Development of an animal model of the vanishing bile duct syndrome

• Project/Area Number: 19590773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kochi 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: ¥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。

Research Products

• [Journal Article] Preserved tissue-structure of efferent ductules in aromatase deficient mice (2008)
  • Author(s): Toda K, Okada T, Hayashi Y, Saibara T.
  • Journal Title: J Endocrinol 199 Pages: 137-146
  • 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, 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] The phosphatidyl ethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population (2007)
  • 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
  • Peer Reviewed
• [Journal Article] Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome (2007)
  • Author(s): Kono M, Tatsumi K, Saibara T, Nakamura A, Tanabe N, Takiguchi Y, Kuriyama T.
  • Journal Title: Chest 131 Pages: 1387-1392
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis (2007)
  • 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
  • Peer Reviewed
• [Journal Article] Decreased lipoprotein lipase in obstructive sleep apnea syndrome (2007)
  • 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
  • Peer Reviewed
• [Journal Article] Fibrate for treatment of primary biliary cirrhosis (2007)
  • Author(s): Iwasaki S, Akisawa N, Saibara T, Onishi S.
  • Journal Title: Hepatol Res 37 (Suppl 3)
  • NAID: 10019797596
  • Peer Reviewed
• [Journal Article] The phosphatidylethanolamine N-methyl- transferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population (2007)
  • Author(s): Dong H, Wang J, Li C, et. al.
  • Journal Title: J Hepatol 45 Pages: 915-920
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis (2007)
  • Author(s): Hirose A, Ono M, Saibara T, et. al.
  • Journal Title: Hepatology 45 Pages: 1375-1381
  • Peer Reviewed
• [Journal Article] Fibrate for treatment of primary biliary cirrhosis (2007)
  • Author(s): Iwasaki S, Akisawa N, Saibara T, et. al.
  • Journal Title: Hepatol Res 37
  • NAID: 10019797596
  • 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
• [Presentation] Secondary extrahepatic portal obstruction resulted from thrombus in splenic vein aneurysma (2008)
  • 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
• [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
• [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 disease (2008)
  • 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
• [Presentation] Methionine-choline metabolism is involved in the pathogenesis of nonalcoholic steatohepatitis (2008)
  • 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
• [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
• [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
• [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
• [Presentation] The Cog2 gene A2217G single nucleotide polymorphism confers susceptibility to hepatocyte ballooning in NASH patients (2007)
  • 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
• [Presentation] The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population (2007)
  • 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
• [Presentation] Nonalcoholic fatty liver disease is a hepatic manifestation of metabolic syndrome (2007)
  • Author(s): T.Saibara
  • Organizer: International symposium "Oxidative Stress Summit"
  • Place of Presentation: Osaka
  • Year and Date: 2007-07-14
• [Presentation] Metabolic syndrome as the pathogenic background for the development of NASH (2007)
  • 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
• [Presentation] Angiotensin II type 1 receptor blocker inhibits fibrosis in rats steatohepatitis (2007)
  • 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
• [Presentation] Metabolic syndrome as the pathogenic background for the development of NASH (2007)
  • 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
• [Presentation] Angiotensin II type 1 receptor blocker inhibits fibrosis in rats steatohepatitis (2007)
  • 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
• [Presentation] Possibie involvement of impaired choline-methionine metabolism in the pathogenesis of nonalcoholic fatty liver disease (2007)
  • Author(s): T.Saibara, M.Ono, S.Onishi
  • Organizer: Asia Pasific digestive week 2007
  • Place of Presentation: Kobe
• [Presentation] The Cog2 gene A2217G single nucleotide polymorphism confers susceptibility to hepatocyte ballooning in NASH patients (2007)
  • Author(s): T.Saibara, A.Yoshioka, A.Hirose, et. al.
  • Organizer: Asia Pasific digestive week 2007
  • Place of Presentation: Kobe
• [Presentation] The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population (2007)
  • Author(s): T.Saibara, A.Yoshioka, A.Hirose, et. al.
  • Organizer: Asia Pasific digestive week 2007
  • Place of Presentation: Kobe
• [Book] C型肝炎のベスト治療 (2009)
  • Author(s): 西原利治
  • Publisher: 医学書院
• [Book] 2009今日の治療指針 (2009)
  • Author(s): 西原利治
  • Publisher: 医学書院
• [Book] Annual Review 消化器 2009 (2009)
  • Author(s): 西原利治
  • Publisher: 中外医学社
• [Book] 消化器疾患最新の治療 (2009)
  • Author(s): 西原利治
  • Publisher: 南江堂
• [Book] 病気と薬パーフェクトBOOK (2008)
  • Author(s): 西原利治、小野正文
  • Publisher: 南山堂
• [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
• [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
• [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
• [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
• [Book] NASH診療best approach (2008)
  • Author(s): 西原利治
  • Total Pages: 264
  • Publisher: 中外医学社
• [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
• [Book] Annual Review消化器2007 (2007)
  • Author(s): 西原利治
  • Publisher: 中外医学社
• [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
• [Book] Dataで読み解く内科疾患 (2007)
  • Author(s): 西原利治
  • Publisher: 永井書店
• [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
• [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
• [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
• [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