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R D Guttmann

Publications and source records attributed to R D Guttmann.

At least 145 records · Page 8Linked to original sources
PubMed1982

Evidence for complement-induced endothelial injury in vivo: a comparative ultrastructural tracer study in a controlled model of hyperacute rat cardiac allograft rejection.

In order to delineate the potential role of platelet-derived factors and of the direct lytic action of complement in the pathogenesis of endothelial injury in hyperacute allograft rejection, a highly reproducible and rigidly controlled inbred rat cardiac model was studied, utilizing colloidal carbon as a vascular tracer for comparative ultrastructural analysis of the microcirculation. Unmodified allografts were characterized by widespread intramural carbon labeling of the microvasculature, which corresponded to sites of platelet sequestration and extensive endothelial cell disintegration. Under conditions of recipient platelet depletion without concomitant complement depression, carbon-labeled segments of the microcirculation showed widespread endothelial cell disintegration, the ultrastructural features of which were similar to those observed in the unmodified allograft group. The microvasculature of syngeneic heart grafts transplanted to platelet-depleted recipients as well as all platelet-depleted recipients' own hearts showed no similar ultrastructural changes. It is thus concluded that the loss of cellular integrity of the microcirculatory endothelium in hyperacute rat cardiac allograft rejection is not a platelet-dependent phenomenon. The current ultrastructural data combined with previous morphologic studies provide strong evidence that the severe form of endothelial injury observed in this model is mediated by the direct action of activated complement components.

Animals↗
PubMed1981

Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.

Animals↗
PubMed1981

Development of anergy to delayed-type hypersensitivity antigens following renal allotransplantation.

A study is reported of patients receiving 180 renal allotransplants and at risk for 1 or more years who had pretransplant and posttransplant skin tests using delayed type hypersensitivity (DTH) recall antigens. Pretransplant skin testing revealed an incidence of 14% anergic patients prior to a first transplant, and 35% were anergic prior to a second allograft. There was a statistically significant correlation between pretransplant anergy and age, as well as a significant correlation between pretransplant anergy and time of dialysis-dependent uremia. The conversion to the anegic state posttransplant in those patients with surviving allografts increased annually for the first 5 years as a linear function, with 69% of the population at risk with their first transplant exhibiting anergy by 5 years. In those patients receiving second renal transplants, all were anergic by 4 years posttransplant. In vitro tests of lymphocyte function using mitogen stimulation did not reveal significant differences between anergic and responsive patients. In this series of 180 allografts there were 14 late deaths. Eleven of these were in anergic patients and in 10 instances were related to sepsis or malignancy. Three patients who were skin-test responsive at the time of death died from cardiovascular causes. It is concluded that there is an increasing risk of the development of anergy to DTH antigens posttransplant and that the type of late mortality may be marked by this hyporeactive state.

Adult↗
PubMed1981

Studies of the effects of alloimmunization on the local graft-versus-host reaction in the rat.

A model of rat graft-versus-host reactivity (GVHR) has been studied using lymphoid cells obtained following i.v. immunization of the parental strain donor with allo- or xenoantigens. Twenty-four hours after immunization with 10(7) F1 hybrid bone marrow cells, spleen cell reactivity inducing GVHR was increased, contrasting with decrease peripheral blood lymphocyte reactivity. This is probably attributable to an alloantigen-induced recruitment of GVH-reactive cells in the spleen. From the 3rd day up to 6 weeks after immunization, spleen cell and peripheral blood lymphocyte GVHR remained low. The suppression was nonspecific and was observed over a wide dose range of allogenic and semiallogeneic lymphoid cells of different origins. Allogeneic red blood cells and platelets were also effective in inducing suppression, but xenogenic lymphocytes and red blood cells were inefficient. The ability to induce suppression remained after heat killing the immunizing cells for 2 hr at 45 C, but disappeared if they were heated for 30 min at 56 C. In one of the two strain combinations studied, mixing experiments suggest that the suppression observed 1 week after immunization with 10(7) F1 hybrid bone marrow cells, a protocol used to achieve active enhancement of organ allograft, might be attributable in part to a nylon-wool-nonadherent suppressor cell.

Animals↗
PubMed1981

Altered immunoregulatory function in long-term renal allograft recipients.

In order to determine immunoregulatory lymphocyte subsets in patients with long surviving renal allografts, a study utilising functionally characterised monoclonal antibodies with analysis by flow cytometry using a Fluorescence Activated Cell Sorter was carried out. Cells from 35 patients with allograft survival from one to 15 years were analysed with monoclonal antibodies for the following markers: inducer-helper, cytotoxic-suppressor, monocytes, Ia, IgG and IgM. Control groups consisted of long-term dialysis patients and a group of normal individuals. The results show a strikingly significant difference between the long-term allograft recipients and the control population in terms of the inversion of the normal inducer-helper to cytotoxic-suppressor ratio. Additionally, there were significant differences in the number of Ia+ cells in long-term transplant patients and dialysis patients compared with normals. No impressive differences were found in the numbers of Ig bearing cells. Thus the long-term allograft state is a clear example of an overabundance of cellular suppression and may explain many of the general phenomena seen in surviving recipients.

Cytotoxicity, Immunologic↗
PubMed1980

Insulin dependent diabetes: a comparison of families with single and multiple affected siblings.

Families (n = 14) with more than 1 sibling with insulin dependent diabetes were matched with families of similar size and age distribution containing only 1 affected child. The distribution of HLA haplotypes, age of onset of disease, and seasonal onset of disease were compared in the two groups. The data are not consistent with the hypothesis of a single autosomal recessive gene linked to the HLA region. The data do not permit a choice between other current hypotheses although they are compatible with the theory of 2 genes linked to the HLA region, acting additively, and requiring interaction either with environmental factors or other disease susceptibility genes. Diabetic children in the multiplex and simplex families did not differ in the month of onset of symptoms nor in the age at diagnosis although three multiplex pedigrees in which diabetes developed in all affected children before the age of 6 years were identified.

Adolescent↗
PubMed1980

Differential susceptibility of cardiac cell populations to in vitro immune injury.

In vitro, the culture of enzymatically dissociated fetal heart cells results in the formation of contractile cellular islets surrounded by monolayers of static cells. The islets contract in a spontaneous and synchronous fashion. Using inbred strains of rats sensitized by an allogeneic heart transplant or by three consecutive skin grafts, immune sera were obtained that were assayed at various dilutions against the cell cultures with or without complement. Strain-specific and selective lysis exclusively directed against the static cells was observed. This suggests that noncontractile cells were the specific targets for alloantibody in this fetal heart cell culture system.

Animals↗
PubMed1980

Cardiac allograft rejection and enhancement in natural recombinant rat strains.

Cardiac allografts were carried out using rat strain combinations with recombinant haplotypes. Rejection times were determined in unsensitized recipients, recipients that had been immunized to produce hyperacute or accelerated rejection, and recipients that had been i.v. immunized with 10(7) bone marrow cells to produce active enhancement. The graft survival results obtained suggest that there is a major influence of the A region or classical type I transplantation antigens in first set and hyperacute rejection whereas immunization to both A or B region (Ia) antigens may produce markedly prolonged survival. These data suggest major differential influences of major histocompatibility complex (MHC) subregions depending on the specific donor-recipient incompatibility as well as suggesting major influences in these three allograft models depending on the background of the strain used.

Animals↗