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2005 Fiscal Year Final Research Report Summary

Elucidation of pathophysiology for various digestive diseases

Research Project

Project/Area Number 15209024
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

CHIBA Tsutomu  Kyoto University, Department of Gastroenterology & Hepatology, Professor, 医学研究科, 教授 (30188487)

Co-Investigator(Kenkyū-buntansha) OKAZAKI Kazuichi  Kansai Medical University, 3^<rd> Department of Internal Medicine, Professor, 医学部, 教授 (70145126)
NISHIO Akiyoshi  Kyoto University, Department of Gastroenterology & Hepatology, Assistant Professor, 医学研究科, 助教授 (50362463)
Project Period (FY) 2003 – 2005
KeywordsH.pylori / Gastritis / MALT lymphoma / Th1 / Th2 response / Autoimmune pancreatitis / Inflammatory bowel disease / Mycobacterium patratuberculosis / basic FGF
Research Abstract

In this study, we tried to elucidate pathophysiology of H.pylori-induced gastyritis, autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) all of which involve immunological responses, and the following results were obtained. (1)In human, patients with gastric ulcer had Th1-predominant immunological response, whereas patients with duodenal ulcer were more polarized to Th2 response. Moreover, in patients with MALT lymphoma, Th2 reaction was remarkable. (2)In mice, severe gastritis developed by HP infection in C57black mice, a typical Th1-type strain, whereas no gastritis could be observed in Balb/c mice, a typical Th2-type strain. On the other hand, by thymectomy, severe gastritis seen in C57black mice disappeared and MALT lymphoma developed in Balb/c mice. Moreover, for MALT lymphoma B cell growth in vitro, in addition to HP presence of HP specific T cells and peripheral blood DC were essential. (3)By using serum of the patient who was negative for anti CAII antibody or anti-lactoferin but with high serum IgG titer, we identified pancreatic trypsin inhibitor as a candidate target for autoantibody in patients with autoimmune pancreatitis. (4)In patients with IBD, serum titiers for anti-Mycobacterium antibody was significantly higher than normal subjects, and involvement of Mycobacterium paratuberculosis infection in pathophysiology of human IBD was suggested. (5)Moreover, involvement of CMV as well as EBV infection in the pathophysiology of IBD was also suggested, and importance of measurement of and comparison of copy numbers of CMV gene in both affected and non-affected colonic site for diagnosis of CMV infection in patients with IBD was indicated. (6)For development of IBD, abnormality of permeability of epithelial barrier and that of regeneration of the epithelium were found to be involved. Accordingly, administration of growth factors such as bFGF, that enhances repair of epithelial cells appeared to be effective for the treatment of IBD.

  • Research Products

    (26 results)

All 2006 2005 2004 2003

All Journal Article (26 results)

  • [Journal Article] STAT3 activation is involved in nuclear accumulation of b-catenin in colorectal cancer.2006

    • Author(s)
      Kawada M, Seno H, Chiba T, et al.
    • Journal Title

      Cancer Res 66

      Pages: 2913-2917

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gastric mucosal hyperplasia via up-regulation of gastrin induced by persistent activation of gastric innate immunity in MHC class II-deficient mice.2006

    • Author(s)
      Fukui H, Nishio A, Chiba T, et al.
    • Journal Title

      Gut 55

      Pages: 607-615

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.2006

    • Author(s)
      Nakase H, Nishio A, Chiba T, et al.
    • Journal Title

      Inflamm Bowel Dis 12

      Pages: 62-69

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Signal transducers and activators of transcription 3 activation is involved in nuclear accumulation of beta-catenin in colorectal cancer.2006

    • Author(s)
      Kawada M, Seno H, Uenoyama Y, Sawabu T, Kanda N, Fukui H, Shimahara Y, Chiba T
    • Journal Title

      Cancer Res. 66

      Pages: 2913-2917

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice.2006

    • Author(s)
      Fukui T, Nishio A, Okazaki K, Uza N, Ueno S, Kido M, Inoue S, Kitamura H, Kiriya K, Ohashi S, Asada M, Tamaki H, Matsuura M, Kawasaki K, Suzuki K, Uchida K, Fukui H, Nakase H, Watanabe N, Chiba T
    • Journal Title

      Gut. 55

      Pages: 607-615

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.2006

    • Author(s)
      Nakase H, Nishio A, Tamaki H, Matsuura M, Asada M, Chiba T. Okazaki K
    • Journal Title

      Inflamm Bowel Dis. 12

      Pages: 62-69

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible role of REG Iα protein in ulcerative colitis and colitic cancer.2005

    • Author(s)
      Sekikawa A, Fukui H, Chiba T, et al.
    • Journal Title

      Gut 54

      Pages: 1437-1444

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Distinct gastric mucosal T cell responses to H.pylori infection : Th1 and Th2, may result in different clinical outcomes : gastric ulcer and duodenal ulcer.2005

    • Author(s)
      Itoh T, Seno H, Chiba T, et al.
    • Journal Title

      Scand J Gastroenterol 40

      Pages: 641-647

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.2005

    • Author(s)
      Matsuura M, Nakase H, Chiba T, et al.
    • Journal Title

      Gastroenterology 128

      Pages: 975-986

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Th response to Helicobacter pylori differs between patients with gastric ulcer and duodenal ulcer.2005

    • Author(s)
      Itoh T, Seno H, Kita T, Chiba T. Wakatsuki Y
    • Journal Title

      Scand J Gastroenterol 40

      Pages: 641-647

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible role of REG Ia protein in ulcerative colitis and colitic cancer.2005

    • Author(s)
      Sekikawa A, Fukui H, Fujii S, Nanakin A, Kanda N, Uenoyama Y, Sawabu T, Hisatsune H, Kusaka T, Ueno S, Nakase H, Seno H, Fujimori T, Chiba T
    • Journal Title

      Gut 54

      Pages: 1437-1444

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.2005

    • Author(s)
      Matsuura M, Okazaki K, Nishio A, Nakase H, Tamaki H, Uchida K, Nishi T, Asada M, Kawasaki K, Fukui T, Yoshizawa H, Ohashi S, Inoue S, Kawanami C, Hiai H, Tabata Y, Chiba T
    • Journal Title

      Gastroenterology 128

      Pages: 975-986

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] REG Ia protein may function as a trophic and/or anti-apoptitic factor in the development of gastric cancer.2005

    • Author(s)
      Sekikawa A, Fukui H, Fujii S, Takeda J, Nanakin A, Hisatsune H, Seno H, Takasawa S, Okamoto H, Fujimori T, Chiba T
    • Journal Title

      Gastroenterology 128

      Pages: 642-653

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner.2004

    • Author(s)
      Iwai A, Marusawa H, Matsuzawa S, Fukushima T, Hijikata M, Reed JC, Shimotohno K, Chiba T
    • Journal Title

      Oncogene 23

      Pages: 7593-7600

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells.2004

    • Author(s)
      Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, Sekikawa A, Kawada M, Suzuki K, Kayahara T, Fukui H, Sawada M, Chiba T
    • Journal Title

      Oncogene 23

      Pages: 4921-4929

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of colonic neoplasia in p53 deficient mice with experimental colitis induced by dextran sulfate sodium.2004

    • Author(s)
      Fujii S, Fujimori T, Kawamata H, Takada J, Kitajima K, Omotehara F, Kaihara T, Kusaka T, Ichikawa K, Ohkura Y, Ono Y, Imura J, Yamaoka S, Sakamoto C, Ueda Y, Chiba T
    • Journal Title

      Gut 53

      Pages: 710-716

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immuno-genetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice.2004

    • Author(s)
      Fukui T, Okazaki K, Tamaki H, Kawasaki K, Matsuura M, Asada M, Nishi T, Uchida K, Iwano M, Ohana M, Hiai H, Chiba T
    • Journal Title

      Lab Invest 84

      Pages: 485-492

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A coordinated cytotoxic effect of IFN-γ and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis.2003

    • Author(s)
      Itoh T, Yoshida M, Chiba T, et al.
    • Journal Title

      Helicobacter 8

      Pages: 268-278

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prevention of the development of autoimmune gastritis by Helicobacter pylori infectgion in neonatal thymectomised mice.2003

    • Author(s)
      Ohana M, Okazaki K, Chiba T, et al.
    • Journal Title

      Gut 52

      Pages: 1102-1110

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy.2003

    • Author(s)
      Nishi T, Okazaki K, Chiba T, et al.
    • Journal Title

      Infect Immun 71

      Pages: 2153-2162

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Elimination of local macrophages in the intestine prevents chronic colitis in interleukin-10 deficient mice.2003

    • Author(s)
      Watanabe N, Ikuta K, Chiba T, et al.
    • Journal Title

      Dig Dis Sci 48

      Pages: 408-414

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in mongolian gerbils.2003

    • Author(s)
      Fukui H, Franceschi F, Penland RL, Sakai T, Sepulveda AR, Fujimori T, Terano A, Chiba T, Genta RM
    • Journal Title

      Lab Invest 83

      Pages: 1777-1786

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A coordinated cytotoxic effect of IFN-γ and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis.2003

    • Author(s)
      Itoh T, Yoshida M, Chiba T, Kita T, Wakatsuki Y
    • Journal Title

      Helicobacter 8

      Pages: 268-278

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis.2003

    • Author(s)
      Ohana M, Okazaki K, Oshima C, Kawasaki K, Fukui T, Tamaki H, Matsuura M, Asada M, Nishi T, Uchida K, Uose S, Nakase H, Iwano M, Matsushima Y, Hiai H, Chiba T
    • Journal Title

      Gut 52

      Pages: 1102-1110

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected neonatal thymectomized BALB/c mice.2003

    • Author(s)
      Nishi T, Okazaki K, Kawasaki K, Fukui T, Tamaki H, Matsuura M, Asada M, Watanabe T, Uchia K, Watanabe N, Nakase H, Ohana M, Hiai H, Chiba T
    • Journal Title

      Infect Immun 71

      Pages: 2153-2162

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice.2003

    • Author(s)
      Watanabe N, Ikuta K, Okazaki K, Nakase H, Tabata Y, Matsuura M, Tamaki H, Kawanami C, Honjo T, Chiba T
    • Journal Title

      Dig Dis Sci. 48

      Pages: 408-414

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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