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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 271 records · Page 15Linked to original sources
PubMed1985

Suppression of antibody response and prolongation of skin graft survival by multiple blood transfusions in the rat.

The effect of blood transfusions (BT) on antibody response and skin graft survival was studied in the strongly MHC-incompatible BN and LEW combination. One-to-three BT induced high titer antibodies. Additional BT, however, led to a decrease of antibody titers. After 15 BT the recipients either had no detectable antibodies, or they had very low antibody titers. This suppression of response was shown to be distinct from a simple loss of antibody activity caused by lack of further antigenic challenge. In multiple transfused rats, humoral nonreactivity persisted in spite of rechallenge with antigen; in animals that lost their antibodies as a result of lack of further stimulation, an additional BT boosted strong antibody production. In LEW recipients of multiple BN transfusions, not only the specific anti-BN response but also reactivity to third-party BUF blood was suppressed. However, whereas the donor-specific response (anti-BN) was largely inhibited after a ten-week interval, the response to third-party BUF blood recovered. The state of humoral nonreactivity could be transferred by spleen cells to nontransfused syngeneic animals. In LEW rats that received three injections of 5 X 10(7) "suppressor" spleen cells, the antibody response to BN blood was strongly impaired as compared with animals that received normal spleen cells. BN or (BN X LEW)F1 skin grafts survived significantly better in multiple transfused LEW rats than in nontransfused controls. This was even more pronounced when ALS was given additionally. Third-party grafts (BUF) survived only slightly better than controls. It is concluded that multiple BT (1) result in humoral anti-donor nonreactivity secondary to an initial antibody response, (2) induce strong specific and weak nonspecific suppressor cell activity, and (3) increase skin graft survival.

Animals↗
PubMed1985

Correlation of HLA matching with kidney graft survival in patients with or without cyclosporine treatment.

In a series of more than 8000 first cadaver transplants performed during a two-year period, 2198 recipients treated with cyclosporine had a higher graft survival rate (76 +/- 1% at 1 year) than 6392 recipients without cyclosporine (64 +/- 1%, P less than 0.0001). Matching for HLA-B plus HLA-DR resulted in a significant correlation with graft outcome, in patients with or without cyclosporine treatment (P less than 0.0001). Regardless of whether cyclosporine was used or not, grafts with 0 HLA-B,-DR incompatibilities had approximately 20% higher success rates at one year than grafts with 4 mismatches. A high (86 +/- 3%) graft survival rate was obtained in 161 cyclosporine-treated recipients with 0 HLA-B,-DR mismatches. Matching for the HLA-B and HLA-DR loci is shown to have an additive effect in cadaver kidney transplantation.

Cyclosporins↗
PubMed1985

Suppression of antibody response to transfusions in rats by preconditioning with antibody-coated cells.

In a Lewis-BN rat model, the antibody response to transfused blood cells from strongly histoincompatible donors was suppressed by preincubation of blood with specific antidonor antiserum or broadly reactive heterologous antilymphocyte serum (ALS). Suppression was achieved even when excess antiserum was removed by washing prior to injection. The suppressive effect was dose-dependent. Broadly reactive ALS was even more effective than specific antidonor antiserum in inhibiting the primary antibody response. Lewis animals pretreated three times with ALS-coated BN blood showed no secondary antibody response against subsequent BN-blood booster injections. Our experiments may be relevant for the prevention of undesired sensitization to donor-specific transfusions prior to related donor kidney transplantation.

Animals↗
PubMed1985

Transfusion-induced enhancement of prostaglandin and thromboxane release in prospective kidney graft recipients.

Pre-transplant blood transfusions (BT) improve the survival of kidney grafts. Apart from specific immunoregulation by T suppressor cells or anti-idiotypic antibodies, the role of non-specific immunoregulatory factors, such as prostaglandins is being discussed as a possible mechanism for this effect. We studied the in vitro prostanoid release from peripheral mononuclear cells following three deliberate blood transfusions. Twenty-five previously non-transfused dialysis patients were studied. Spontaneous and LPS-induced prostaglandin E (PGE) and thromboxane B2 (TXB2) were determined in cell-free culture supernatants by fluid phase RIA. Transfused patients exhibited a more rapid onset and steeper increase of prostanoid production. After 24 hours incubation, the spontaneous and LPS-induced PGE release of pre- and post-BT cells was significantly different (pre-BT: 2.1 and 5.1 ng/ml; post-3-BT: 5.0 and 7.9 ng/ml; p less than 0.01). Pre-BT cells released considerably lower amounts of TXB2 than post-BT cells (spontaneous release: 39 vs 88 ng/ml; LPS-induced release: 62 ng/ml vs 129 ng/ml; p less than 0.05). After correction for monocytes as defined by monoclonal antibodies, post-BT cells again showed increased prostanoid release as compared to pre-BT cells. Therefore, the enhanced PGE and TXB2 release of post-BT cells is not caused by an increase merely in the number of monocytes. Rather, BT appear to induce an enhanced release of prostanoids by activation of monocytes. We also found a correlation between the number of BT and the amount of prostanoid release.

Adolescent↗
PubMed1985

HLA matching and cadaver kidney transplantation--status 1984.

The effect of HLA matching on cadaver kidney graft survival was analysed in over 9000 transplants. Matching for HLA-A and -B accounted for an improvement of 8% in the one-year survival rate, matching for HLA-DR for 10%, and matching for HLA-B + DR for 19%. The matching effect of the HLA-B and HLA-DR loci was additive. Patients without pre-transplant transfusions had lower graft survival rates than transfused patients, even if their grafts were HLA matched. The highest success rate was obtained in transfused recipients who received HLA matched kidneys.

Cadaver↗
PubMed1985

Analysis of HLA matching in relation to kidney preservation time.

The effect of HLA matching on cadaver kidney graft survival was analyzed in relation to the length of cold ischemic kidney preservation prior to implantation. The best correlation was seen when ischemia was greater than 36 hr, however, even with less than 24 hr ischemia there was a good correlation of matching with graft outcome. Importantly, HLA matched kidneys with greater than 36 hr ischemia performed very well, better than poorly matched kidneys with short ischemia.

Actuarial Analysis↗
PubMed1984

A rapid screening technique for lymphocytotoxic antibodies using tray-frozen lymphocytes.

A method whereby sera can be screened for the presence of lymphocytotoxic antibodies within 4 hr using lymphocytes frozen in microtest trays is described. The reactions of the sera of 48 hemodialysis patients against freshly prepared lymphocytes were compared with those against tube-frozen (384 reaction pairs) and tray-frozen (864 reaction pairs) cells. There was a better than 90% concordance, and only 3% of the reactions differed from negative to strongly positive or vice versa. Preliminary results indicate that the method is also suitable for B-cell (HLA-DR) antibody testing. Routine screening against 50- or 100-cell panels can be accomplished more rapidly and more efficiently using tray-frozen lymphocytes. The data matrix for analysis of a serum's HLA specificity is greatly reduced in comparison to the conventional screening technique, rendering the method particularly suitable for microcomputer processing.

Antilymphocyte Serum↗
PubMed1983

Immunological factors influencing renal graft survival.

The results of clinical renal transplantation are determined mainly by immunological factors, the most important of which are compatibility for the HLA chromosomes and pretransplant blood transfusions. Other factors include HLA matching in cadaver transplantation, compatibility for the Lewis blood group system, and sensitization to lymphocyte panels or to endothelial-monocyte antigens. Performance of the previous graft is the most reliable predictor of success in recipients of retransplants. Because several immunological factors may interact, multiple variables must be considered simultaneously.

Blood Transfusion↗
PubMed1983

HLA phenotypes and idiopathic nephrotic syndrome in children.

Ninety-four children with idiopathic nephrotic syndrome (17 steroid-resistant with a histological diagnosis of a focal segmental glomerulosclerosis) were typed for HLA-A, B and DR antigens. The patients showed a significant increase of DR7 (58% vs 18%, p less than 0.0001) and of B8-DR3 (27% vs 5%, p less than 0.05). Combination of both markers (DR7 and B8-DR3) was observed in 14 per cent of patients but in none of the controls (relative risk 15.2). Patients with B8-DR3 and DR7 had a more severe course of INS.

Child↗
PubMed1982

Advantage of cold storage over machine perfusion for preservation of cadaver kidneys.

Evidence is provided that, with cold ischemia up to 48 hr and warm ischemia up to 60 min, simple storage preservation results in equally good or better transplant success rates than pulsatile machine perfusion. In the critical 24- to 43-hr preservation period, 1-year survival rates were 53 +/- 3% for 282 kidneys preserved in Collins solution, as compared with 40 +/- 2% for 565 kidneys on the Belzer machine (P less than 0.0001) and 48 +/- 1% for 1441 kidneys perfused on the Waters machine (P = not significant). Warm ischemia of 40 to 60 min also yielded better results with simple cold storage than with machine preservation (P less than 0.05). Although it has been maintained that one of the functions of preservation machines is to select out kidneys of poor quality, we found that this preselection actually has resulted in lower transplant survival rates. Because storage in Collins solution is simpler, safer, and much less expensive, we conclude that there is no longer any reason to preserve kidneys by pulsatile perfusion on machines.

Cold Temperature↗
PubMed1982

International study of histocompatibility in renal transplantation.

With international collaboration, data on more than 2000 cadaver donor transplants were collected and analyzed. In first transplants, the number of pretransplant transfusions given to the recipients correlated significantly with graft survival (P less than 0.0001). No correlation of graft outcome was found with matching for HLA-A,B. HLA-DR matching was significantly correlated with outcome in the North American transplants, but not in the European subset of transplants. In second transplants, HLA-DR matching and the duration of the first transplants correlated significantly with graft survival, whereas there was no correlation with HLA-A,B matching or transfusions.

Blood Transfusion↗
PubMed1982

[Current immunologic aspects of kidney transplantation].

The results of clinical kidney transplantation are mainly dependent on immunologic factors many of which are unknown or of unspecified importance. Blood transfusions have a favorable effect on graft prognosis, although our knowledge about optimal transfusion protocols and transfusion-induced mechanisms is still incomplete. The value of HLA-typing is controversial: whereas compatibility of the "classical" HLA-A,B,C antigens improves graft survival only moderately, HLA-DR typing, routinely performed for the last 3 years only, might be of greater importance. In addition, non-HLA systems, such as endothelial/monocytic antigens or the Lewis blood group system, appear to play a role in graft rejection. The individual immune reactivity a recipient to a large extent determines the fate of a graft. The multifactorial dependence of graft prognosis is discussed in this report.

Blood Group Incompatibility↗
PubMed1981

Induction of high kidney graft survival rate by multiple transfusion.

In 33 centres that adopted a policy of liberal preoperative blood transfusion 174 recipients of cadaver donor transplants were followed up. Those who received no pretransplant transfusions had a 23% 1-year graft survival rate whereas those who had greater than 10 transfusions had an 87% survival rate (p less than 0.000001). 3% of those transfused acquired highly reactive cytotoxic antibodies and greater than 70% had no antibodies, so transfusions do not exert their beneficial effect by excluding strong immune responders. Since transplant survival rates improved with the number of transfusions, they probably produce their beneficial effect by inducing a state of unresponsiveness. Multiple transfusion seems a simple and effective way of improving kidney transplant survival rates. Moreover, the immunosuppressive effect is specific in that it does not alter the immune response to infectious agents.

Blood Transfusion↗