|Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
1.We have tested the feasibility of measuring various chemokine gene expression using RT-PCR method in urine of kidney recipients as non-invasive diagnosis method of acute rejection. We were able to detect the gene expression of RANTES, MCP-1, MCP-2, IP-10, IL-8, Mig, MIP-1α, MIP-1β, ENA-78, Eotaxin in the urine from the renal transplant recipients. Moreover, the gene expression of Mig, RANTES and MCP-1 was specifically detected in urine of reanl transplant recipient at the time of acute rejection. These gene expression were detected earlier than the clinical diagnosis were made by the standard methods such as blood test or allograft biopsy.
2.It has been recognized that renal blood flow is regulated by the balance of vasoconstrictive and vasodilating agents such as angiotensin II, endothelin (ET) and nitric oxide (NO). However, Cyclosporine (CYA) and tacrolimus (TAC) are well studied as calcinurine inhibitors (CNI) on its immunological effects, its vasoconstrictive effects have been also reported as the mechanisms of their nephrotoxicity. We have tested the acute effects of CYA and TAC on renal vascular tone that could relate to their nephrotoxicity. Blockade of NO production enhanced vasoconstrictive effect of CYA, and unmasked such effect of TAC. These results suggest that CYA and TAC may involve NO system in their nephrotoxicity.