| Project/Area Number |
02454345
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
OCHI Takahiro MD,Osaka University Medical School Dept of Environmental Medicine, Professor, 医学部, 教授 (80112035)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Tomoatu MD,Osaka University Medical School Department of Orthopedics, Lecturer, 医学部, 講師 (80167379)
ONO Keiro MD,Osaka University Medical School, Department of Orthopedics, Professor, 医学部, 教授 (70028330)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | rheumatoid arthritis / iliac bone marrow / epiphyseal bone marrow / myeloid cells / activated CD8(+) T cells / IL-6,-8 / 関節破壊 / 重症病型 / MY4抗原 / GMCSF / 特異な骨髄球系カスケ-ド / MY4(+) / 組織破壊活性 / ILー1 |
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| Research Abstract |
Main purpose is to study the role of bone marrow in inducing or persisting poly-arthritis like rheumatoid arthritis. In experimental polyarthritis, pathological changes were seen primarily in bone marrow. Preceding the beginning of synovial proliferation, the cellular development and proliferation of bone marrow cells and the elevation of IL-1 and -6 could be observed in bone marrow. Thus, the role of bone marrow in inducing polyarthritis were impressed.
In the persistent severe inflammatory process of RA, some uncontrollable proliferation of a certain type of undifferentiated cells could be accompanied by destruction and disorganization of normal cells. We found an accumulation of abnormal myeloid lineage bearing aberrant carbohydrate membrane structures in the bone marrow of patients with severe active rheumatoid arthritis. Polymorphonuclear leukocytes, mature cells of myeloid lineage, accumulating in these lesions were found to contain unususally high levels of IL-1.
We further survey
… More
ed bone marrow of ilium as a systemic hemopoietic organ. In iliac bone marrow, numbers of each mononuclear cell fractions were highly significantly increased. The increase of activated (HLADR+) CD8 cells were significant. in iliac bone marrow of RA patients with both severe and mild natural course. The increase of myeloid cells in iliac bone marrow was significant in patients with severe destructive disease of RA. The abnormal myeloid cells primarily found in the epiphyseal bone marrow were found to accumulate much more in the iliac bone marrow of patients with severe destructive RA.
Cytokines were also surveyed in bone marrows. In the iliac bone marrow of RA patients, elevation of IL-6, and IL-8 were characteristically found. The elevation of these cytokines in peripheral blood were also found, but the levels were much less than those in the iliac bone marrow. Interestingly, the elevation of IL-6, -8 showed close relationships with exacerbation of synovitis in multiple joints.
Thus, in RA patients, iliac bone marrow could be a primarily important lesion, and could influence the peripheral blood and epiphyseal bone marrow. We are further surveying the roles of bone marrow in inducing RA. Less
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