| Project/Area Number |
61870048
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | University of Tokyo |
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Principal Investigator |
OKABE Tetsurou Faculty of Medicine, University of Tokyo, 医学部(病), 助手 (80169135)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Kouichi Faculty of Medicine, University of Tokyo, 医学部(病), 医員
WATANABE Junichi Institute of Medical Sciences, University of Tokyo, 医科学研究所, 助手 (20201189)
FUJISAWA Michio Faculty of Medicine, University of Tokyo, 医学部(病), 医員 (60218998)
URABE Akio Faculty of Medicine, University of Tokyo, 医学部(病), 講師 (60142246)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥24,500,000 (Direct Cost: ¥24,500,000)
Fiscal Year 1988: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1987: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1986: ¥11,500,000 (Direct Cost: ¥11,500,000)
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| Keywords | Colony stimulating factor / Cancer / Granulocytopenia / Bonemarrow Transplantation / Chemotherapy / 放射線照射 / G-CSF / 受容体 / 白血病 / 胎盤 / 白血球 / Granulocyte colony-stimulating factor / Recombinant / Granulocytosis |
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| Research Abstract |
Recombinant human granulocyte colony-stimulating factor (Re Hu G-CSF) was prepared and its stimulating effect on granulocytopoiesis was examined in mice. Human G-CSF was purified to homogeneity from conditioned media of a G-CSF producing cell line. The amino-terminal sequence was determined. By using okigonucleotides as probes, which were proposed by the amino acid sequence, a cDNA library prepared from human macrophages was screened. The cloned G-CSF cDNA was expressed in E.coli K12MM294,and themature protein was purified to homogeneity. Mice were given intraperitoneal injections of Re Hu-G-CSF everyday for 14 day. Peripheral blood granulocyte counts were examined after 4, 8, 12, and 14 days of injection. Mice were sacrificed on the 14th day for histologic examinations of bone marrow, and spleen. Granulocyte counts began to increase on the 4th day and reached about 80,000/mm on the 14th day. Cells of granulocyte lineage were markedly increased in the bone marrow and spleen. Granulocyte precursors (CFC-C) were remarkably increased in the spleen. When mice were treated with 5-fluorouracil, cyclophophosphamide, or irradiation, the period of granulocytopenia was significantly shortened by subcutaneous injections of Re Hu G-CSF. These results suggest that human G-CSF play a central role in granulocyte production in vivo. The ability of Re Hu G-CSF to stimulate granulocyte production implies that this factor will be clinically useful in neutropenic patients treated with anti-cancer agents or irradiation.
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