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Basic and Clinical Studies of the Refulation Mechanisms of Human Megakaryocytopoiesis

Research Project

Project/Area Number 01480302
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionTokyo Women's Medical College

Principal Investigator

MIZOGUCHI Hideaki  Tokyo Women'S Medical College Professor, 医学部, 教授 (70049021)

Co-Investigator(Kenkyū-buntansha) TERAMURA Masanao  Tokyo Women's Medical college Assistant, 医学部, 助手 (40188686)
YAMADA Osamu  Tokyo Women's Medical College Assistant, 医学部, 助手 (30167712)
OSHIMI Kazuo  Tokyo Women's Medical College Assistant Prof., 医学部, 助教授 (40089991)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsthrombopoietin / IL-6 / IL-7 / IL-11 / stem cell factor / 巨核球コロニ-刺激因子 / 巨核球増幅因子 / GMーCSF / GーCSF / ILー3 / エリスロポエチン
Research Abstract

1. By the culture of human marrow cells for megakaryocyte colony formation in serum-free conditions, it was confirmed that IL-3 and GM-CSF have megakaryocyte CSF activity. Erythropoietin (EPO), M-CSF, IL-6, IL-7 and stem cell factor (SCF) have the activity of megakaryocyte potentiator. There is a possibility that these cytokines play a role in the regulation of thrombopoiesis in vivo. G-CSF and IL-9 have no effect on megakaryocyte colony formation.
2. When various cytokines were added to CMK cells to see their effect on the incorporation of 3H-TdR, IL-3, GM-CSF, IL-6, IL-11 and SCF have stimulatory activity. There is a possibility that these cytokines play a role in the regulation of thrombopoiesis in vivo. EPO, IL-7, IL-9 and leukemia inhibitctor have no effect on the proliferation of CMK cells.
When we fractionated the urine from a thrombocytopenic patient by ammonium sulfate, the sediment fractionated by 50% ammonium sulfate has stimulatory effect on CMK Cells. It was confirmed that the stimulatory effect of this fraction is caused by the factors other than EPO, IL-1alpha, IL-1beta, IL-3, GM-CSF, IL-6 or TNF-alpha.
3. When the IL-6 concentration of the patients with aplastic anemia was measured by ELISA, the increase in IL-6 was not observed. From these findings, it could be considered that IL-6 is not produced in response to thrombocytopenia in case of aplastic anemia.
4. It was shown that peripheral blood mononuclear cells from the patients with essential thrombocythemia or CML responded to the lower concentration of IL-3 than those of normal controls.
5. DNA fractionated by an pulse field electrophoresis from the leukemic cells of the patients with myeloproliferative disorders with thrombocytosis were hybridized to transferrin gene or somatostatin gene probes for the detection of chromosome abnormalities in the long arm of chromosome 3, but we could not detect any abnormalities so far.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Sato T,Fuse A,Eguchi M,Hayashi Y,Ryo R,Adachi M,Kishimoto Y,Teramura M,Mizoguchi H,Shima T,et al: "Establishment of a human leukaemic cell line(CMK)with megakaryocytic characteristics from a Down's syndrome patient with acute megakaryoblstic leukaemia." Br J Haematol. 72. 184-190 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Teramura M,Katahira J,Hoshino S,Motoji T,Oshimi K,Mizoguchi H: "Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serumーfree cultures." Exp Hematol. 17. 1011-1016 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshimi K,Shinkai Y,Okumura K,Oshimi Y,Mizoguchi H: "Perforin gene expression in granular lymphocyte proliferative disorders." Blood. 75. 704-708 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Motoji T,Okada M,Takanashi M,Masuda M,Tanaka K,Oshimi K,Mizoguchi H: "Induction of eosinophilic colonies by interleukinー5 on acute myeloblastic leukaemic cells." Br J Haematol. 74. 169-172 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshimi K,Oshimi Y,Yamada O,Wada M,Hara T,Mizoguchi H: "Cytotoxic T lymphocyte triggering via CD16 is regulated by CD3 and CD8 antigens: Studies with T cell receptor (TCR)ーαβ^+/CD3^+16^+and TCR-γδ^+/CD3^+16^+granular lymphocytes." J Immunol. 144. 3312-3317 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Teramura M,Mizoguchi H: "The effect of cytokines on the ploidy of megakaryocytes." Int J Cell Cloning. 8. 245-252 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sato T, Fuse A, Eguchi M, Hayashi Y, Ryo R, Adachi M, Kishimoto Y, Teramura M, Mizoguchi H, Shima Y, Komori I, Sunami S, Okimoto Y, Nakajima H: "Establishment of a human leukaemic cell line (CMK) with megakaryocytic characteristics from a Doun's syndrome patient with acute megakaryoblasic leukaemia." Br J Haematol. 72. 184-190 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Teramura M, Katahira J, Hoshino S, Motoji T, Oshimi K, Mizoguchi H: "Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum free cultures." Exp Hematol. 17. 1011-1016 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshimi K, Shinkai Y, Okumura K, Oshimi Y, Mizoguchi H: "Perforin gene expression in granular lymphocyte proliferative desorders." Blood. 75. 704-708 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Motoji T, Okada M, Takanashi M, Masuda M, Tanaka k, Oshimi K, Mizoguchi H: "Induction of eosinophilic colonies by interleukin-5 on acute myeloblasic leukaemic cells." Br J Haematol. 74. 169-172 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshimi K, Oshimi Y, Yamada O, Wada M, Hara T, Mizoguchi H: "Cytotoxic T lymphocyte triggering via CD16 is regulated by CD3 and CD8 antigens : Studies with T cell receptor (TCR) -alphabeta^+/CD3^+ 16^+ and TCR-gammadelta^+/CD3^+16^+ granular lymphocytes." J Immunol. 144. 3312-3317 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Teramura M, Mizoguchi H: "The effect of cytokines on the ploidy of megakaryocytes." Int J Cell Cloning. 8. 245-252 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Oshimi K,Shinkai Y,Okumura K,Osimi Y,Mizoguchi H: "Perforin gene expression in granular lymphocyte proliferative disorders." Blood. 75. 704-708 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Motoji t,Okada M,Takanashi M,Masuda M,Tanaka K,Oshimi K,Mizoguchi H: "Induction of eosinophilic colonies by interleukinー5 on acute myeloblastic leukaemic cells." Br J Haematol. 74. 169-172 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Teramura M,Mizoguchi H: "The effect of cytokines on the ploidy of megakaryocytes." Int J Cell Cloning. 8. 245-252 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hoshino S,Oshimi K,Tsudo M,Miyasaka M,Teramura M,Masuda M,Motoji T,Mizoguchi H: "Flow cytometric analysis of expression of interleukinー2 receptor β chain (p70ー75) on various leukemic cells." Blood. 76. 767-774 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Masuda M,Motoji T,Oshimi K,Mizoguchi H: "Effect of interleukinー7 on proliferation of hematopoietic malignant cells." Exp Hematol. 18. 965-967 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Motoji T,Watanabe M,Uzumaki H,Kusaka K,Fukamachi H,Shimosaka A,Oshimi K,Mizoguchi: "Granulocyte colonyーstimulating factor (GーCSF) receptors on acute myeloblastic leukaemia cells and their relationship with the proliferative response to GーCSF in clonogenic assay." Br J Haematol. 77. 54-59 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Mizoguchi H: "Hemopoiesis and immune mechanisme" Acta Haematologica Japonica. 52. 1251-1257 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Masuda M,Takanashi M,Motoji T,Oshimi K,Mizoguchi H: "Effect of recombinant interterons on hairy cell leukemia progenitors" International Jounal of Cell Cloning. 7. 120-128 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hoshino S,Teramura M,Takahashi M,Motoji T,Oshimi K,Ueda M,Mizoguchi H: "Expression and characterization of erythropoietin receptors on normal human bone marrow cells" International Jounal of Cell Cloning. 7. 156-167 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sato T,Fuse A,Eguchi M,Hayashi Y,Ryo R,Adachi M,Kishimoto Y,Teramura M,Mizoguchi H,et al: "Estabishment of a human leukaemic cell line(CMK)with megakaryocytic characteristics from a Down's syndrome patient with acute megakaryoblastic leukaemia" Britishi Jounal of Haematology. 72. 184-190 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Teramura M,Katahira J,Hoshino S,Motoji T,Oshimi K,Mizoguchi H: "Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures" Experimental Hematology. 17. 1011-1016 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mori N,Yokota J,Oshimura M,Cabenee WK,Mizoguchi H,Noguchi M,Shimosato Y,Sugimura T,Terada M: "Concordant deletions of chromosome 3p and loss of heterozygosity for chromosones 13 and 17 in small cell lung carcinoma" Cancer Research. 49. 5130-5135 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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