| Project/Area Number |
10670994
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
YUZAWA Yukio Nagoya University, School of Medicine, Research Assoc., 医学部, 助手 (00191479)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Masashi Nagoya University, School of Medicine, Research Assoc., 医学部, 助手 (20303638)
MATSUO Seiichi Nagoya University, School of Medicine, Assis. Professor, 医学部, 講師 (70190410)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | glomerular thrombus / progressive renal injury / adhesion molecule / selectin / sulfatide / sulfotransferase / synthetic carbohydrate / 糖移転酵素 |
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| Research Abstract |
The aim of this project was to investigate the role of selections and selectin ligands in the formation of glomerular thrombi, since glomerular thrombi occurs various glomerular diseases and is an important pathological parameter for the progressive renal injuries. In the present study, the role of P-selectin in the formation of glomerular thrombi and the therapeutical effects of synthetic selectin blocker were studied. In the first part of experiment using a rat model of thrombotic microangiopathy induced by injection of subnephritic dose of LPS followed by nephrotoxic globulin,the following results were obtained. (1) The formation of microthrombi completely depended on the leukocyte infiltration in glomeruli, since depletion of circulating leukocytes by cyclophosphamide completely blocked the formation on thrombi. (2) Selective expression of P-selectin in glomeruli was detected. Anti P-selectin antibody prominently blocked platelets aggregation in glomeruli at 10 minutes, and signifi
… More
cantly blocked the infiltration of leukocytes and the formation thrombi at 6 hrs. (3) P-selectin receptor-blocking synthetic sulfatide derivative (SKK-60037) showed similar protective effects on the formation glomerular thrombi as those of anti P-selection antibody. These results indicate that P-selectin was significantly involved in the process of the formation on microthrombi, and synthetic sulfatide derivative (SKK-60037) may have potential for clinical application of progressive renal injuries. In the second part, the expression of N-acetylglucosamine-6-o-sulfotransferase mRNA was detected in the epitopes induced by this enzyme in fetal kidneys was studied. The results were as follow ; although prominent expression of N-acetylglucosamine-6-o-sulfotransferase mRNA was detected in the epithelial cells, the epitopes such as 6-sulfo LewisX or 6-sulfo sialyl Lewis X were not detected in fetal kidneys. These results indicate that the additional expression of fucosyltransferases and/or sialyltransferases might be requisite for expression of selectin ligands in the kidney. Less
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