摘要:

The CD26 antigen, one of the major costimulatory molecules in T cell activation, was shown to possess dipeptidyl peptidase IV (DPP IV) activity. Previously, we demonstrated that immunosuppressed kidney transplant patients exhibit lower DPP IV serum activity as compared with healthy individuals. In the present study, we analyzed the role of CD26/DPP IV in the immune cascade triggered by organ transplantation and leading to acute rejection of cardiac allografts in rat recipients. Transplantation of hearts from (Lewis × Brown Norway)F1donors into Lewis hosts resulted in an early (24 hr) increase in cellular CD26 expression, followed by a rise in DPP IV serum activity, which peaked at day 6, i.e., before the time of actual graft loss. Specific targeting of DPP IV activity with a novel, low-molecular-weight inhibitor of the diphenyl-phosphonate group (prodipine) abrogated acute rejection and prolonged cardiac allograft survival to 14.0±0.9 days (P<0.0001). Prodipine treatment prevented the early peak of cellular CD26 expression and thoroughly suppressed systemic DPP IV activity. The inhibition of DPP IV was associated with severely impaired host cytotoxic T lymphocyte responses in vitro. These results demonstrate the role of CD26/DPP IV in alloantigen-mediated immune regulation in vivo and provide the first direct evidence that CD26/DPP IV plays an important role in the mechanism of allograft rejection. The model of targeting CD26/DPP IV may reveal essential interactions on the level of costimulatory alternate T cell activation pathways, allowing a more subtle approach for more selective immunosuppression in transplant recipients.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a critical role in initiating and maintaining immunogenic inflammation. We performed a series of experiments to determine whether the topical application of IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the murine model of orthotopic allotransplantation.Methods.For all experiments, C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor histocompatibility-disparate) eyes. “High-risk” transplants were transplants that had been sutured into BALB/c recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 2 weeks earlier. Both risk groups were divided in a masked fashion into treatment subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were evaluated for 8 weeks after surgery for signs of rejection. At the end of follow-up, corneal specimens were processed for enumeration of Langerhans cells and histopathological evaluation.Results.Survival rates of both normal-risk and high-risk transplants increased significantly among the IL-1ra-treated animals compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and Kaplan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk IL-1ra-treated grafts had significantly less inflammation and Langerhans cells infiltration compared with untreated controls.Conclusions.Topical treatment with IL-1ra has a significantly positive effect in promoting corneal allograft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The significance of noninvasive techniques to the early diagnosis of acute rejection in kidney transplants remains elusive. In this study, we examined whether an early posttransplant increase in serum- and urine-soluble interleukin (IL) 2 receptor (sIL-2R) and IL-6 levels predicted acute rejection.Methods.Sequential determinations of serum and urine sIL-2R and IL-6 were performed in the first 30 postoperative days in 40 renal transplant patients. Changes during the posttransplant period observed in 26 patients who had one or more episodes of acute rejection (group A) were compared with those recorded in 14 patients who did not experience acute rejection of their graft (group B).Results.Serum sIL-2R was higher than normal in patients of groups A and B without statistical differences between the two groups. In the first 3 days after transplantation, urinary sIL-2R was higher than normal in group A but not in group B. Urinary sIL-2R at days 2 and 3 was significantly higher (P<0.05) in group A than in group B. In the first 5 days after transplantation, urinary IL-6 was persistently higher than normal in group A, whereas it progressively decreased to normal value on day 4 in group B. Sudden increases (doubling within 24 hr) in urine IL-6 preceded clinical diagnosis of acute rejection by a mean period of 2 days, with an 87% sensitivity and a 64% specificity, and also predicted recurrent rejection episodes.Conclusions.Sequential monitoring of urinary sIL-2R and IL-6 levels does allow very early diagnosis of rejection without invasive procedures. Specifically, high urinary sIL-2R in the first 5 posttransplant days identifies the subgroup of patients at risk. In the subsequent days, a sudden increase in urinary IL-6 occurs in those of the above patients who will indeed reject their graft.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Pretransplant blood transfusion can have a favorable effect on renal and cardiac graft survival. In a previous study, we found that HLA-DR-shared blood transfusions led to better graft survival after kidney transplantation. In the present study, we tried to confirm and extend these findings by analyzing the effects of blood transfusion on the clinical course following heart transplantation. According to a predefined protocol, cardiac allograft recipients received random blood transfusion before surgery. A beneficial effect of HLA-DR-shared blood transfusion could be observed on survival and on the number of rejection episodes. Patients who had received an HLA-mismatched transfusion had significantly more infections, and in this group, more patients died due to malignancies. To study a possible role of immunomodulating T cells, patients who had or had not received prophylactic anti-T cell therapy were analyzed separately. In both groups, a beneficial effect of HLA-DR-shared blood transfusion could be demonstrated. These results indicate that the administration of HLA-DR-matched blood transfusion before transplantation is beneficial in cardiac allograft recipients, and that regulatory T cells are either not directly involved or (partly) resistant to modulation by anti-T cell antibody therapy.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Veno-occlusive disease of the liver is a serious and often life-threatening complication after bone marrow transplantation. Although risk factors for the development of veno-occlusive disease have been postulated, there is no precise method for accurately identifying those patients who are at risk and for whom early intervention and treatment would have maximum potential benefit. Liver transplantation has been advocated as a treatment for veno-occlusive disease in selected patients.Methods.In this report, we describe a patient who underwent liver transplantation for life-threatening veno-occlusive disease after autologous bone marrow transplantation for acute lymphoblastic leukemia.Results.Liver engraftment was achieved, but the patient developed Pneumocystis pneumonia, which failed to respond to pentamidine. The patient died 6 months after liver transplantation.Conclusions.While acknowledging the limited experience of orthotropic liver transplantation in this patient population, we suggest its consideration as a feasible, potentially beneficial treatment option in patients with severe veno-occlusive disease after bone marrow transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The feasibility of adult-to-adult living donor liver transplantation (LDLT) is restricted by the adequacy of the graft size. A left lobe graft from a relatively small donor will not meet the metabolic demand of a larger recipient. We report a successful LDLT performed on a 90-kg man using an extended right lobe graft weighing 910 g from his relatively smaller-size brother. The donor-to-recipient body weight ratio was only 0.82. No homologous blood transfusion was required for the donor, and the donor recovered uneventfully except for mild transient hyperbilirubinemia. The graft provided adequate function for the metabolic needs of the recipient despite postoperative septic complications. Both donor and recipient were well with normal liver function at 4 months after operation. LDLT using the extended right lobe liver graft can extend the limit on the size of the adult recipient and may be a viable option even when the donor is relatively small compared with the recipient.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Failed renal allografts are sometimes left in situ for additional clearance and urine production during hemodialysis or peritoneal dialysis, and low-dose immunosuppressive medication is often continued in such patients. We compared the morbidity and mortality due to infections between patients with (group A) or without (group B) low-dose immunosuppression (i.e., transplantectomy).Methods.In a hospital-based cohort study, we analyzed data from patient files. We evaluated 37 patients who received 42 kidney transplantations between May 1975 and November 1995.Results.A total of 2.28 vs. 0.68 infections/patient-year were found in groups A and B, respectively. The odds ratio of one or two infections developing for patients in group A compared with group B was 14.2 (95% confidence interval, 1.4-143.4;P<0.025) and 4.3 (95% confidence interval, 1.1-17.3;P<0.04). A total of five lethal infections were found in group A; no lethal infections were found in group B.Conclusions.The increase in serious and life-threatening infections associated with even low-dose immunosuppression argues in favor of discontinuation of these drugs. The removal of failed renal allografts should be considered.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A 12-year-old girl affected by idiopathic dilated cardiomyopathy and renal failure was referred to our institution for cardiac transplantation. A simultaneous heart-kidney transplantation from the same donor was decided. The immunosuppression schedule consisted of azathioprine, antithymocyte globulin, steroids, and cyclosporine. At a follow-up visit at 24 months after transplantation, no episodes of heart or kidney rejection had occurred and cardiac and renal function were good. Concomitant failure of heart and kidney is well known in the literature, but it appears to be more frequent in adult as compared with the pediatric population. This is the first case of combined heart and kidney transplantation in a child. Because of the successful outcome and good follow-up, the number of combined organ transplantations will most likely increase in the future.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We report the case of a lung transplant recipient with progressive cytomegalovirus (CMV) disease due to a resistant CMV strain emerging under ganciclovir (GCV) therapy. A discriminative polymerase chain reaction (PCR) assay, designed to detect the resistance-related V460 mutation within the viral enzyme UL97, revealed the presence of a mutated strain in a heterogeneous isolate 51 days after transplantation. The conventional antiviral susceptibility assay had failed to demonstrate resistance to GCV. Under prolonged GCV therapy, the mutated strain dominated the wild-type strain, as shown by the PCR assay. This domination led to laboratory resistance, associated with recurrent fever and progressively severe retinitis. As this discriminative PCR assay was shown to be effective in detecting mutated strains that constitute a minority in the virus load, it should allow better management of patients with CMV disease.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The present study concerns the influence of acinar contamination on pancreatic islets encapsulated in an artificial membrane (AN 69).Methods.Pure, handpicked pancreatic islets were contaminated by the addition of acinar tissue (ratio, 1:1). The morphological aspect and insulin release of both pure (n=12) and contaminated (n=12) encapsulated islets were assessed after 10 days of culture or implantation in the peritoneal cavity of rats.Results.After implantation, the encapsulated islets, irrespective of their purity, were totally altered, whereas the morphological aspect of the cultivated islets remained intact only in the absence of acinar tissue contamination. This contamination induced a significant decrease in the stimulation index of insulin release. The stimulation index decreased by 42% for fresh islets and by 52% and 34% for cultivated and implanted islets, respectively, without modification in their basal release of insulin.Conclusions.The acinar tissue proved detrimental to the encapsulated implanted and cultivated islets.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID