ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The purpose of these studies was to determine whether free radicals were formed as a consequence of reperfusion during orthotopic liver transplantation and whether their formation was related to graft failure. Grafts were stored for 18 hr in Euro-Collins solution or for 48 hr in University of Wisconsin solution (nonsurvival conditions) and reperfused with blood containing the spin trap α-phenylN-tert-butylnitrone (PBN). Venous blood samples (4–5 ml) were collected, and serum was extracted with chloroform and methanol (2:1) and analyzed for radical adducts by electron paramagnetic resonance (EPR) spectroscopy. In samples from livers stored under nonsurvival conditions, EPR spectra were detected indicating the presence of PBN radical adducts. In contrast, radical adduct formation was 3− to 4-fold lower in similar experiments performed with untransplanted livers or with livers stored under survival conditions (1 hr in Ringer's solution or 24 hr in UW solution). Oxygen radicals are most likely involved in the production of radical adducts because formation was nearly completely prevented by superoxide dismutase plus catalase or Carolina rinse, which contains glutathione, desferrioxamine mesylate, and allopurinol. Radical adduct formation was much greater in a blood-free perfusion system where oxygen delivery was high, suggesting that blood elements are not necessary for radical adduct formation. An inverse correlation between survival of livers stored in UW solution and radical adduct signal was observed in this study. Thus, it is concluded that free radicals formed during reperfusion are involved in the mechanism of graft failure following liver transplantation in the rat.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The optimal timing of administration of free radical scavengers in lung preservation has yet to be determined. In previous studies, the oxygen free radical scavenger dimethylthiourea (DMTU) has improved pulmonary function when added to Eurocollins flush solution at the time of lung harvest and infused at the time of lung reimplantation. To determine when DMTU must be administered in order to preserve lung function most effectively, 16 dogs underwent lung allotransplantation. Donor lungs were flushed with modified Eurocollins solution (50 ml/kg) and stored for 12 hr at 4°C. DMTU was either added to the flush solution (5 g) or infused (20 g over 2 hr) at the time of reimplantation. Investigators were blinded to the time of DMTU administration. The contralateral pulmonary artery was ligated after a 1-hr stabilization period. Measurements were recorded for 8 hr while keeping FiO2constant at 40%. The flush group demonstrated significantly improved survival and oxygenation compared with the infusion group. The mortality rate was 50% in the infusion treatment group, while no deaths occurred in the flush animals. Lung function is adequately preserved after 12-hr storage when DMTU is administered in the flush solution at the time of harvest. It would appear that oxygen free radical scavengers must be present in lung tissue during storage in order to be effective.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study was undertaken to assess the metabolic effect of fetal and adult hepatocyte transplantation in the Gunn rat, genetically incapable of bilirubin conjugation. A comparison was made between fetal and adult hepatocytes transplanted into the spleen, and those injected into polytetrafluoroethylene (PTFE) solid supports that had previously been implanted intraperitoneally. Between 4 and 12 weeks after intrasplenic transplantation of adult liver cells, serum bilirubin was significantly decreased when compared with control animals (39.6±5.6%;P<0.01 vs. controls). Intrasplenic transplantation of fetal hepatocytes resulted in a maximal decrease of 33.2±9.1% at 8 weeks postoperatively (P<0.02 vs. controls). Similar declines of serum bilirubin levels were found after transplantation of adult or fetal liver cells into the solid supports. At 12 weeks after transplantation, bilirubin conjugates were detectable in the bile of all animals that underwent intrasplenic hepatocyte transplantation and in 60% of those that underwent the solid support procedure, whereas none could be detected in control animals. Histological evidence of surviving cells was obtained in all but one animal at 12 weeks, and confirmed at 12 months postoperatively. It is concluded that the PTFE solid support technique offers an attractive alternative to the intrasplenic route, and that both fetal and adult hepatocytes, transplanted in either way still exert their conjugating activity after 12 weeks.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of total-body irradiation of the donor on hepatic allograft survival was studied in the rat, with ACI(RT1a) as the donor and LEW(RT1) as the recipient. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of only 10.2±0.3 days. The doses of irradiation were 450, 750, and 1000 rads administered 24 hr prior to harvesting or subsequent transplantation. TBI with a dose of 750 rads significantly prolonged the survival of the hepatic allograft to 30.3±1.7 days, without concomitant immunosuppression. However, neither 450 rads nor 1000 rads of TBI resulted in successful suppression of graft rejection. TBI appeared to have a beneficial effect on hepatic allograft survival and to have no deleterious effect on isograft survival, suggesting a possible modulation of the immunogenicity of the donor organ. Although the cause of this beneficial effect is not clear, TBI with a dose of 750 rads 24 hr prior to organ harvest seems to be optimal to eliminate-antigen presenting cells in the donor organs.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Congenic LEW.1W(RT1.u) heart grafts in LEW.1A(RT1.a) recipient rats are rejected in 15±6 days. Tolerance (>100 days) can be induced by pretransplant donor-specific blood transfusion. In this case, the graft is not rejected, although it is infiltrated by mononuclear cells specifically cytotoxic, in vitro, against allogeneic donor splenocytes. We studied the expression of MHC class I and class II antigens, IFN-γ, and IL-2 mRNA in the rejected and tolerated grafts by Northern blotting and in situ hybridization. Our data show that both class I and class II mRNA accumulate in both types of graft, and that class I mRNA accumulation occurs more rapidly in the tolerated grafts. IFN-γ and IL-2 mRNA accumulate to lower levels and with delayed kinetics in the tolerated grafts compared with the rejected ones, suggesting a role for these lymphokines in the mechanism of rejection/tolerance in this model. This hypothesis is also supported by the observation that IFN-γ treatment abrogates the induction of tolerance in the recipients receiving pretransplant donor blood transfusion. Furthermore, we observed an uncoupling of the accumulation of IFN-γ mRNA and of MHC class I and class II mRNA. Our data confirm that the mechanisms of tolerance in this model depend, in part, on alterations of the IL-2/IL-2R pathway of lymphocyte activation but also clearly indicate a decrease of IFN-γ mRNA accumulation, suggesting that the defect involves several activation molecules.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In order to study their effects on the bile secretion, cyclosporine and methylprednisolone were injected intravenously into rats at a dose of 10 mg/kg b.w. for 30 min. Methylprednisolone had no effect on bile secretion. Cyclosporine led to transient intrahepatic cholestasis characterized by decreased bile flow as well as a decrease of bile salts and cholesterol in bile. Phospholipid levels were not affected. Liver biopsy showed no particular anomaly. These findings suggest that the observed cholestatic reaction may be due to impairment of the metabolism of cholesterol into bile salts or of the conjugation of bile salts rather than to disturbances in bile secretion. After liver transplantation in humans, cholestasis associated with acute rejection or nonspecific cholestasis cannot be attributed directly to the effect of cyclosporine. Cholestasis can be offset by administering taurocholate at a dose of 10 μmol;/min/kg b.w. in order to maintain bile salt and phospholipid levels high enough to ensure proper “vectorization” of cholesterol to bile.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children <18 years of age were registered in the study. The ages of the donors were ≤5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and ≥40 years in 108.The risk of graft loss was related to donor age by a proportional hazards analysis. The ideal donor age was 20–25 years. The risk of graft loss was increased by both young and old donor age. The risk of graft loss from a neonate donor was 2.7-fold that of the ideal donor, and the risk from a 50-year-old donor was 1.8-fold that of the ideal donor. The relationship between donor age and graft survival was not affected by the age of the recipient. Cold storage time had an added impact on graft survival: grafts with cold storage time >24 hr were 1.5 times more likely to fail than grafts with shorter cold storage time for all donor ages. Analysis of the causes of graft failure revealed that 9.9% of grafts from donors ≤5 years of age were lost due to vascular thrombosis, primary nonfunction, and other technical causes, compared with 4.6% in 6–9, 4.4% in 10–39, and 2.8% in ≥40-year-old donors.We conclude that kidneys from both young and old donors are at increased risk for graft loss, and this increased risk is seen in all recipient age groups. Many of the losses from the young donors—but not older donors—may be due to technical causes. Knowledge of these risks can be used to develop strategies for optimal utilization of kidneys from young and old donors.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to investigate the influence of HLA-DR antigen “splits” at the DRB1 gene level on the incidence of acute graft rejection in the renal transplant.For all patients, the incidence of acute rejection was proportional to the number of the serological HLA mismatch (0% in patients with two-haplotype match; 18% with HLA-A, -B, and -DR zero mismatch; 33% with HLA-DR zero mismatch; and 48% with HLA-DR one mismatch). For the patients with serological HLA-DR zero mismatch, the incidence of acute rejection in patients with HLA-DRB1 one mismatch (10/13: 77%) was significantly higher than that in those with zero mismatch (2/27: 7%).It was concluded that genotyping for HLA-DRB1 alleles would be beneficial in predicting acute rejection in patients with serological HLA-DR zero mismatch, although no difference was noted in the graft survivals.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Proliferative responses to nonspecific mitogens were analyzed for 119 bronchoalveolar lavages and 108 concurrent peripheral blood samples from 35 lung transplant patients. The patients were classified at each time as normal, rejecting, or infected on the basis of trans-bronchial biopsy, culture results, clinical signs, and pulmonary function. During rejection episodes the bronchoalveolar lavage responses to concanavalin A and phytohemagglutinin were significantly increased (P<0.004 andP<0.006, respectively). The differences were less pronounced when rejection occurred within 30 days after bolus immunosuppressive therapy, either as immunoprophylaxis or as treatment for a previous rejection episode, and were not significantly different from normal. Differences in response during rejection were limited to the graft; analysis of circulating T cells was not helpful (P=NS).In contrast, markedly depressed responses to Con A and PHA were seen during infection. Significant differences were observed both in the graft (P<0.007) and in circulating lymphocytes (P<0.02), suggesting that global depression of mitogen response is associated with immunocompromise. Sequential analysis of 6 patients showed that individual changes in mitogen response paralleled those seen in the population (P<0.046, normal vs. rejection andP<0.043 normal).These findings suggest that mitogen assays of bronchoalveolar lavage lymphocytes and, to a lesser extent, PBL, are clinically useful in assessing intragraft immunocompetence and in distinguishing rejection from infection in lung transplant patients.

ISSN:0041-1337    

出版商:OVID    

年代:1992

数据来源: OVID