Objective To study the effect of genomic HLA-DR compatibility on long-term survival in renal transplantation.Methods A retrospective study was performed on 518 first-cadaver renal transplants by using genotyping technique.Results More than 10%recipients shared HLA-DR matching at DNA level.half of 1 DR mismatches.The recipients with HLA-DR matched transplants showed a significant decrease of acute rejection episodes and a smooth recovery of early renal function as compared with those of DR mismatching kidneys.The 1 to 5 year-person survival rate was increased by 17%to 37.7% (P＜0.01)respectively.Multivariate analysis of 10 variables by Cox regression model revealed that DR mismatching was the most important factors influencing the long-term graft survival.Conclusion Genomic HLA-DR compatibility had a significant impact on long-term survival of first-cadaver kidney transplantation.

Objective To explore the single point target concentration for Neoral at 2 h postdose (C2) in Chinese renal transplantation recipients for the first 3 months following surgical procedures. Methods Neoral trough levels (C0) and C2 monitoring were measured by fluorescence polarization immunoassay (TDX) in 114 cases of cadaver renal transplants treated with Neoral (6～7 mg?kg -1 ?d -1 ), mycopherolate mofetil (MMF,1.0～1.5 g/d) and steroids for the first 3 months after renal transplantation.The effectiveness of the new monitoring method in predicting the acute rejection and side effects was retrospectively analyzed. Results The acute rejection rate of 114 transplants for the first 3 months was 15.8%(18/114).The incidence of side effects was 30.7% (35/114),including hepatoxicity(26.3%) and nephrotoxicity(7.0%).The results of 234 pairs of Neoral C0, C2 monitoring showed that the difference was not statistically significant between C0 levels of rejection and non rejection,while the difference between C2 levels [(921.55 ?431.31) vs (1 185.17?358.86)ng/ml) ] was significant.There was also no statistically significant between C0 levels of the recipients with side effects and those without side effects,but statistically significant difference was found between C2 levels [(1 302.59?450.21) vs (1 105.23? 371.64 )ng/ml].Analysis of the relationships between C2 levels and the incidences of acute rejection and side effects showed that no acute rejection and side effects rate of 4.3% were observed in the Neoral C2 interval from 1 250 ng/ml to 1 500 ng/ml. Conclusions Neoral C2 monitoring is a more sensitive predictor not only for acute rejection but also for side effect rate.The optimal C2 target level of Chinese renal transplantation recipients is 1 250 ～1 500 ng/ml for the first 3 months post transplantation.

Objective To observe the dynamic change of cytokines and effect of different stimulating combinations on dominant regulation, and describe the microenviroment character of local immune response. Methods PBMCs were separated from peripheral blood of healthy donors with density gradient centrifugation. The expression levels of cytokine genes under different stimulating combinations, including IL-2, IFN-?, IL-12, IL-4, IL-10 and TGF-?1, were detected by ELISA and RT-PCR. Results ELISA results indicated that secretion level of IL-2, IL-4, IL-12 and IFN-? were inhibited by IL-10. There were significant differences in IL-4 and IL-12 between control group and stimulating groups under the stimulation by anti-CD3 monoclonal antibody (McAb) or anti-CD3 McAb + anti-CD28 McAb combination. Significant differences in IL-2 only appeared in anti-CD3 antibody stimulating group. The concentrations of IFN-? were decreased moderately. At the mean time, IL-10 significantly promoted the secretion of TGF-?1 under the anti-CD3 McAb stimulation. There were similar results on the genes level for the studied cytokines. Conclusion The induction and maintenance of dominant regulation were dependent mainly on IL-10, which inhibits the overexpression of IL-4 and IL-12. It is the vital step for dominant regulation to avoid the mono-polarization development at the beginning of immune response.

Objective To investigate the effect of recipient dendritic cells (DC) loaded with donor-derived apoptotic cells on inducing murine cardiac allograft tolerance. Methods Apoptosis of donor-derived splenocytes (SC) was induced by ultraviolet B irradiation(UVB). UVB-irradiated allogenic SC were co-cultured with recipient bone marrow-derived DC that maturation was inhibited by NF-?B ODN Decoy, so that could acquire tolerogenic-immature DC loaded with donor-derived apoptotic cells (Decoy Apo-SC DC). A heterotopic vascularized heart transplantation was performed from BALB/c to C57BL/6 mice, and recipients were given one injection of recipient immature (Decoy Apo-SC DC) or mature (Apo-SC DC) DC engulfed donor-derived apoptotic cells (2?10 6 cells) through the portal vein at 7 days before the heart transplantation in the absence of immunosuppression. The cardiac survival and the expression of intragraft cytokines (IL-2, IL-10 and IFN-?) were evaluated.Results DC had potent phagocytosis of allogenic apoptotic SC (Apo-SC). NF-?B ODN Decoy inhibited engulfment of apoptotic cells-induced maturation of DC and then induced recipient tolerogenic DC. Recipient tolerogenic DC loaded with donor-derived apoptotic cells were able to cross-tolerate recipient T cells, which revealed by alloantigen-specific T-cell hyporesponsiveness in primary and secondary mixed leukocyte reaction. Injection of recipient tolerogenic DC loaded with Decoy Apo-SC DC through the portal vein at 7 days before the heart transplantation significantly prolonged vascularized heart allograft survival (MST 36.4 days versus 7 days in control group, P

The effect of HLA-DR matching was retrospectively examined at DNA level on rejection and graft survival of cadaver renal transplantation. HLA-DR matching was typed by PCR-SSP technique in 318 cyclosporine-treated primary cadaveric renal recipients. The recipients were divided into three groups:no DR mismatching (0MM), one DR mismatching (1MM) and two DR mismatching (2MM). The effect of genomic HLA-DR compatibility on early kidney function, acute rejection, steroid pulses and 1 year graft survival was retrospectively analyzed. HLA-DR alleles in all samples were successfully genotyped by PCR-SSP. The overall time of DNA typing was 4 hours. The patients well-matched(0MM),moderately-matched(1MM) and poorly-matched(2MM) were 11.6%, 51.9% and 36.5%, respectively. The total rejection rate, 1 year patient survival and graft survival in 318 recipients were 49.1%, 94.3% and 90.3%. Early graft function, acute rejection episodes, steroid pulses and graft survival in well-matched recipients were better than those in poorly-matched patients. In particular, significant difference was found in acute rejection episodes and 1 year graft survival,suggesting genomic compatibility of HLA-DR has effect on acute rejection and graft survival in cadaver kidney transplantation.

To investigate the antitumor effect of herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system on human bladder cancer cells (T24), a retroviral vector with the gene (pLXSN-TK) was transduced into the packaging cell line PA317. A nude mouse model with human T24 was established to examine the in vivo efficacy. The animals were randomly assigned to two treatment groups and two control groups. Treatment I and Treatment II were given in situ injection of virus suspension and PA317/TK respectively, followed by treatment with GCV for 14 days. Control I and Control II were given in situ injection of same volume of normal saline and PA317/TK respectively, followed by treatment with GCV and with normaly physiologic saline respectively for 14 days. The weight and the volume of tumor were measured. HSV-TK mRNA expression was determined by hybridization in situ. Cell apoptosis was evaluated by flow cytometry (FCM) and termininal deoxynucleofidyl transferase-mediated dUTP nick end labelling (TUNEL) technique. The results showed: (1) In vivo, the retrovirus transferred HSV-TK gene can be transduced into human bladder cancer cell T24. The tumors in T24 mice with TK gene transduced were much smaller than those in other groups. (2) After treatment with HSV-TK/GCV, the phenomenon of bladder ceancer cell apoptosis was more conspicuous as compared with that of other groups. Therefore, HSV-TK/GCV system can suppress the growth of T24 in vivo and may relate to "bystander effect". It could be a valuable therapy for human bladder cancer.
Animals ; Antiviral Agents ; therapeutic use ; Ganciclovir ; therapeutic use ; Gene Transfer Techniques ; Genetic Therapy ; Herpesvirus 1, Human ; enzymology ; genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Thymidine Kinase ; genetics ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms ; genetics ; pathology ; therapy