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A study of the mechanism of bone marrow failure in hepatitis-associated aplastic anemia.

Research Project

Project/Area Number 13670792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

KOJIMA Seiji  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20313992)

Co-Investigator(Kenkyū-buntansha) KIMURA Hiroshi  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30303621)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHepatitis / Aplastic Anemia / Apoptosis / Fas antigen / Hepatitis E / HLA / E型肝炎ウィルス / パルボB19ウィルス
Research Abstract

Hepatitis-associated aplastic anemia (H-AA) is a varient of acquired AA, in which hepatitis precedes AA by a period of weeks to months. Both etiology of hepatitis and a mechanism of bone marrow failure are unknown. Although hepatitis E virus (HEV) was studied by HEVIgG and HEVIgM in 16 patients with H-AA, it was not detected in all of them. Based on our result, it is concluded that HEV is not a candidate virus for H-AA. We studied HLA antigen in 30pts. with H-AA, 60pts. with idiopathic AA and 250 normal controls. The frequencies of DR9 antigen was significantly increased in the pts. with H-AA, compared to pts, with idiopathic AA or normal controls (relative risk : 4.1). In pts with HAA, absolute numbers of total lymphocytes, especially CD4 lymphocytes are markedly decreased. We analyzed the expression of Fas antigen on peripheral lymphocytes and BM CD34+cells of pts. with AA. Higher expression of Fas antigen on peripheral lymphocytes and BM CD34+cells was found in pts. with H-AA than in pts. with idiopathic AA or normal controls. Expression of Fas-ligand was also increased on peripheral and BM CD+3 lymphocytes. These results suggest that increased programmed cell death though Fas/Fas ligand system in HLA restricted individuals is a possible mechanism of bone marrow failure in pts. with H-AA.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Tanaka N, Kojima S, et al.: "Expression of tegument protein pp65 of human cytomegalovirus (CMV) and its application to the analysis of viral-specific cellular immunity in CMV-infected individuals"Arch Virol. 147. 2045-2417 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ihara M, Kojima S, et al.: "Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR ; comparison to detection of viral DNA in plasma by qualitative PCR"Microbiol Immunol.. 46. 701-705 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo Y, Kojima S, et al.: "Transient pancytopenia associated with parvovirus infection in a healthy child"Pediatr Int.. 44. 695-697 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima S, et al.: "Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children"Blood. 100. 786-790 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima S, et al.: "Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors : The Japan Marrow Donor Program"Blood. 100. 799-803 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohga S, Kojima S, et al.: "Treatment response of childhood aplastic anemia with chromosomal aberrations at diagnosis"Br J Haematol. 118. 313-319 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kudo K, Kojima S, et al.: "Successful engraftment of unrelated donor stem cells in two children with congenital amegakaryocytic thrombocytopenia (CAMT)"J Pediatr Hematol Oncol. 24. 79-80 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yosiwaka T, Kojima S, et al.: "Human herpesvirus 6 viremia in bone marrow transplant recipients : clinical features and risk factors"J Infect Dis. 185. 847-853 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshimi A, Kojima S, et al.: "Epstein-Barr virus specific T cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation"Br J Haematol. 116. 710-715 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohara A, Kojima S, et al.: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"Br J Haematol. 116. 999-1010 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manabe A, Kojima S, et al.: "Allogeneic hematopoietic stem cell transplantaton for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the international JMML working Group"Leukemia. 16. 645-649 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima s: "Unrelated donor marrow transplantation on children with severe aplastic anemia using cyclophosphamide, antii-thymocyte globulin and total body irradiation"Br J of Haemat. 114. 706-711 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki H, Kojima S et al.: "Myelodysplastic syndrome in childhood : A retrospective of 189 patients in Japan"Leukemia. 15. 1713-1720 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T, Kojima S et al.: "Correlation between HHV6 infection and skin rash after allogeneic bone marrow transplantation"Bone Marrow Transplant. 28. 77-81 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hoshino Y, Kojima S et al.: "Prospective monitoring of the Epstein-Barr virus DNA by a real-time Quantitative polymerase chain reaction after allogeneic stem cell transplantation"Br J of Haemat. 115. 105-111 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo M, Kojima S et al.: "Risk factors for chronic graft-versus-host disease after allogeneic stem cell taransplantation in children"Bone marrow transplant. 27. 727-730 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka N, Kojima S, et al: "Expression of tegument protein pp65 of human cytomegalovirus (CMV) and its application to the analysis of viral-specific cellular immunity in CMV-infected individuals"Arch Virol. 147. 2405-2417 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ihira M, Kojima S, et al: "Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR ; comparison to detection of viral DNA in plasma by qualitative PCR"Microbiol Immunol. 46. 701-705 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo Y, Kojima S, et al: "Transient pancytopenia associated with parvovirus infection in a healthy child"Pediatr Int. 44. 695-697 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima S, et al: "Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children"Blood. 100. 786-790 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima S, et al: "Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors : The Japan Marrow Donor Program"Blood. 100. 799-803 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohga S, Kojima S, et al: "Treatment responses of childhood aplastic anaemia with chromosomal aberrations at diagnosis"Br J Haematol. 118. 313-319 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kudo K, Kojima S, et al: "Successful engraftment of unrelated donor stem cells in two children with congenital amegakaryocytic thrombocytopenia (CAMT)"J Pediatr Hematol Oncol. 24. 79-80 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T, Kojima S, et al: "Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors"J Infect Dis. 185. 847-853 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshimi A, Kojima S, et al: "Epstein-Barr virus specific T cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation"Br J Haematol. 116. 710-715 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohara A, Kojima S, et al: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"Br J Haematol. 116. 999-1010 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Manabe A, Kojima S, et al: "Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group"Leukemia. 16. 645-649 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima S, et al: "Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiaion"Br J Haematol. 114. 706-711 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki H, Kojima S et al: "Myelodysplastic syndrome in childhood : A retrospective of 189 patients in Japan"Br J Haematol. 15. 1713-1720 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshikawa T, Kojima S, et al: "Correlation between HHV-6 infection and skin eruptions after allogeneic bone marrow transplantation"Bone Marrow Transplant. 28. 77-81 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hoshino Y, Kojima S, et al: "Prospective monitoring of the Epstein-Barr virus DNA by a real-time quantitative polymerase chain reaction after allogenic stem cell transplantation"Br J Haematol. 115. 105-111 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo M, Kojima S, et al: "Risk factors for chronic graft- versus-host disease after allogeneic stem cell transplantation in children"Bone Marrow Transplant. 27. 727-730 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka N, Kojima S, et al.: "Expression of tegument protein pp65 of human cytomegalovirus (CMV) and its application to the analysis of viral-specific cellular immunity in CMV-infected individuals"Arch Virol. 147. 2045-2417 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ihara M, Kojima S, et al.: "Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR ; comparison to detection of viral DNA in plasma by qualitative PCR"Microbiol Immunol.. 46. 701-705 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kondo Y, Kojima S, et al.: "Transient pancytopenia associated with parvovirus infection in a healthy child"Pediatr Int.. 44. 695-697 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kojima S, et al.: "Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children"Blood. 100. 786-790 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kojima S, et al.: "Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors : The Japan Marrow Donor Program"Blood. 100. 799-803 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohga S, Kojima S, et al.: "Treatment response of childhood aplastic anemia with chromosomal aberrations at diagnosis"Br J Haematol. 118. 313-319 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kudo K, Kojima S, et al.: "Successful engraftment of unrelated donor stem cells in two children with congenital amegakaryocytic thrombocytopenia(CAMT)"J Pediatr Hematol Oncol. 24. 79-80 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T, Kojima S, et al.: "Human herpesvirus 6 viremia in bone marrow transplant recipients : clinical features and risk factors"J Infect Dis. 185. 847-853 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimi A, Kojima S. et al.: "Epstein-Barr virus specific T cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation"Br J Haematol. 116. 710-715 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohara A, Kojima S. et al.: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"Br J Haematol. 116. 999-1010 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Manabe A, Kojima S, et al.: "Allogeneic hematopoietic stem cell trransplantaton for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the international JMML working Group"Leukemia. 16. 645-649 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kondo M: "Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children"Bone Marrow Transplant. 27. 727-730 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kojima S: "Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation"British Journal of Haematology. 114. 706-711 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sasaki H: "Myelodysplastic syndrome in childhood : A retrospective of 189 patients in Japan"Leukemia. 15. 1713-1720 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshikawa T: "Correlation between HHV6 infection and skin rash after allogeneic bone marrow transplantation"Bone Marrow Transplant. 28. 77-81 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hoshino Y: "Prospective monitoring of the Epstein-Barr virus DNA by a real-time quantitative polymerase chain reaction after allogeneic stem cell transplantation"British Journal of Haematology. 115. 105-111 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohara A: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"British Journal of Haematology. 116. 151-154 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kudo K: "Successful engraftment of unrelated donor stem cell in two children with congentiqal amegakaryocytic thrombocytopenia(CMT)"J Pediatric Hematology/Oncology. 24. 79-80 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimi A: "Epstein-Barr virus specific T cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation"British Journal of Haematology. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshikawa T: "Human herpesvirus 6 viremia in bone marrow transplant recipients : Clinical features and risk factors"J Infection Disease. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Manabe A: "Allogeneis hematopoietic stem transplantation for 24 children with juvenile myelomonocytic leukemia diagnosed based on the criteria by the International JMML working Group"Leukemia. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 中畑 龍俊: "第一回MDS委員会活動報告書"日本小児血液学会雑誌. 15. 54-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋 義行: "小児の症候群PNH-aplastic anemia症候群"小児科診療. 64. 202 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小島 勢二: "小児期にみられる貧血の治療"小児保健研究. 60. 165-171 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小島 勢二: "私の処方 2001-小児薬物治療の実際-再生不良性貧血"小児科臨床. 54. 726 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小島 勢二: "小児疾患の診断治療基準 再生不良性貧血"小児内科. 33. 524-525 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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