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Biomedical subjects

M F Mozes

Publications and source records attributed to M F Mozes.

At least 19 recordsLinked to original sources
PubMed1995

Cytotoxic T-cell role in renal allograft rejection and regulation. Renal allograft infiltrating cytotoxic T-cell line with suppressor-inducer function.

We previously investigated the characteristics of renal allograft infiltrating T-cell lines that were propagated from biopsy and nephrectomy specimens designated as IG-Bip and IG-Neph, respectively, or analogous line designated IG-T-eff, which was generated by co-culturing pretransplant recipient blood with irradiated donor splenocytes (manuscript submitted). The recipient (IG) had no previous sensitization to donor mismatched HLA antigens (A2 and DR1). Phenotypically, all lines were of recipient origin and were CD3+, TCR alpha beta +, DR+. However IG-Bip line was low in CD4 (19%) and high in CD8 (50%), whereas IG-Neph and IG-T-eff lines had equal mixture of CD4+ (34%) and CD8+ (38%) subsets). Functionally, all three lines contained donor-specific CTLs. In the present report, we used the in vitro MLR to examine the possible utilization of these CTL lines as inducer cells to generate donor-specific Ts cells from recipient PBLs. Coculturing IG-PBL that was drawn before or after transplantation and immunosuppression with irradiated IG-T-eff or IG-Neph but not IG-Bip CTL lines, generated Ts cells. Ts cells were of recipient origin and were CD3+, CD8+, leu 11b+, CD28-, all characteristic of Ts-effector phenotype. Ts cells inhibited MLR response of recipient PBLs against donor or third-party stimulators that shared with the donor the mismatched HLA antigens. Ts suppression was more pronounced against early phase of MLR response and was not due to a shift in MLR kinetics or nonspecific soluble suppressor or cytotoxic products. These findings suggest that allograft infiltrating CTLs or their in vitro generated analogous line may modulate allograft rejection by acting as Ts inducers and that Ts induction was dependent on the presence of the CD4 subset within the Ts-inducer cells but was not dependent on renal transplantation or immunosuppression.

Cell Line↗
PubMed1992

A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction.

Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of a PGE-1 analogue on the survival of cardiac transplant rats.

Prostaglandins can be considered as soluble factors of cell-mediated immunity. Studies with animal models have shown that prostaglandins of the series E-1 (PGE-1) can modulate the lymphocyte response to alloantigens. The goal of this work was to evaluate the immunosuppressive effect of a PGE-1 analogue (Enisoprost) on cardiac allograft survival in rats. PGE-1 was given to groups of six rats with heterotopic cardiac transplant. Group 1 was the untreated control group. Group 2a received PGE-1 from 0 to 4 days after transplant and group 2b received PGE-1 from 7 days before transplant to 4 days after transplant. Group 3 was treated with donor-specific blood transfusions (DST) 7 days before transplant. Groups 4a, 4b, and 4c were treated with DST and PGE-1 (0 to 4 days, -7 to 0 days, and -7 to 4 days relative to transplant, respectively). Group 5 was treated with cyclosporine (CsA), groups 6a, 6b, and 6c received DST, CsA and PGE-1. Cardiac allograft survival of group 2a (PGE-1) was better than that of the control group (9.6 +/- 1.7 days vs. 6.6 +/- 1.9 days) X +/- SD; p < 0.05. Group 4a (DST+PGE-1) had better cardiac allograft survival than group 3 (DST) (20.0 +/- 14.3 days vs. 14.3 +/- 3.3 days, respectively; p < 0.05). Group 6a (DST+CsA+PGE-1) had a better graft survival than group 5 (CsA) but the difference was not significant (44.6 +/- 13 days vs. 37.5 +/- 19.5 days, respectively; p = 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1991

Digoxin-like immunoreactive substance in renal transplant patients.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin, including those patients with end-stage renal disease. The structure and physiologic significance of this compound are unknown, and the fate of DLIS after renal transplantation has not been studied. The authors prospectively evaluated 163 patients (not receiving digoxin) before and after transplantation for the presence of DLIS. Three different assays were used: radioimmunoassay (RIA), affinity mediated immunoassay (ACA), and fluorescence polarization immunoassay (TDX I). Depending on the assay method used, 11% (RIA), 6% (ACA), and 9% (TDX) of patients had detectable DLIS pretransplant. Using all 3 assays, a total of 34 patients (21%) were found to have DLIS. The mean serum digoxin concentration was 0.41 +/- 0.13 ng/mL (range: 0.2-1.2 ng/mL) and DLIS was detectable by greater than 1 assay method in seven patients. DLIS persisted longer in patients who had delayed allograft function (13.7 +/- 7 days) than in those who did not (3 +/- 1.9 days), P less than .05. In summary, detection of DLIS in renal transplant recipients appears to be an infrequent occurrence when using a single digoxin assay method. When detected, the concentration of DLIS is often below the usual therapeutic range for digoxin and disappears once allograft function is established. The authors conclude that the presence of DLIS is unlikely to be clinically significant in the renal transplant population.

Adult↗
PubMed1991

Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy in highly sensitized renal transplant recipients.

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.

Adult↗
PubMed1990

Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone.

Prostaglandins of the E series have been shown to have immunosuppressive properties. To study the effects of the prostaglandin E1 analogue misoprostol on renal function and graft rejection after transplantation, we conducted a randomized, double-blind, placebo-controlled trial in 77 renal-allograft recipients. The subjects received misoprostol (200 micrograms four times daily by mouth; n = 38) or placebo (n = 39) for the first 12 weeks after transplantation, in addition to standard immunosuppression with cyclosporine and prednisone. They were then observed for an additional four weeks after the drug or placebo was discontinued. Treatment with misoprostol was associated with a significant improvement in renal function as judged by the mean (+/- SEM) serum creatinine concentration (128 +/- 7 vs. 158 +/- 11 mumol per liter after 12 weeks; P = 0.03) and creatinine clearance (84 +/- 6 vs. 69 +/- 5 ml per minute per 1.73 m2 of body-surface area; P = 0.05). There was a significant reduction in the incidence of acute rejection in the group treated with misoprostol as compared with the placebo group (10 of 38 vs. 20 of 39; P = 0.02), and there was less need for rehospitalization after transplantation (4 +/- 1 days with misoprostol vs. 10 +/- 2 days for placebo; P = 0.03). Although blood levels of cyclosporine did not differ significantly between the groups, they tended to be higher in the misoprostol group, as did the incidence of acute nephrotoxicity due to cyclosporine (13 of 38 vs. 8 of 39). Infectious complications tended to be fewer in the misoprostol-treated group (14 of 38 vs. 21 of 39). We conclude that misoprostol improves renal function and safely reduces the incidence of acute rejection in renal-transplant recipients treated concurrently with cyclosporine and prednisone.

Adult↗
PubMed1990

Evidence that HLA class II disparity is required for the induction of renal allograft enhancement by donor-specific blood transfusions in man.

We studied 46 living-related primary renal allograft recipients between June 1980 and Jan 1988 to determine if enhancement of allograft survival by donor specific transfusions requires a major histocompatibility complex mismatch between the blood/kidney donor and the recipient. Recipients were matched for a single HLA haplotype, but differed at various HLA loci on the unshared haplotype. DST (200 ml) was administered either 3 times at two-week intervals pretransplant (n = 17), or once 3-4 weeks pretransplant, together with oral azathioprine (1 mg/kg/day/28 days) (n = 29). Patients were followed for at least 1 year and all clinical rejection episodes were confirmed histologically. Enhanced graft survival by DST was defined as a rejection-free posttransplant course. Incompatibility for class II determinants on the unshared haplotype of donor had a beneficial effect. A significantly greater proportion of recipients had stable, rejection-free, allograft function if incompatible for the DR locus (80% vs. 44%, P = 0.012), for class II public determinants (100% vs. 58%, P = 0.013), or for at least one of the class II gene products (DR, DQ, class II public) (81% vs. 40%, P = 0.006). Graft loss occurred in 7 of 46 (15%); 6 of the 7 recipients were HLA class II-compatible with their blood/kidney donor. Mismatches for HLA class I private or public determinants and other factors known to affect graft outcome did not influence the results. We conclude that enhanced kidney allograft survival by DST may be predicated by factors within the MHC--specifically class II disparity. These observations also suggest that better HLA matching at the class II locus may account for the apparent "disappearance" of the transfusion effect in cadaver renal transplants in the cyclosporine era.

Blood Transfusion↗
PubMed1989

Reconstructive surgery for immunosuppressed organ-transplant recipients.

Prolonged vascularized organ allograft survival and an improved quality of life are now possible for many transplant recipients. These advances are due largely to greater understanding of the immune response, the development of potent immunosuppressive agents (cyclosporin A), and improved surgical techniques. Thus more of these patients may require surgical procedures related or unrelated to their original operation, and the plastic surgeon, among other specialists, should be aware of the special problems of the immunocompromised transplant recipient who needs to undergo reconstructive surgery. We report our experience with 15 kidney, heart, and liver transplant recipients who required reconstructive surgery for a variety of conditions. The combined team approach by reconstructive and transplant surgeons is described, as well as the perioperative drug protocol and the special problems that immunosuppressed transplant recipients present. We conclude that these patients can successfully undergo major reconstructive procedures as long as the plastic surgeon not only performs technically flawless surgery, but also familiarizes himself or herself with the special problems of the immunosuppressed host, including the ever-present risk of sepsis and delayed and impaired wound healing, the potential for acute Addisonian crisis, and the possibility of multiple complicating comorbid conditions.

Anti-Bacterial Agents↗
PubMed1989

Low-dose oral acyclovir for prevention of herpes simplex virus infection during OKT3 therapy.

This report evaluates the incidence of clinically significant HSV infection among 23 renal allograft recipients receiving OKT3 for treatment of steroid- or ALG-resistant acute rejection. No HSV infections occurred among the five HSV seronegative patients studied; three of 11 HSV seropositive patients (27%) treated with a ten-day course of low-dose acyclovir prophylaxis developed HSV infection. All three occurred after acyclovir was stopped. Five of six evaluable seropositive patients (83%) who did not receive acyclovir prophylaxis suffered HSV infection. We conclude that low-dose oral acyclovir may be effective in the prevention of HSV infection during OKT3 treatment of seropositive patients. Continuation of acyclovir prophylaxis for two to four weeks following the conclusion of OKT3 therapy may prevent occurrence of delayed infections.

Acyclovir↗
PubMed1988

Lipogenic activity and brown fat content of human perirenal adipose tissue.

The incorporation of 3H2O and/or 14C-glycerol into lipids and the specific activities of the enzymes acetyl CoA carboxylase and lipoprotein lipase were measured in the perirenal and subcutaneous adipose tissue of human subjects. The perirenal adipose tissue of younger subjects with higher brown adipocyte content had higher rates of lipogenesis and enzyme activities per gram tissue than the corresponding subcutaneous tissue. However, in individual specimens, the perirenal/subcutaneous ratios of all but one of the above parameters failed to show a correlation with the brown adipocyte content of the perirenal adipose tissue. One parameter, namely 3H2O incorporation into fatty acids per adipocyte, did relate to the brown adipocyte content of the perirenal adipose tissue in four normal-weight patients only.

Adipose Tissue↗
PubMed1988

The natural history of and therapy for perirenal fluid collections following renal transplantation.

Fluid collections following renal transplantation are not rare and may be associated with serious complications. We studied the incidence, clinical features, pathology and treatment outcome of perirenal fluid collections after kidney transplantation. Between January 1977 and June 1985, 386 consecutive renal transplants were performed at our university. All allografts were studied with B-mode ultrasonography together with a renal scan in the immediate post-transplant period, at 6-month intervals or when clinically indicated. Symptomatic fluid collections, those associated with rejection episodes and those containing more than 50 to 100 ml. fluid were aspirated under sonographic control via aseptic techniques. There were 190 fluid collections (49 per cent) observed during followup (2 to 11 years). Of these collections 98 (51 per cent) were estimated to be less than 50 ml. in volume, were clinically insignificant and resulted in no morbidity. A total of 92 collections was aspirated with 1 aspiration being diagnostic and therapeutic in 57 instances (serous or serosanguinous fluid). The 35 collections remaining were revealed to be lymphoceles on biochemical grounds. Of 13 lymphoceles associated with rejection episodes 8 resolved on initial aspiration. Of the recurrent lymph collections 27 were treated with repeated aspiration, tetracycline sclerotherapy or an operation (10 were treated with marsupialization into the peritoneal cavity). No large collections of urine or blood were detected and 1 infected lymphocele required external drainage. No renal allograft was lost as a result of a fluid collection and over-all graft survival was not affected by the development of perirenal fluid collections. We conclude that perirenal fluid collections are detected commonly in the post-transplant period using B-mode ultrasonography. The majority of these collections are small and will require careful observation only or they will resolve with a single aspiration. Aggressive diagnostic and therapeutic measures are used only for those collections that are symptomatic or result in allograft dysfunction. A rational approach to the diagnosis and treatment of peritransplant fluid collections is described in the form of an algorithm.

Body Fluids↗