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Development of an animal model of the vanishing bile duct syndrome

Research Project

Project/Area Number 19590773
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKochi University

Principal Investigator

ONISHI Saburou  Kochi University, 教育研究部・医療学系, 教授 (60136380)

Co-Investigator(Kenkyū-buntansha) SAIBARA Toshiji  高知大学, 教育研究部・医療学系, 准教授 (60145125)
TAKAHASHI Masaya  高知大学, 教育研究部・医療学系, 助教 (80380335)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords胆管炎 / TRAIL / 自己免疫 / 胆汁性肝硬変 / 胆管障害 / TRAILレセプター / death domain / 遺伝子多型 / bile duct / death receptor / apoptosis / autoimmune / mouse
Research Abstract

TRAILレセプターのdeath domainに対する単クローン性抗体は、腫瘍細胞特異的な細胞性免疫を惹起して、腫瘍細胞の排除を行う。しかし、副作用として時に胆管上皮細胞障害を誘発し慢性胆管炎に移行する。同様の免疫応答による慢性胆管肝炎はvanishing bile duct症候群として知られ、移植肝の急性および慢性拒絶反応の表現型である。TRAILレセプターのdeath domainにアミノ酸置換を伴う遺伝子多型がマウス存在することを見いだしたので、この抗原決定基に対する免疫応答が難治性の慢性胆管肝炎vanishing bile duct症候群を惹起する可能性があると考え、RT-PCRを用いて各種マウスstrainのTRAILレセプターのdeath domainにつき、遺伝子配列を決定した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (50 results)

All 2009 2008 2007

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (18 results) Book (18 results)

  • [Journal Article] Preserved tissue-structure of efferent ductules in aromatase deficient mice2008

    • Author(s)
      Toda K, Okada T, Hayashi Y, Saibara T.
    • Journal Title

      J Endocrinol 199

      Pages: 137-146

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients2008

    • Author(s)
      Enya M, Horikawa Y, Kuroda E, Yonemaru K, Tonooka N, Tomura H, Oda N, Yokoi N, Yamagata K, Shihara N, Iizuka K, Saibara T, Seino S, Takeda J
    • Journal Title

      Human Mutat 29

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of fascin-1, an actin-bundling protein, in migrating hepatoblasts during rat liver development.2008

    • Author(s)
      Hayashi Y, Toda K, Saibara T, Okamoto S, Osanai M, Enzan H, Lee GH.
    • Journal Title

      Cell Tissue Res. 334

      Pages: 219-226

    • NAID

      120000797468

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preserved tissue-strueture of efferent duetules in aromatase deficient mice.2008

    • Author(s)
      Toda K, Okada T, Hayashi Y, Saibara T.
    • Journal Title

      J. Endocrinol 199

      Pages: 137-146

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients.2008

    • Author(s)
      Enya M, Horikawa Y, Kurod a E, Yonemaru K, et al.
    • Journal Title

      Human Mutat 29

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of fascin-1, an actin-bundling protein, in migrating hepatoblasts during rat liver development.2008

    • Author(s)
      Hayashi Y, Toda K, Saibara T, Okamoto S, et al.
    • Journal Title

      Cell Tissue Res 334

      Pages: 219-226

    • NAID

      120000797468

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The phosphatidyl ethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population2007

    • Author(s)
      Dong H, Wang J, Li C, Hirose A, Nozaki Y, Takahashi M, Ono M, Akisawa N, Iwasaki S, Saibara T, Onishi S.
    • Journal Title

      J Hepatol 46

      Pages: 915-920

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome2007

    • Author(s)
      Kono M, Tatsumi K, Saibara T, Nakamura A, Tanabe N, Takiguchi Y, Kuriyama T.
    • Journal Title

      Chest 131

      Pages: 1387-1392

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis2007

    • Author(s)
      Hirose A, Ono M, Saibara T, Nozaki Y, Masuda K, Yoshioka A, Takahashi M, Akisawa N, Iwasaki S, Oben JA, Onishi S.
    • Journal Title

      Hepatology 45

      Pages: 1375-81

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Decreased lipoprotein lipase in obstructive sleep apnea syndrome2007

    • Author(s)
      Iesato K, Tatsumi K, Saibara T, Nakamura A, Terada J, Tada Y, Sakao S, Tanabe N, Takiguchi Y, Kuriyama T.
    • Journal Title

      Circ J 71

      Pages: 1293-1298

    • NAID

      110006368859

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fibrate for treatment of primary biliary cirrhosis2007

    • Author(s)
      Iwasaki S, Akisawa N, Saibara T, Onishi S.
    • Journal Title

      Hepatol Res 37 (Suppl 3)

    • NAID

      10019797596

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The phosphatidylethanolamine N-methyl- transferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population2007

    • Author(s)
      Dong H, Wang J, Li C, et. al.
    • Journal Title

      J Hepatol 45

      Pages: 915-920

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis2007

    • Author(s)
      Hirose A, Ono M, Saibara T, et. al.
    • Journal Title

      Hepatology 45

      Pages: 1375-1381

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fibrate for treatment of primary biliary cirrhosis2007

    • Author(s)
      Iwasaki S, Akisawa N, Saibara T, et. al.
    • Journal Title

      Hepatol Res 37

    • NAID

      10019797596

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Secondary extrahepatic portal obstruetion resulted from thrombus in splenic vein aneurysma.2008

    • Author(s)
      Kuratani Y, Ichikawa H, Hirose A, Nozaki Y, et al.
    • Organizer
      7^<th> Japan Society of Hepatology Single Topic Conference
    • Place of Presentation
      Fukuoka, Japan Acros Fukuoka
    • Year and Date
      2008-11-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Secondary extrahepatic portal obstruction resulted from thrombus in splenic vein aneurysma2008

    • Author(s)
      Kuratani Y, Ichikawa H, Hirose A, Nozaki Y, Takahashi M, Iwasaki S, Saibara T, Onishi S.
    • Organizer
      7^<th> Japan Society of Hepatology Single Topic Conference
    • Place of Presentation
      Fukuoka
    • Year and Date
      2008-09-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Angiotensin II type 1 receptor blocker attenuates the progression of nonalcoholic steatohepatitis (NASH)2008

    • Author(s)
      Hirose A, Ono M, Saibara T, Nozaki Y, Takahashi M, Iwasaki S, Oben JA, Onishi S.
    • Organizer
      European Association for the Study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-24
    • Related Report
      2008 Final Research Report
  • [Presentation] Super-paramagnetic iron oxide-MRI : A novel technique in experimental liver studies shows defective Kupffer cell phagocytic function in human non alcoholic fatty liver disease2008

    • Author(s)
      Ono M, Kubota K, Hirose A, Nozaki Y, Takahashi M, Iwasaki S, Saibara T, Ogawa Y, Onishi S, Oben JA
    • Organizer
      European Association for the Study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-24
    • Related Report
      2008 Final Research Report
  • [Presentation] Methionine-choline metabolism is involved in the pathogenesis of nonalcoholic steatohepatitis2008

    • Author(s)
      Tokumitsu K, Ogasawara K, Maki M, Hirose A, Nozaki Y, Takahashi M, Ono M, Iwasaki S, Saibara T, Onishi S.
    • Organizer
      European Association for the Study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-24
    • Related Report
      2008 Final Research Report
  • [Presentation] Angiotensin II type 1 receptor blocker attenuates the progression of nonalcoholic steatohepatitis (NASH).2008

    • Author(s)
      Hirose A, Ono M, Saibara T, Nozaki Y, et al.
    • Organizer
      European Association for the study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Super-paramagnetic iron oxide-MRI : A novel technique in experi mental liver studies shows defective Kupffer cell phagocytic function in human non alcoholic fatty liver disease.2008

    • Author(s)
      Ono M, Kubota K, Hirose A, Nozaki Y, Takahashi M, et al.
    • Organizer
      European Association for the study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Methionine-choline metabolism is involved in the pathogenesis of nonalcoholic steatohepatitis.2008

    • Author(s)
      Tokumitsu K, Ogasawara K, Maki M, Hirose A, et al.
    • Organizer
      European Association for the study of Liver Disease
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-04-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] The Cog2 gene A2217G single nucleotide polymorphism confers susceptibility to hepatocyte ballooning in NASH patients2007

    • Author(s)
      Saibara T, Yoshioka A, Hirose A, Nozaki Y, Takahashi M, Ono M, Iwasaki S, Onishi S
    • Organizer
      Asia Pacific digestive week 2007
    • Place of Presentation
      Kobe
    • Year and Date
      2007-10-16
    • Related Report
      2008 Final Research Report
  • [Presentation] The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population2007

    • Author(s)
      Saibara T, Yoshioka A, Hirose A, Nozaki Y, Takahashi M, Ono M, Iwasaki S, Onishi S
    • Organizer
      Asia Pacific digestive week 2007
    • Place of Presentation
      Kobe
    • Year and Date
      2007-10-16
    • Related Report
      2008 Final Research Report
  • [Presentation] Nonalcoholic fatty liver disease is a hepatic manifestation of metabolic syndrome2007

    • Author(s)
      T.Saibara
    • Organizer
      International symposium "Oxidative Stress Summit"
    • Place of Presentation
      Osaka
    • Year and Date
      2007-07-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] Metabolic syndrome as the pathogenic background for the development of NASH2007

    • Author(s)
      Saibara T, Ono M, Hirose A, Onishi S
    • Organizer
      17^<th> Asia-Pacific Association for the Study of Liver Disease
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-03-30
    • Related Report
      2008 Final Research Report
  • [Presentation] Angiotensin II type 1 receptor blocker inhibits fibrosis in rats steatohepatitis2007

    • Author(s)
      Ono M, Hirose A, Saibara T, Nozaki Y, Masuda K, Yoshioka A, Takahashi M, Akisawa N, Iwasaki S, Onishi S
    • Organizer
      17^<th> Asia-Pacific Association for the Study of Liver Disease
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-03-30
    • Related Report
      2008 Final Research Report
  • [Presentation] Metabolic syndrome as the pathogenic background for the development of NASH2007

    • Author(s)
      T.Saibara, M.Ono, A.Hirose, et. al.
    • Organizer
      17th Asia-Pasific Association for the Study of Liver Disease
    • Place of Presentation
      Kyoto
    • Related Report
      2007 Annual Research Report
  • [Presentation] Angiotensin II type 1 receptor blocker inhibits fibrosis in rats steatohepatitis2007

    • Author(s)
      M.Ono, A.Hirose, T.Saibara, et. al.
    • Organizer
      17th Asia-Pasific Association for the Study of Liver Disease
    • Place of Presentation
      Kyoto
    • Related Report
      2007 Annual Research Report
  • [Presentation] Possibie involvement of impaired choline-methionine metabolism in the pathogenesis of nonalcoholic fatty liver disease2007

    • Author(s)
      T.Saibara, M.Ono, S.Onishi
    • Organizer
      Asia Pasific digestive week 2007
    • Place of Presentation
      Kobe
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Cog2 gene A2217G single nucleotide polymorphism confers susceptibility to hepatocyte ballooning in NASH patients2007

    • Author(s)
      T.Saibara, A.Yoshioka, A.Hirose, et. al.
    • Organizer
      Asia Pasific digestive week 2007
    • Place of Presentation
      Kobe
    • Related Report
      2007 Annual Research Report
  • [Presentation] The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population2007

    • Author(s)
      T.Saibara, A.Yoshioka, A.Hirose, et. al.
    • Organizer
      Asia Pasific digestive week 2007
    • Place of Presentation
      Kobe
    • Related Report
      2007 Annual Research Report
  • [Book] C型肝炎のベスト治療2009

    • Author(s)
      西原利治
    • Publisher
      医学書院
    • Related Report
      2008 Final Research Report
  • [Book] 2009今日の治療指針2009

    • Author(s)
      西原利治
    • Publisher
      医学書院
    • Related Report
      2008 Final Research Report
  • [Book] Annual Review 消化器 20092009

    • Author(s)
      西原利治
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] 消化器疾患最新の治療2009

    • Author(s)
      西原利治
    • Publisher
      南江堂
    • Related Report
      2008 Final Research Report
  • [Book] 病気と薬パーフェクトBOOK2008

    • Author(s)
      西原利治、小野正文
    • Publisher
      南山堂
    • Related Report
      2008 Final Research Report
  • [Book] 第94回日本消化器病学会総会ポストグラジュエイトコース2008

    • Author(s)
      西原利治
    • Publisher
      日本消化器病学会
    • Related Report
      2008 Final Research Report
  • [Book] 酸化ストレスと肝疾患2008

    • Author(s)
      杜井峰、小笠原光成、植瑞希、廣瀬享、野崎靖子、小野正文、岩崎信二、西原利治、大西三朗
    • Publisher
      メディカルジャーナル社
    • Related Report
      2008 Final Research Report
  • [Book] 肝疾患レジデントマニュアル2008

    • Author(s)
      西原利治
    • Publisher
      医学書院
    • Related Report
      2008 Final Research Report
  • [Book] キーワードでわかるメタボリックシンドローム2008

    • Author(s)
      西原利治、小野正文
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] NASH診療best approach2008

    • Author(s)
      西原利治
    • Total Pages
      264
    • Publisher
      中外医学社
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Book] NASH診療ハンドブック2007

    • Author(s)
      西原利治
    • Total Pages
      165
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] Annual Review消化器20072007

    • Author(s)
      西原利治
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] 薬剤師のための臨床講座2007

    • Author(s)
      西原利治
    • Publisher
      メジテース
    • Related Report
      2008 Final Research Report
  • [Book] Dataで読み解く内科疾患2007

    • Author(s)
      西原利治
    • Publisher
      永井書店
    • Related Report
      2008 Final Research Report
  • [Book] 肝臓病の最新治療2007

    • Author(s)
      西原利治、小野正文、大西三朗
    • Publisher
      先端医療技術研究所
    • Related Report
      2008 Final Research Report
  • [Book] アルコールと医学生物学2007

    • Author(s)
      李春媚、小笠原光成、植瑞希、廣瀬享、野崎靖子、高橋昌也、小野正文、岩崎信二、西原利治、大西三朗
    • Publisher
      東洋書店
    • Related Report
      2008 Final Research Report
  • [Book] 肝硬変のマネジメント2007

    • Author(s)
      西原利治、小野正文、大西三朗
    • Publisher
      医薬ジャーナル社
    • Related Report
      2008 Final Research Report
  • [Book] わかりやすい内科学2007

    • Author(s)
      西原利治、大西三朗
    • Publisher
      文光堂
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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