[Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice].

OBJECTIVE: To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice. METHODS: The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting. RESULTS: TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01). CONCLUSION: TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.

[Long-term survival of high-risk kidney transplant patients].

OBJECTIVE: To summarize the experiences in high-risk renal transplant recipients for ketter long-term survival. METHODS: From April 1991 to December 2008, a total of 921 kidney recipients with high-risk factors were divided into six groups as following: (1) pediatric patients (< 18 years old) (GI, n = 34); (2) retransplant recipients (GII, n = 169); (3) high sensitized patients (PRA> 30% or peak PRA > 50%)(GIII, n = 35); (4) elderly recipients (> 60 years old) (GIV, n = 297); (5) diabetic patients (GV, n = 112); (6) patients with HBV/HCV infection or HBV/HCV carrier (GVI, n = 274). Each group was compared to a control of 807 recipients without any above risk factor for patient and graft survival at 1, 3 and 5 years. Incidences of acute rejection (AR), chronic rejection (CR) and complication were analyzed and compared respectively between the studied subjects and the control group as well. RESULTS: Compared with the control group, patient/graft survivals were lower in GII, GIII and GVI (all P < 0.05), GIV had worse patient survival (P < 0.05); AR and CR incidences were greater in GI and GIII (all P < 0.05); GIV, GV and GVI had more complications. CONCLUSIONS: This study suggests the benefits for long-term outcome in high-immunological risk renal transplant recipients of low acute selection incidence rate, and reduction of complication incidences is the key to long term results for non-immunological high risk recipients.

[Multivariate analysis of the risk factors of cytomegalovirus pneumonia after renal transplantation].

OBJECTIVE: To identify the risk factors for cytomegalovirus (CMV) pneumonia after renal transplantation and investigate the early precaution measures. METHODS: A retrospective study was conducted in a group of 28 patients undergoing renal transplantation who were readmitted because of CMV pneumonia between Jan, 2005 and Dec, 2007. Chi-square test and multivariate logistic regression were used to identity the significant risk factors. RESULTS: Seven factors, namely recipient age, acute graft rejection, pre-transplantation dialysis, delayed graft function recovery, recipient peak PRA level, donor CMV positivity and the use of MMF were found to significantly correlate to post-transplant CMV pneumonia. Multivariate logistic regression further confirmed that donor CMV IgG positivity, acute graft rejection and pre-transplantation dialysis for over 6 months were independent factors to predict the occurrence of CMV pneumonia. CONCLUSIONS: Acute graft rejection control, appropriate donor selection and shortened dialysis before the transplantation can be crucial factors to reduce the incidence of CMV pneumonia after renal transplantation.

[Clinical study of pulmonary infection in kidney transplantation recipients taking new immunosuppressant].

OBJECTIVE: To explore the etiopathogenesis, therapy and incidence of pulmonary infection in kidney transplantation recipients taking new immunosuppressant. METHODS: The clinical data from 752 kidney transplant recipients were retrospectively analyzed, who were divided into 3 groups according to the immunosuppressants administered, namely group A (CsA+MMF+Pred, n=226), group B (FK506+MMF+Pred, n=386) and group C (FK506+Rap+Pred, n=140). The incidence and mortality of pulmonary infection were recorded and the analysis of etiopathogenesis, diagnosis and therapy of pulmonary infection were carried out in the 3 groups. RESULTS: Fifty-three patients acquired post-transplant pulmonary infection. The incidence of pulmonary infection was 7.08% (16/226) in group A, 7.25% (28/386) in group B and 6.43% (9/140) in group C. One patient died in group A and 2 in group B. Among the 53 patients, 24 had simple bacterial infection, 9 had cytomegalovirus infection, 1 had mycotic infection, 17 had combined infection, and 2 had unidentified pathogen infection. Of the pathogenic bacteria detected, 68.35% were Gram-negative. CONCLUSION: Gram-negative bacteria are most likely responsible for pulmonary infection after kidney transplantation, which most possibly occurs within 6 months after kidney transplantation. Early diagnosis and early treatment are critical for decreasing the mortality of severe pneumonia and for improving the survival rate of the patients and grafts.

[Effect of trichostatin A on proliferation and interleukin-2 expression of mouse T cells in mixed lymphocyte culture].

OBJECTIVE: To investigate the effect of trichostatin A (TSA) on proliferation and interleukin-2 (IL-2) expression of mouse T cells in mixed lymphocyte culture (MLC), and explore its effect on T cell-mediated immune response. METHODS: BALB/c and C57BL mouse MLC was treated with different concentrations of TSA for different durations, and the lymphocyte inhibition ratio was measured by MTT assay. With CTX as the control, one-way MLC system of BALB/c and C57BL mouse was treated with the same concentrations of TSA, and IL-2 expression in the T cells was observed by flow cytometry. RESULTS: TSA inhibited the proliferation of T cells in the MLC in a time- and dose-dependent fashion. It also reduced the IL-2 expression in one-way MLC dose-dependently, showing it significantly differed from the effect of CTX (P<0.01). CONCLUSION: Histone deacetylase inhibitor TSA can inhibit the proliferation and reduce IL-2 expression of the T cells in MLC of mice, and therefore inhibit the T cell-mediated immune response.

[Application of mycophenolate mofetil in hepatitis C patients after kidney transplantation].

OBJECTIVE: To discuss adequate application of mycophenolate mofetil (MMF) in hepatitis C patients after kidney transplantation. METHOD: A one-year follow-up study was conducted in 49 patients with hepatitis C but normal liver function before kidney transplantation, who were given postoperatively immunosuppressants of predisone, MMF and CsA/FK506. Patients with abnormal liver function after kidney transplantation who continued MMF therapy at routine dose and those with reduced or suspended MMF therapy all received intravenous therapy for liver protection, and the duration of therapies was recorded. RESULTS: Nineteen patients presented with abnormal liver function after operation, and the duration of abnormal liver function till recovery was 32.82-/+4.13 days in the patients with unsuspended MMF therapy and 13.31-/+2.98 days in those with reduced or suspended MMF (P<0.05); the former patients required subsequently 62.7-/+3.23 days to recover normal liver function and the latter need only 23.4-/+2.29 days (P<0.05). CONCLUSION: MMF should be reduced or suspended when liver function abnormality occurred in patients with hepatitis C after kidney transplantation, and immediate intravenous therapy for liver protection may prove beneficial.

[Clinical observation on long-term surviving patients after combined abdominal organ transplantation].

OBJECTIVE: To summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation. METHODS: From October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation. RESULTS: All of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months. CONCLUSIONS: Combined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.

[Simultaneous liver-pancreas-duodenum transplantation: one case report and review of the literature].

OBJECTIVE: To investigate the effect of treatment on end-stage liver disease and type-I diabetes mellitus with simultaneous liver-pancreas-duodenum transplantation. METHOD: In September 2003, one patient with chronic hepatitis B, liver cirrhosis, hepatic cellular cancer, and insulin-dependent diabetes received simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation. Liver and pancreas graft function was monitored after transplantation. RESULTS: The function of pancreas allograft was recovered immediately and the patient became insulin-independence postoperatively. The liver allograft was experienced an acute rejection episode and reversed by intravenous bolus methylprednisolone. The recipient was currently liver disease-free and insulin-free more than 21 months. CONCLUSIONS: The simultaneous liver-pancreas-duodenum transplantation is an effective method in the treatment of end-stage liver disease and type-I diabetes mellitus.

[Perioperative management of multiorgan transplantation].

OBJECTIVE: To summarize the experience with perioperative management of multiorgan transplantation. METHODS: From October 2001 to January 2005, 19 patients received multiorgan transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The surgical techniques, application of immunosuppressants, and complication management were reviewed. RESULTS: All transplantation procedures were performed successfully. The transplantation-related complications included tacrolimus-induced renal toxicosis in 1 (5.3%) case, acute graft rejection in 3 (15.8%) cases, intestinal hemorrhage in 2 (10.5%) cases, intra-abdominal hemorrhage in 1 (5.3%) case, and lung infection in 1 (5.3%) case, all of which were cured after proper treatment. CONCLUSIONS: Donor selection, good quality of the donor organ, proper surgical approaches, adequate use of the-mmunosuppressants, and prevention of complications are essential to the success of multiorgan transplantation.

[Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation in a diabetic patient with end-stage liver disease].

OBJECTIVE: To study the effect of combined transplantation of the liver and the pancreas in diabetic patients with end-stage liver disease, and explore the optimal surgical procedure. METHODS: Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations were performed in a patient diagnosed as having chronic hepatitis B, hepatocirrhosis, hepatic cellular cancer, and insulin-dependent diabetes. Immunosuppression therapy utilized prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and simulect. The function of the liver graft, serum amylase and lipase, blood glucose, and C-peptide were monitored after transplantation. RESULTS: Insulin was withdrawn at the 6th day after operation, good liver allograft functional recovery was achieved, without such complications as pancreatitis, thrombosis, and localized infections. CONCLUSION: End-stage liver disease with concomitant insulin-dependent diabetes is the indication for combined liver-pancreas transplantations, for which simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations may constitute the optimal surgical approaches as the primary choice.