| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
A : The results of the study on Hemolytic uremic Syndrome (HUS). (1) BALB/c mice were intraperitoneally infected with 1x10^5 CFU of Enterohemorrhagic E.coli (EHEC, sero-type O157, strain; T1001). Then, they were intraperitoneally injected with 50μg of LPS, in order to elicit HUS. Kindneys were obtained at 0, 3 and 8 days after LPS injection, and the expression levels of mRNA of IFN-γ, TNF-α and iNOS were examined by RNA-PCR. As the result, the expression levels of mRNA of IFN-γ and TNF-α were significantly enhanced. A marked expression of iNOS-mRNA was also observed, suggesting that such proinflammatory cytokines as IFN-γ and TNF-α induced iNOS. (2) Inducible nitric oxide synthase (iNOS) gene-disrupted mice (iNOS-/-) and their wild type controls (iNOS+/+) were intraperitoneally infected with 1x10^5 CFU of Enterohemorrhagic E.coli (EHEC, sero-type O157, strain; T1001). Then, they were intraperitoneally injected with 50μg of LPS. At 3 days after LPS injection, the number of the bacteria in the intestines of iNOS-/- mice was significantly increased than that in iNOS+/+ mice. However, the renal lesions could not be observed in iNOS-/- mice, whereas they could be seen in iNOS+/+ mice. Thus, in conclusion, the renal complications after EHEC infection was not due to direct effect of the bacteria but due to NO.
B : The results of other studies We performed several other studies using iNOS-/- mice, which were developed for this project on HUS. (1) Cytomegalovirus (CMV) infection : NO played a protective role against CMV infection, however NO also acted as pathogenic factor in CMV-associated pneumonitis. Thus, NO possessed the beneficial and pathogenic effects in CMV infection. (2) A therosclerosis; NO decreased extracellular collagen content in atherosclerosis lesions.
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