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Dissection of autoimmune response and establishment of diagnosis and treatment of primary biliary cirrhosis

Research Project

Project/Area Number15390238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionClinical Research Center National Hospital Organization (NHO) Nagasaki Medical Center

Principal Investigator

ISHIBASHI Hiromi  Clinical Research Center, Nagasaki Medical Center, 臨床研究センター, 臨床研究センター長 (80127969)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Minoru  Clinical Research Center, Nagasaki Medical Center, 臨床研究センター, 先端技術研究部長 (40217906)
MIGITA Kiyoshi  Clinical Research Center, Nagasaki Medical Center, 臨床研究センター, 病因解析研究部長 (60264214)
KOMORI Atsumasa  Clinical Research Center, Nagasaki Medical Center, 臨床研究センター, 再生医療研究部長 (50234901)
ITO Masahiro  Clinical Research Center, Nagasaki Medical Center, 臨床研究センター, 部長 (30184691)
SHIMODA Shinji  Kyushu University Graduate School of Medical Science, Medicine and Biosystemic Science, 大学院・病態修復内科学, 助手 (30279319)
藤岡 ひかる  独立行政法人国立病院機構長崎医療センター, 臨床研究センター, 形態研究部長 (00264226)
喜多 宏人  自治医科大学, 消化器内科学, 助手 (80294974)
Project Period (FY) 2003 – 2005
Project Status Completed(Fiscal Year 2005)
Budget Amount *help
¥14,700,000 (Direct Cost : ¥14,700,000)
Fiscal Year 2005 : ¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 2004 : ¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 2003 : ¥8,500,000 (Direct Cost : ¥8,500,000)
Keywordsprimary biliary cirrhosis / bile duct damage / biliary epithelial cells / innate immunity / Toll-like receptor (TLR) / anti-gp210 antibody / prediction of prognosis / anti-mitochondrial antibody / PPARα / ミトコンドリア抗原 / 抗原特異的T細胞 / 予後予測因子 / ミトコンドリア抗体 / 自己反応性T細胞 / CD8陽性T細胞 / 病因関連抗原
Research Abstract

The objective of this study is to dissect the mechanism of autoimmune response in primary biliary cirrhosis (PBC) in order to develop the new strategy for the treatment of PBC.
Fist, we established human T cell clones derived from PBC patients or healthy subjects which react to PDC-E2/OGDC-E2 peptides. Using these T cell clones, we found that T cells reactive to PDC-E2 peptide cross-react to peptides derived from nuclear pore antigens (gp210), supporting the hypothesis that molecular mimicry is operative in the development of PBC. We also found that T cells derived from PBC patients are costimulation-independent, while T cells derived from health subjects are costimulation-dependent. The costimulation-independent autoreactive T cells, which do not become anergic when they contact with biliary epithelial cells (BEC), might play the pathological role in the development of PBC.
Second, we studied the role of BEC in the regulation of autoimmune response using T cell clones reactive to PDC-E2 … More peptides and human biliary epithelial cells (HIBEC) in vitro. We found that HIBEC can strongly inhibit the function of autoreactive T cells by producing prostaglandin-E2. We also found that Toll-like receptors (TLRs) 2,3,4 and 9 are constitutively expressed in HIBEC and the stimulation of these TLRs by their ligands induced the secretion of IL-6, IL-8 and MCP-1 via NF-kB and MAPK pathway. The expression of TLR4 was increased on the biliary epithelial cells of interlobular bile ducts in PBC liver. TLR3-type I interferon pathway was also activated in PBC liver. These results indicate that innate immune response may play a role in the initiation and/or maintenance of autoimmune response in PBC.
Finally, we studied the serological markers that can predict the long-term outcome of PBC patients. We found that patients who are sustained positive for anti-gp210 antibodies are at high risk for the progression to end-stage hepatic failure. Although the mechanism of the production of anti-gp210 antibodies remains to be elucidated, this predictive autoantibody should be useful for the identification of PBC patients who require treatment and long-term follow-up. Less

Report

(4results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report

Research Products

(82results)

All 2006 2005 2004 2003 Other

All Journal Article Book Publications

  • [Journal Article] Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis.2006

    • Author(s)
      Nakamura M, Kondo H, Mori T, et al, Ishibashi H.
    • Journal Title

      Hepatology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Guidelines for therapy of the chronic inflammatory liver diseases.2006

    • Author(s)
      Ishibashi H, Shimoda S, Nakamura M, Gershwin ME
    • Journal Title

      Seminars in Liver Disease (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory.2006

    • Author(s)
      Shimoda S, Ishikawa F, Kamihira T, Ishibashi H, et al.
    • Journal Title

      Gastroenterology 131(2)

      Pages : 606-618

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways.2006

    • Author(s)
      Yokoyama T, Komori A, Nakamura M, Takii Y, et al., Ishibashi H.
    • Journal Title

      Liver International 26(4)

      Pages : 467-476

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunosuppressant FK506 inhibits matrix metalloproteinase-9 induction in TNF- alpha- stimulated human hepatic stellate cells.2006

    • Author(s)
      Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, et al., Ishibashi H.
    • Journal Title

      Life Sci. 78(21)

      Pages : 2510-2515

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IgA class antibodies to 2-oxo-acid dehydrogenase complex are not predictive markers of histopathological progression in primary biliary cirrhosis.2006

    • Author(s)
      Omagari K, Kadokawa Y, Ishibashi H, et al.
    • Journal Title

      Autoimmunity 39(2)

      Pages : 107-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis.2006

    • Author(s)
      Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, et al. Ishibashi H
    • Journal Title

      J Autoimmunity 26(2)

      Pages : 138-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] T cell immunity and graft-versus-host disease (GVHD).2006

    • Author(s)
      Ichiki Y, Bowlus CL, Shimoda S, Ishibashi H, et al.
    • Journal Title

      Autoimmun Rev. 5(1)

      Pages : 1-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways.2006

    • Author(s)
      Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira T, Shimoda S, Mori T, Fujiwara S, Koyabu M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H
    • Journal Title

      Liver Int. 26(4)

      Pages : 467-476

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis.2006

    • Author(s)
      Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, Shimizu-Yoshida Y, Koyabu M, Matsuyama M, Mori T, Kamihira T, Daikoku M, Migita K, Yatsuhashi H, Nozaki N, Shimoda S, Ishibashi H
    • Journal Title

      J.Autoimmunity 26(2)

      Pages : 138-145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunosuppressant FK506 inhibits matrix metalloproteinase-9 induction in TNF-alpha-stimulated human hepatic stellate cells.2006

    • Author(s)
      Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, Yokoyama T, Takii Y, Mori T, Yatsuhashi H, Eguchi K, Ishibashi H
    • Journal Title

      Life Sci. 78(21)

      Pages : 2510-2515

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The immune response to mitochondrial autoantigens.2006

    • Author(s)
      Ishibashi H, Shimoda S, Gershwin ME.
    • Journal Title

      Seminars in Liver Disease 25(3)

      Pages : 337-346

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis.2006

    • Author(s)
      Nakamura M, Takii Y, Ito M, Komori A, Ishibashi H, et al.
    • Journal Title

      Journal of Autoimmunity 26(2)

      Pages : 138-145

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immunosuppressant FK506 inhibits matrix metalloproteinase-9 induction in TNF-alpha-stimulated human hepatic stellate cells.2006

    • Author(s)
      Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, Ishibashi H, et al.
    • Journal Title

      Life Science

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Human intra-hepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kB and -MAPK signaling pathways.2006

    • Author(s)
      Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira et al.
    • Journal Title

      Liver International (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The immune response to mitochondrial autoantigens.2006

    • Author(s)
      Ishibashi H, et al.
    • Journal Title

      Seminars in Liver Disease 25(3)

      Pages : 337-346

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis.2005

    • Author(s)
      Nakamura M, Shimizu, Yoshida Y, Takii Y, et al. Ishibashi H
    • Journal Title

      J Hepatol. 42(3)

      Pages : 386-392

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biliary epithelial cells regulate autoreactive T cells Implications for biliary-specific diseases.2005

    • Author(s)
      Kamihira T, Shimoda S, Nakamura M, Takii Y, et al.
    • Journal Title

      Hepatology 41

      Pages : 151-159

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis.2005

    • Author(s)
      Takii Y, Nakamura M, Ito M, Yokoyama T, Komori A et al., Ishibashi H
    • Journal Title

      Lab Invest. 85(7)

      Pages : 908-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hen and egg, you mitochondria! PBC revisits mitochondria again.2005

    • Author(s)
      Komori A, Ishibashi H
    • Journal Title

      Hepatol Res. 31(1)

      Pages : 1-2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ihterobserver variation in assessing small bile duct lesions in PBC, CVH, and AIH.2005

    • Author(s)
      Ito M, Ishibashi H.
    • Journal Title

      J Gastroenterol. 40(2)

      Pages : 223-224

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] T cell immunity in hepatitis B and hepatitis C virus infection : implications for autoimmunity.2005

    • Author(s)
      Ichiki Y, He XS, Shimoda S, Ishibashi H, Keeffe EB, Rossaro L, Gershwin ME.
    • Journal Title

      Autoimmun Rev. 4(2)

      Pages : 82-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis.2005

    • Author(s)
      Ichiki Y, Selmi C, Shimoda S, Ishibashi H, Gordon SC, Gershwin ME.
    • Journal Title

      Clin Rev Allergy Immunol. 28(2)

      Pages : 83-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] An active metabolite of leflunomide, A77 1726, inhibits the production of serum amyloid A protein in human hepatocytes.2005

    • Author(s)
      Migita K, Miyashita T, Maeda Y, Ishibashi H, et al.
    • Journal Title

      Rheumatology (Oxford)

      Pages : 443-448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells.2005

    • Author(s)
      Migita K, Maeda Y, Abiru S, Ishibashi H. et al.
    • Journal Title

      FEBS Lett. 579(14)

      Pages : 3119-3125

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatic expression of toll-like receptor 4 in primary biliary cirrhosis.2005

    • Author(s)
      Wang AP, Migita K, Ito M, et al., Ishibashi H
    • Journal Title

      J Autoimmun. 25(1)

      Pages : 85-91

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis.2005

    • Author(s)
      Mao TIC, Lian ZX, Selmi C, Ishibashi H, et al.
    • Journal Title

      Hepatology 42(4)

      Pages : 802-808

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fenofibrate-induced liver injury.2005

    • Author(s)
      Dohmen K, Wen CY, Nagaoka S, et al., Ishibashi H
    • Journal Title

      World J Gastroenterol. 11(48)

      Pages : 7702-7703

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The immune response to mitochondrial autoantigens.2005

    • Author(s)
      Ishibashi H, Shimoda S, Gershwin ME.
    • Journal Title

      Seminars in Liver Disease 25(3)

      Pages : 337-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis.2005

    • Author(s)
      Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T, Ueki T, Daikoku M, Yano K, Matsumoto T, Migita K, Yatsuhashi H, Ito M, Masaki N, Adachi H, Watanabe Y, Nakamura Y, Saoshiro T, Sodeyama T, Koga M, Shimoda S, Ishibashi H
    • Journal Title

      J.Hepatol. 42(3)

      Pages : 386-392

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatic expression of toll-like receptor 4 in primary biliary cirrhosis.2005

    • Author(s)
      Wang A-P, Migita K, Ito M, Takii Y, Daikoku M, Yokoyama T, Komori A, Nakamura M et al.
    • Journal Title

      J.Autoimmunity 25

      Pages : 85-91

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biliary epithelial cells regulate autoreactive T cells : Implications for biliary-specific diseases.2005

    • Author(s)
      Kamihira T, Shimoda S, Nakamura M, Yokoyama T, Takii Y, Kawano A et al.
    • Journal Title

      Hepatology 41

      Pages : 151-159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by interleukin-1beta in rheumatoid synovial fibroblasts.2005

    • Author(s)
      Migita K, Miyashita T, Ishibashi H, Eguchi K, et al.
    • Journal Title

      Immunology Letter 98(2)

      Pages : 194-199

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis.2005

    • Author(s)
      Takii Y, Nakamura M, Ito M, Yokoyama T, Komori A, Shimizu-Yoshida Y, Nakao R, Kusumoto K, Nagaoka S, Yano K, Abiru S, Ueki T, Matsumoto T, Daikoku M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Nakashima M, Harada M, Ishibashi H
    • Journal Title

      Lab Invest. 85(7)

      Pages : 908-920

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis.2005

    • Author(s)
      Mao TK, Lian ZX, Selmi C, Ichiki Y, Shimoda S, Ishibashi H, et al.
    • Journal Title

      Hepatology 42(4)

      Pages : 802-808

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells.2005

    • Author(s)
      Migita K, Maeda Y, Abiru S, Komori A, Nakamura M, Ishibashi H, et al.
    • Journal Title

      FEBS Letter 579(14)

      Pages : 3119-3125

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis.2005

    • Author(s)
      Takii Y, Nakamura M, Ito M, Yokoyama T, Komori A, Ishibashi H, et al.
    • Journal Title

      Laboratory Investigation 85(7)

      Pages : 908-205

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hepatic expression of toll-like receptor 4 in primary biliary cirrhosis.2005

    • Author(s)
      Wang AP, Migita K, Ito M, Takii Y, Nakamura M, Ishibashi H, et al.
    • Journal Title

      Journal of Autoimmunity 25(1)

      Pages : 85-91

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biliary epithelial cells regulate autoreactive T cells : implications for biliary-specific diseases.2005

    • Author(s)
      Kamihira T, Shimoda S, Nakamura M, Ishibashi H, et al.
    • Journal Title

      Hepatology 41(1)

      Pages : 151-159

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis.2005

    • Author(s)
      Nakamura M, Shimizu-Yoshida Y, Shimoda S, Ishibashi H, et al.
    • Journal Title

      Journal of Hepatology 42(3)

      Pages : 386-392

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hen and egg, you mitochondrial PBC revisits mitochondria again.2005

    • Author(s)
      Komori A, Ishibashi H
    • Journal Title

      Hepatol Research 31(1)

      Pages : 1-2

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fenofibrate for patients with asymptomatic primary biliary cirrhosis.2004

    • Author(s)
      Dohmen K, Mizuta T, Ishibashi H, et al.
    • Journal Title

      World J Gastroenterol 10(6)

      Pages : 894-898

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of IL- 18 in the modulation of matrix metalloproteinases and migration of human natural killer (NK) cells.2004

    • Author(s)
      Ishida Y, Migita K, Ishibashi H, et al.
    • Journal Title

      FEBS Lett. 569(1-3)

      Pages : 156-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Primary biliary cirrhosis in monozygotic and dizygotic twins : genetics, epigenetics, and environment.2004

    • Author(s)
      Selmi C, Mayo MJ, Ishibashi H, et al.
    • Journal Title

      Gastroenterology 127(2)

      Pages : 485-492

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Is primary biliary cirrhosis a model autoimmune disease?2004

    • Author(s)
      Ichiki Y, Shimoda S, Ishibashi H, Gershwin ME.
    • Journal Title

      Autoimmun Rev. 3(4)

      Pages : 331-336

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mitochondria and autoimmunity in primary biliary cirrhosis.2004

    • Author(s)
      Ichiki Y, Leung PSC, Ishibashi H, Coppel RL, Ansari AA, Gershwin AA
    • Journal Title

      Mitochondrion 4

      Pages : 743-753

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] T Cell Immunity in Primary Biliary Cirrhosis.2004

    • Author(s)
      Ishibashi H, Ichiki Y, Kamihira T, Shimoda S.
    • Journal Title

      Mucosal Immunology Update 14

      Pages : 10-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lipopolysaccharide signaling induces serum amyloid A (SAA) synthesis in human hepatocytes in vitro.2004

    • Author(s)
      Migita K, Abiru S, Nakamura M, Komori A, Yoshida Y, Yokoyama T, Daikoku M, Ueki T, Takii Y, Yano K, Yatsuhashi H, Eguchi K, Ishibashi H.
    • Journal Title

      FEBS Let. 569(1-3)

      Pages : 235-239

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Is primary biliary cirrhosis a model autoimmune disease?2004

    • Author(s)
      Ichiki Y, Shimoda S, Ishibashi H, Gershwin ME.
    • Journal Title

      Autoimmunity Review 3(4)

      Pages : 331-336

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Innate immune responses in human intrahepatic biliary epithelial cells via Toll-like receptors.2004

    • Author(s)
      Komori A, Yokoyama T, Takii Y, Nakamura M, Shimoda S et al.
    • Journal Title

      AASLD Abstract #597 (October 31, 2004. Boston)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-gp210 antibody titers as a clinical parameter that predicts the long-term outcome of primary biliary cirrhosis under ursodeoxycholic acid treatment.2004

    • Author(s)
      Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T et al.
    • Journal Title

      AASLD Abstract #679 (October 31, 2004. Boston)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Primary biliary cirrhosis in monozygotic and dizygotic twins : genetics, epigenetics, and environment.2004

    • Author(s)
      Selmi C, Mayo MJ, Bach N, Ishibashi H, et al.
    • Journal Title

      Gastroenterology 127(2)

      Pages : 485-492

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Is primary biliary cirrhosis a model autoimmune disease?2004

    • Author(s)
      Ichiki Y, Shimoda S, Ishibashi H, Gershwin ME
    • Journal Title

      Autoimmunity Reviewiew 3(4)

      Pages : 331-336

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mitochondria and autoimmunity in primary biliary cirrhosis.2004

    • Author(s)
      Ichiki Y, Leung PSC, Ishibashi H, et al.
    • Journal Title

      Mitochondrion 4

      Pages : 743-753

    • Related Report
      2004 Annual Research Report
  • [Journal Article] T Cell Immunity in Primary Biliary Cirrhosis.2004

    • Author(s)
      Ishibashi H, Ichiki Y, Kamihira T, Shimoda S
    • Journal Title

      Mucosal Immunology Update 14

      Pages : 10-12

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of distinct costimulation dependent and independent autoreactive T cell clones in primary biliary cirrhosis.2003

    • Author(s)
      Kamihira T, Shimoda S, Harada K, Kawano A, et al.
    • Journal Title

      Gastroenterology 125

      Pages : 1379-87

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis.2003

    • Author(s)
      Shimoda S, Nakamura M, Ishibashi H, et al.
    • Journal Title

      Gastroenterology 124

      Pages : 1915-1925

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis.2003

    • Author(s)
      Masuda J, Omagari K, Ishibashi H, et al.
    • Journal Title

      Dig Dis Sci. 48(5)

      Pages : 932-938

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Promiscuous T cells selected by Escherichia coli : OGDC-E2 in primary biliary cirrhosis.2003

    • Author(s)
      Tanimoto H, Shimoda S, Ishibashi H, et al.
    • Journal Title

      J Autoimmun. 20(3)

      Pages : 255-263

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis.2003

    • Author(s)
      Kamihira T, Shimoda S, Harada K, Kawano A, Handa M, Baba E, Tsuneyama K, Nakamura M, Ishibashi H, Nakanuma Y, Gershwin ME, Harada M.
    • Journal Title

      Gastroenterology 125(5)

      Pages : 1379-1387

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis2003

    • Author(s)
      Masuda J, Omagari K, Ohba K, Hazama H, Kadokawa Y, Kinoshita H, Hayashida K, Ishibashi H, et al.
    • Journal Title

      Digestive Disease and Sciences 48(5)

      Pages : 932-938

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of distinct costimulation dependent and independent autoreactive T cell clones in primary biliary cirrhosis.2003

    • Author(s)
      Kamihira T, Shimoda S, Harada K, Kawano A, Handa M, Baba E, Tsuneyama K, Nakamura M, Ishibashi H, et al.
    • Journal Title

      Gastroenterology 125

      Pages : 1379-1387

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] T cell immunity and primary biliary cirrhosis.2003

    • Author(s)
      Ishibashi H., Nakamura M, Shimoda S, Gershwin ME.
    • Journal Title

      Autoimmunity Reviews 2(1)

      Pages : 19-24

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 肝臓病の最新治療(戸田剛太郎,沖田極,門田守人,井廻道夫,幕内雅敏,恩地森一,森正樹,茶山一彰,持田智,銭谷幹男編集)2006

    • Author(s)
      石橋大海, 下田慎治, 中村稔
    • Total Pages
      406
    • Publisher
      先端医療技術研究所
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 肝臓病学(井廻道夫,坪内博仁,熊田博光,林 紀夫編集)2006

    • Author(s)
      石橋大海
    • Total Pages
      504
    • Publisher
      朝倉書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 今日の治療指針-私はこう治療している2006年版2006

    • Author(s)
      石橋大海
    • Total Pages
      1726
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 臨床検査診断マニュアル 改訂第2版(古澤新平,金山正明,橋本博史(編))2006

    • Author(s)
      石橋大海
    • Total Pages
      858
    • Publisher
      永井書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 肝疾患と免疫(各務伸一編)2006

    • Author(s)
      小森敦正, 中村稔, 石橋大海
    • Total Pages
      179
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 疾患別最新処方、改訂第4版(矢崎義雄、菅野健太郎監修)2006

    • Author(s)
      石橋大海
    • Total Pages
      956
    • Publisher
      メジカルビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 専門医のための消化器病学(小俣政男・千葉勉/監修)2006

    • Author(s)
      石橋大海
    • Total Pages
      637
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] ナーシングケアQ&A ここまで知っておきたい くすりとナーシングQ&A2006

    • Author(s)
      阿比留正剛, 石橋大海
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 臨床消化器病学(石井裕正,朝倉 均,税所宏光,幕内博康編集)2006

    • Author(s)
      一木康則, 石橋大海
    • Publisher
      朝倉書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 消化器疾患診療実践ガイド.診療室ですぐに薬龍卓上リファレンス(千葉 勉,井廻道夫編集,伊藤俊之編集協力)2006

    • Author(s)
      石橋大海
    • Total Pages
      973
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 専門医のための消化器病学2005

    • Author(s)
      石橋 大海
    • Total Pages
      637
    • Publisher
      医学書院
    • Related Report
      2005 Annual Research Report
  • [Book] The Pathophysiology of the Biliary Epithelia,2004

    • Author(s)
      Shinji Shimoda, Akiyoshi Nishio, Hiromi Ishibashi,, M.Eric Gershwin
    • Total Pages
      454
    • Publisher
      LANDES BIOSCIENCE, GEORGETOWN, EUREKAH. COM, AUSTIN
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Tanimoto H, Shimoda S, Nakamura M, Ishibashi H, Gershwin M.E, Harada M: "Promiscuous T cells selected by Escherichia coli OGDC-E2 in primary biliary cirrhosis"Autoimmunity. 20. 255-263 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimoda S, Nakamura M, Ishibashi H, et al.: "Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis."Gastroenterology. 124. 1915-1925 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kamihira T, Shimoda S, Harada K, Kawano A, Handa M, Baba E, Tsuneyama K, Nakamura M, Ishibashi H, et al.: "Characterization of distinct costimulation dependent and independent autoreactive T cell clones in primary biliary cirrhosis"Gastroenterology. 125. 1379-1387 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masuda J, Omagari K, Ohba K, Hazama H, Kadokawa Y, Kinoshita H, Hayashida K, Ishibashi H, et al.: "Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis."Digestive Disease and Sciences. 48(5). 932-938 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishibashi H, Nakamura M, Shimoda S, Gershwin ME: "T cell immunity and primary biliary cirrhosis"Autoimmunity Reviews. 2(1). 19-24 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中村 稔, 下田慎治, 石橋大海: "原発性胆汁性肝硬変の成因-ミトコンドリア抗原と免疫応答"臨床消化器内科. 18. 545-551 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinji Shimoda, Akiyoshi Nishio, Hiromi Ishibashi, M.Eric Gershwin: "The Pathophysiology of the Biliary Epithelia"Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, and Nicholas LaRusso.. 454 (2003)

    • Related Report
      2003 Annual Research Report

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Published : 2003-04-01   Modified : 2016-04-21  

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