial infection. By examing the apoptotic mechanisms of biliary epithelial cells and innate immunity, it was found that biliary epithelial cells under protein-recessive state, underwent apoptosis by PAMPs stimulation, and HIAP-1 overexpression was important in antiapoptotic effect of biliary epithelial cells due to PAMPs. These studies showed that innate immunity, especially TLR, is involved in the pathophysiology of the biliary tree. 胆管系疾患の病態形成における自然免疫の関与を、人体材料およびヒト培養胆管細胞を用い、以下の結果を得た。 (1)胆管系自然免疫トレランスの解析:胆管細胞はTLRを発現し、細菌菌体成分などのPAMPs刺激に対して自然免疫応答を示すが、生理的状態では常在菌体成分に対するトレランスが胆道系ホメオスターシスの維持に重要である。培養胆管細胞を用いた検討にて、TLR4リガンドであるLPSの2段階刺激でエンドトキシントレランスが誘導されることを明らかにし、更にTLR細胞内シグナルの負の制御因子であるIRAK-Mがトレランス誘導に関与していることも明らかにした。 (2)胆道閉鎖症におけるレオウイルス科ウイルスの関与:胆道閉鎖症の原因として二本鎖RNAウイルスであるレオウイルス科ウイルスの感染が推測されている。胆管細胞は二本鎖RNAの認識受容体であるTLR3を発現し、リガンド刺激にてNF-κB活性化およびIFN-β1産生の誘導とアポトーシス誘導分子であるTRAILの発現亢進がみられた。また胆道閉鎖症の肝外胆管ではTLR3とTRAILを発現し、またNF-κBの活性化が証明された。ウイルス感染が胆道閉鎖症の胆管消失に直接関与していることが示唆された。 (3)胆道系自然免疫と胆管細胞アポトーシスの解析:原発性胆汁性肝硬変(PBC)は胆管細胞アポトーシスによる胆管消失を特徴とする自己免疫疾患で、病因として細菌感染症の関与が想定されている。胆管細胞アポトーシスの分子基盤および自然免疫の関与について解析した結果、胆管細胞は蛋白合成抑制状態ではPAMPs刺激にて直接アポトーシスが誘導されることを示し、さらにPAMPsに対する抗アポトーシス効果の一つとしてNF-κB依存性のHIAP-1発現亢進が重要であることを示した。 出典:「胆管粘膜でのToll-like receptorの発現とその制御異常」研究成果報告書 課題番号15390114 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) 本文データは著者版報告書より作成 研究課題/領域番号:15390114, 研究期間(年度):2003–2006

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    JAIRO
    2007
    Data sources: JAIRO
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      2007
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    日本銀行金融研究所所蔵藩札等 資料番号:ⅢAイコc2-31-6 科学研究費助成事業(研究成果公開促進費)で電子化を実施 データベースの名称:藩札等に関する統合データベース 課題番号:21HP8029 利用に関するお問い合わせ: 画像の転載(出版物・HP等)に際しては、日本銀行貨幣博物館への申請手続きが必要です。 詳しくは貨幣博物館ホームページ(http://www.imes.boj.or.jp/cm/service/)をご覧ください。

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  • Authors: 酒井 一博/堀野 定雄/G.W.クロックフォード/近藤 充輔/山室 栄三/伊藤 昭好/毛利 哲夫/佐々木 司/野村  茂/斉藤 良夫/坂野 純子/李 卿/野沢 浩/宮北 隆志/森 和夫/辻村 昌昭/木村 菊二/齊藤 太/槇塚 忠穂/松田 義雄/西口 宏美/野沢 浩/;
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    Authors: Japan. Ministry of Finance;

    【対象期間】 自大正2年至同4年【計数出所】 大日本外国貿易年表、大日本外国貿易月表 official statistics: aggregate data 公的統計: 集計データ、統計表 Aggregation Object 対象 集計

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    博士学位論文の要旨及び審査結果の要旨 (Summary of Thesis(DR)) application/pdf 184468 bytes

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