Search PubMed⌕ Search

Biomedical subjects

W Weimar

Publications and source records attributed to W Weimar.

At least 217 records · Page 12Linked to original sources
PubMed1994

In vitro and in vivo effects of BT 563, an anti-interleukin-2 receptor monoclonal antibody.

BT 563, a murine anti-IL-2R MoAb, was found to be more potent than anti-Tac in inhibiting proliferation in the mixed lymphocyte reaction. Results obtained with 33B3.1 in these experiments were similar to those with BT 563. The anti-IL-2R MoAb 2A3 was shown to be a suitable agent for monitoring the effect of BT 563 on peripheral blood. IL-2R-positive cells were not detected in peripheral blood samples from 1 h after the first dose until 8 days after the last dose. Plasma trough levels were measured in patients receiving 5 or 10 mg daily. The administration of BT 563 to allograft recipients did not lead to clinically significant side effects.

Antibodies, Monoclonal↗
PubMed1994

Long-term survival of heart grafts in the presence of donor-specific cytotoxic T-cell precursors (CTLp) in the peripheral blood.

To monitor their immunological status we determined donor and third-party-specific cytotoxic T-cell precursor frequencies (CTLpf) in the peripheral blood of 15 heart transplant recipients. PBL samples were obtained at different time points before and after transplantation. Donor-specific CTLpf and third-party-specific CTLpf were within the same range for all samples (1-1489/10(6) cells). The donor-specific CTLpf were not different between patients who had never had an acute rejection (AR) and patients who had an acute rejection as diagnosed by endomyocardial biopsy (EMB). No difference was observed between donor-specific CTLpf of samples taken on the day of transplantation and those obtained between 3 months and 3 years after transplantation. There was also no relationship between the donor-specific CTLpf in the PBL and the culturing success of lymphocytes from EMB taken at the same time. CTLpf were in the same range both when cultures could be propagated from the graft and when no cells grew out. We conclude that long-term graft survival is possible in the presence of CTLpf in peripheral blood.

Blood Transfusion↗
PubMed1994

Cytokine gene expression profiles in human endomyocardial biopsy (EMB) derived lymphocyte cultures and in EMB tissue.

The reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to analyse cytokine gene expression in relation to acute cardiac rejection. Expression of interleukins, IL-2, IL-4, IL-6 and IL-10 mRNA was studied in sequential endomyocardial biopsies (EMB) and in graft-infiltrating lymphocyte (GIL) cultures propagated from EMB taken after heart transplantation. The cytokine gene expression of GIL propagated from EMB taken during an episode of rejection and of immunological quiescence was comparable. In contrast, posttransplant EMB showed selective IL-2 gene expression when rejection was diagnosed. IL-4 mRNA was absent in pretransplant EMB but present in posttransplant EMB taken during periods of rejection and of immunological quiescence. Both IL-6 and IL-10 transcripts were found in pre- and posttransplant EMB. These findings confirmed that IL-2 is specifically involved in cardiac rejection, while IL-4 may play a role in immune responses leading to graft rejection or graft tolerance.

Biopsy↗
PubMed1994

Discrepancy between mRNA expression and production of IL-2 and IL-4 by cultured graft infiltrating cells propagated from endomyocardial biopsies.

We studied whether acute rejection correlated with the cytokine production pattern and mRNA expression of interleukin-2 (IL-2) and interleukin-4 (IL-4) in lymphocyte cultures derived from endomyocardial biopsies (EMB) that were stimulated with B cell lines of donor origin. Unstimulated biopsy cultures neither expressed mRNA nor produced IL-2 or IL-4. All stimulated biopsy cultures contained mRNA transcripts for IL-2 and IL-4. In contrast, we found different IL-2 and IL-4 production patterns. Within the first 90 days after heart transplantation (HTx), higher levels of IL-4 were measured in cultures derived from EMB with myocytolysis than in cultures from EMB without signs of myocytolysis. More than 90 days after HTx, this phenomenon was reversed and more IL-4 was produced in cultures derived from EMB without myocytolysis. These differences were not detected for IL-2 production.

Biopsy↗
PubMed1994

Time course of the decline in renal function in cyclosporine-treated heart transplant recipients.

The renal side-effects are a major limitation of the use of cyclosporine A (CsA) following heart transplantation. In an effort to define the time course of the decline in renal function and to identify a group of patients especially prone to the nephrotoxic effects of CsA, we studied 187 orthotopic heart transplant recipients who had a follow-up of at least 1 month. All patients received oral CsA in a starting dose of 8 mg/kg and low-dose steroids. Renal function decreased steadily after transplantation. Serum creatinine was > 150 mumol/l in 52% of the patients after 2 years. After 4 years serum creatinine was > 250 mumol/l in 13% of the patients. No relation could be found between the decline in renal function (as defined by the slope of serum creatinine-1 versus time) and age, sex, creatinine levels before transplantation, blood pressure, CsA blood levels, the number of rejections or the use of calcium channel blocking drugs. We conclude that, despite reduction of CsA dosage, progressive renal insufficiency can be observed in an increasing percentage of heart transplant recipients. We were not able to identify patients with a poor renal prognosis in an early phase after transplantation.

Adult↗
PubMed1994

Effect of isradipine on cyclosporin A-related hypertension.

There is evidence that calcium antagonists may have a beneficial effect on cyclosporin A (CyA)-induced hypertension after organ transplantation. In a double-blind controlled trial, 50 consecutive non-diabetic first kidney-transplant recipients were randomized to receive either isradipine, a dihydropyridine calcium antagonist, or placebo. There were no significant differences in age, weight, gender, warm and cold ischaemic periods, and original renal disease between treatment groups. Treatment was started intravenously 2 h before the transplantation procedure and was subsequently continued orally for 3 months. The immunosuppressive treatment included oral CyA from day 5 after a short course of anti-T-lymphocyte immunoglobulins. Hypertension was treated with oral labetolol in combination with guanfacine if necessary. Antihypertensive medication was prescribed significantly more often (16 vs 7 patients; p < 0.05) in the placebo group. Standing systolic blood pressure was significantly lower in the isradipine group. The standing diastolic and both systolic and diastolic sitting blood pressures were similar in both groups. After 3 months, patients' mean serum creatinine was significantly lower with isradipine than with placebo (142.0 +/- 11.9 vs 164.0 +/- 10.8 mumol/l; p < 0.05). With isradipine, a significantly higher dose of CyA was needed to achieve adequate plasma levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg/day; p < 0.01). It can be concluded that isradipine is an effective antihypertensive agent after kidney transplantation and may have an influence on CyA metabolism. Furthermore, isradipine appears to ameliorate CyA-induced nephropathy.

Blood Pressure↗
PubMed1993

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation.

We studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37 male/21 female) consecutive renal allograft recipients were entered in this trial. Treatment results were compared with 56 patients treated with intravenous cyclosporin (CyA). In all patients concomitant medication consisted of steroids and azathioprine, followed by oral CyA. Following rabbit ATG, T cells (WT31) quickly disappeared from the peripheral blood and a return to greater than 100/mm3 was observed at a median of 7 (range 3-21) days. Graft survival was the same in both groups, as was the incidence of primary nonfunction. The rate of acute rejection was significantly lower in the rabbit ATG-treated patients (12% vs 50%). We conclude that a single shot of rabbit ATG is an attractive, easy, and cost-effective induction scheme with a low incidence of delayed graft function and acute rejection episodes. A relatively high incidence of vascular thrombosis of the graft, however, warrants further study before this treatment regimen can be generally applied.

Adolescent↗
PubMed1993

Donor heart endothelial cells as targets for graft infiltrating lymphocytes after clinical cardiac transplantation.

The in vitro cytotoxic reactivity of allograft infiltrating cells cultured from endomyocardial biopsies was tested against endothelial cells (EC) isolated from the own donor heart. EC derived from pieces of atrium were found to be proper targets for graft infiltrating cytotoxic T cells from four patients. The specificity of this cytotoxicity was further analysed by cold target inhibition studies and blocking with anti-CD3, anti-CD4 or anti-CD8 monoclonal antibodies. The experiments revealed that, besides a clearly HLA directed recognition, a more heterogeneous, multispecific response can be found, which might be partially explained by the activity of EC specific T cell clones. We conclude that this system provides a valuable approach to investigate the reactivity of graft infiltrating cells against EC in relation to the clinical course of the transplantation.

Antibodies, Monoclonal↗
PubMed1993

Altered specificity of alloreactive cardiac graft-infiltrating cells by prophylactic treatment with OKT3 or horse antilymphocyte globulin.

Graft-infiltrating lymphocytes from patients who were prophylactically treated with OKT3 or horse antilymphocyte globulin (H-ALG) were found to have different specificity patterns from those in the control group that received cyclosporine from the day of transplantation. This prophylactic treatment led to a significant decrease of the HLA-DR-directed cytotoxicity, while the cytolytic response against HLA-class I mismatches was hardly affected. In H-ALG patients without rejection, the percentages of class I-reactive cultures were found to be lower than in the other treatment groups, which was mainly due to a lower percentage of HLA-B--reactive cultures. In CsA and OKT3 patients, cytotoxic T cells were rather directed to HLA-B mismatches than to HLA-A antigens, while in H-ALG patients no difference in HLA-A and B-directed cytotoxicity was found. Our data suggest that OKT3 and H-ALG influence the specificity of the T cell allorepertoire, resulting in a decreased frequency of class II-specific cytotoxic T cells after transplantation. H-ALG also has a downregulating influence on the CTL response against HLA class I (HLA-B) antigens. In some patients a fast regeneration of these cells occurs, which results in a higher rejection incidence during the first posttransplant year.

Antilymphocyte Serum↗
PubMed1993

The detection of cytotoxic T cells with high-affinity receptors for donor antigens in the transplanted heart as a prognostic factor for graft rejection.

Alloreactive T lymphocytes are the initiators and effectors of acute rejection of organ transplants, and T cells with high-affinity receptors for antigen might be especially implicated in this process. It has been shown that the cytotoxic capacity of CTL with low affinity for alloantigens can be inhibited with CD8 mAb, while high-affinity CTL are not affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejection, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute rejection and 10 who had had one or more rejection episodes. IN the rejectors, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were found compared with the nonrejectors (medians of 10,586 vs 1,169 reactive cells per 10(6) tested cells, P = 0.002). After CD8 inhibition, the difference between rejectors and nonrejectors was even more pronounced (P < 0.001). In patients with rejection, the number of CD8-resistant, high-affinity CTL was higher than 1000 per million cells in all cases, while in patients who had never experienced rejection this number was less than 1000. As these CTL characteristics are already present before the first histological signs of rejection have developed, this might be used as a prognostic factors.

Antibodies, Monoclonal↗
PubMed1993

Cortical blindness due to cyclosporin.

We here report the occurrence of cortical blindness in a kidney transplant recipient treated with cyclosporin. The cortical blindness was the result of cyclosporin toxicity and resolved spontaneously after cyclosporin dose reduction.

Blindness↗