ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation.Methods.Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean±SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7±3.9 and 13.4±2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5±15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids.Results.Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups.Conclusions.We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Glutamine (gln)-supplemented University of Wisconsin (UW) solution improves overall small bowel (SB) preservation. Sustained gln metabolism in a system devoid of hepatic detoxification will necessarily result in the accumulation of pH active end products leading to nonphysiologic pH shifts. We hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane sulfonic acid (BES), a known buffering agent, would potentiate the beneficial effect of gln supplementation by addressing the fundamental metabolic principle of pH homeostasis.Methods.Sprague-Dawley SB rats were administered a vascular flush with one of four solutions: UW; UW+90 mM BES (UWB); UW+2% gln (UWG); or UW+2% gln+90 mM BES (UWBG). Indices of energetics, barrier function, gln catabolism, and histology (light and electron microscopy) were assessed over a 10-hr cold storage time course.Results.Superior gln utilization in the UWBG group was indicated by elevated levels of key catabolites (glutamate, aspartate, glycine, ammonia). The addition of BES and gln resulted in significantly higher levels of all energetic parameters (ATP, total adenylates) at 10 hr compared with UW, UWB, and/or UWG. Barrier function was markedly improved after 10 hr storage in the UWBG group; mannitol permeability was 169 nmol/cm2/hr versus 572 and 445 nmol/cm2/hr (for UW and UWG, respectively). Histologic injury at 10 hr was 5.5, 7.5, and 8 (Park’s grade) for UWBG, UWG, and UW. Ultrastructural damage was markedly reduced with UWBG, as assessed by grade of mitochondria damage.Conclusion.This study strongly supports that the beneficial effects of gln-enriched UW solution can be amplified when combined with an effective buffering agent such as BES.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Previous studies have implicated the allogeneic immune response in the development of obliterative bronchiolitis after lung transplantation. However, the progression of specific pathogenic events leading to this form of chronic allograft dysfunction have not been well characterized. We used a murine tracheal transplantation model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4+T cells to show that obliterative airway disease (OAD) that developed in these allografts was preceded by indirect recognition of the HLA-A2 molecule and subsequent development of anti-HLA-A2 antibodies.Methods.Tracheas from HLA-A2+C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Allograft histopathology as well as anti-HLA-A2 T-cell proliferative responses and anti-HLA-A2 antibody development were determined at days 5, 10, 20, and 28 after transplantation.Results.All of the HLA-A2+tracheal allografts transplanted into C57BL/6 recipients demonstrated complete development of OAD by day 20. Spleen cells from the mice that underwent transplantation demonstrated significant proliferation against HLA-A2+cells by day 5. Indirect recognition of HLA-A2-derived peptides by spleen cells from allograft recipients was also higher on days 5 and 10 as compared with irrelevant peptides derived from HLA-A1, HLA-A3, and HLA-B44. Allograft recipients showed detectable levels of anti-HLA-A2 antibodies by day 5 and full development of anti-HLA-A2 antibodies by day 20.Conclusion.These results show that sensitization of CD4+T cells against the mismatched HLA-A2 alloantigen precedes the development of anti-HLA antibodies as well as OAD, suggesting an important role for alloreactive CD4+T-cell activation and alloantibody development in the immunopathogenesis of OAD.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.In pig-to-human discordant xenotransplantation, the xenograft can be rejected by a formidable human xenogenic T-cell response, even if the graft has gone through hyperacute rejection or delayed xenograft rejection (acute vascular rejection). We therefore examined, in this study, whether the human-to-pig cellular response could be attenuated through the generation of a transgenic pig for human HLA II.Methods.With the technique of microinjection, we produced the HLA DPw0401 transgenic pig. The expression of the HLA DPw0401 gene on peripheral blood mononuclear cells (PBMCs) of the transgenic pig was examined by reverse transcriptase-polymerase chain reaction and flow cytometry. The antigenicity of the transgenic HLA DPw0401 molecule was tested by the HLA DPw0401-primed lymphocyte test reagent. The cellular response was analyzed by xenogenic mixed lymphocyte culture.Results.The mRNA and protein of HLA DPw0401 were expressed in the PBMCs of the transgenic pig. The PBMCs of the HLA transgenic pig induced a stronger cellular reaction to HLA DPw0401-primed lymphocyte test reagents than the nontransgenic littermate pig (n=7,P<0.01). In direct xenogenic mixed lymphocyte culture with responders from HLA DPw0401(+) humans, the PBMCs from the HLA DPw0401 transgenic pig, as compared with those from the normal pig, induced a lower degree of xenogenic cellular response to human PBMCs (n=4,P=0.08).Conclusions.Our preliminary data demonstrated the possibility that the human HLA DPw0401 phenotype can be transferred onto porcine cells through the generation of HLA transgenic pigs and make the PBMCs of humans more tolerant to porcine cells.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Although the value of duodenal histology as a means to diagnose acute rejection in pancreaticoduodenal allografts has been validated, it is not known how the duodenum responds to antirejection treatment in comparison with the pancreas.Methods.Diabetic Lewis rats received a pancreaticoduodenal allograft. Cyclosporine was given for 5 days and then discontinued for 2 days (group 1), for 4 days (group 2), for 6 days (group 3), for 8 days (group 4), for 9 days (group 5), and for 10 days (group 6). Two animals of each group were killed for histology at the end of immunosuppressive-free intervals. In the remaining rats, rejection was treated with methylprednisolone on 3 consecutive days. Duodenal histology was compared with pancreatic morphology before and after treatment of rejection.Results.Duodenal histology had a positive and negative predictive value of 100% for detection of acute rejection in the pancreatic portion of the graft. After antirejection treatment, duodenal morphology was however less accurate (positive predictive value, 96%; negative predictive value, 67%). The Spearman correlation coefficient (p) of duodenal and pancreatic rejection grades was higher before antirejection treatment (p=1.0) than thereafter (p=0.724). Considering interstitial and vascular changes separately, vascular rejection correlated to a higher extent than interstitial rejection between the two portions of the graft (p=0.725 vs.p=0.677).Conclusions.Duodenal histology accurately predicts the initial diagnosis of rejection of the pancreas. However, after treatment of acute rejection, duodenal morphology is more likely to recover from rejection than the pancreas. Awareness of this phenomenon might be important for the interpretation of duodenal follow-up biopsies.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.The anhepatic pig model was used to evaluate a bioartificial liver developed in our institution (AMC-BAL). The bioartificial liver is based on oxygenated plasma perfusion of porcine hepatocytes attached to a polyester matrix.Methods.Pigs (n=15) underwent total hepatectomy with restoration of caval continuity using a polyethylene, three-way prosthesis. In group I, pigs received limited intensive care under continuation of general anesthesia (n=5). Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II and III were connected to the extracorporeal system 24 hr after hepatectomy, for a period of 24 hr. The main outcome parameters were as follows: survival time, liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood ammonia, and total/direct bilirubin.Results.Survival (mean ± SD) of the anhepatic pigs was significantly increased in the BAL-treated group (group III: 65±15 hr), as compared with the control groups (group I: 46±6 hr and group II: 43±14 hr). Mean blood ammonia levels during BAL treatment were significantly lower in the BAL-treated group in comparison with both control groups (P=0.02). Total and direct bilirubin levels gradually increased after hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl, respectively, showing no differences between the three groups.Conclusions.(1) Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes significantly increases survival time, which is associated with a significant decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct bilirubin levels as a result of extrahepatic bilirubin conjugation.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Recent studies have shown that head-neck draining lymph nodes (DLN) are required for priming the immune response during corneal allograft rejection. In this study we have investigated further the role of the DLN and spleen in corneal graft rejection in mice.Methods.Individual DLN (submandibular [SM]; superficial cervical [SC]; and internal jugular) or their combinations were removed in mice undergoing corneal allografting (C57BL/10, H2bto BALB/c, H2d). In some mice, DLN from syngeneic mice were retransplanted, whereas other mice underwent removal of the spleen before corneal allografting. In a high-risk group of mice, removal of the DLN before a second corneal graft procedure was performed.Results and Conclusions.The data show that a single specific lymph node, i.e., the SM node, is the major DLN involved in corneal graft rejection whereas its nearest neighbor, the SC DLN, not only cannot substitute for the SM node in priming the immune response but may be involved with the spleen in immune privilege. Retransplantation studies of syngeneic LN indicate that the site of the DLN is more important to the process of graft rejection than the specific DLN tissue. This applies to the DLN whether it contains naive or memory allospecific T cells as shown in experiments in which removal of the SM DLN from mice who had already been primed by a previous corneal graft, prevented rejection of a second corneal graft in the same strain combination.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID