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R D Guttmann

Publications and source records attributed to R D Guttmann.

At least 181 records · Page 10Linked to original sources
PubMed1977

In vitro correlates of rejection. I. Suppressive effect and specificity in mixed lymphocyte interaction of alloantiserum producing hyperacute rejection.

A hyperimmune antiserum from WfBN F1 hybrid rats primed to hyperacutely reject LBN F1 cardiac allografts has been studied. A large volume of antiserum will cause allograft rejection in less than 1 day. In the in vitro MLI, concentrations of this antiserum as low as 0.05% are markedly suppressive. This suppression is dose-dependent and immunizing-strain-specific at concentrations less than 1%. The suppressive activity is in the globulin fraction. After in vivo absorption, donor-strain specificity is clearly shown, with some cross-reactivity with third-party ACI strain. Moderate suppression of the rat MLI was seen with some normal rat sera, and augmentation of the MLI was seen in some experiments when very dilute concentrations of hyperimmune serum were used. Since suppression or augmentation of the MLI can occur as a function of antiserum dose and presumably antibody concentration, single measurements of MLI blocking factors may be misleading, and MLI suppression is not necessarily a correlate of allograft enhancement.

Animals↗
PubMed1976

A genetic survey of rat cardiac allograft rejection in presensitized recipients.

A genetic study of cardiac allograft rejection in 24 rat strain combinations sensitized by skin graft immunization has revealed that all grafts are rejected in either accelerated or hyperacute fashion. In the four strain combinations tested, the BN strain responded by rejection in hyperacute manner and the ACI strain was highly immunogenic in four strain combinations. No evidence for genic interaction was revealed by presensitization when the parental L and Bf or LBf F1 strains were studied with WfBN F1 recipients. The Lewis strain, used in many enhancement studies with BN or LBN F1 did not react with hyperacute rejection when immunized with BN. F1 hybrid to F1 hybrid haplotype-matched combinations showed accelerated rejection only. In a segregating backcross population of (L X LACI)F1, hyperactue rejection was associated with disparity at the Ag B (H-1) locus. It is concluded that the rat is a suitable species for studies of hyperacute rejection if the proper strain combination is chosen; strain-specific immune responsiveness, as well as disparity at the major histocompatibility complex and antigen dose, may be a factor in producing the phenomenon.

Animals↗
PubMed1976

In vitro monitoring of cadaver kidney donor pretreatment by lymphocyte culture.

Fourteen cadaver kidney donors were pretreated with a rapid infusion of 5 g of cyclophosphamide and 5 g of methylprednisolone in an attempt to reduce graft immunogenicity by altering immunogenic "passenger" leucocytes. The effects of this drug infusion on peripheral lymphocytes were monitored by measuring the ability of donor lymphocytes to respond and to stimulate recipient cells in mixed lymphocyte culture and by measuring their ability to respond to phytohaemagglutinin stimulation before and after infusion of the drugs. Pretreatment severely decreased the ability of donor cells to function in these tests, but the maximum effect was not seen until several hours after completion of the infusion. The results of this study suggest that donor nephrectomy should be delayed for at least 4 hr after pretreatment to obtain maximum lymphocyte effect using this regimen. This type of in vitro testing may provide means of monitoring donor pretreatment and comparing different pretreatment protocols in human cadaveric allotransplantation.

Antibody Formation↗
PubMed1976

Nonessential role of neutrophils as mediators of hyperacute cardiac allograft rejection in the rat.

The presence of neutrophils within the graft has been widely emphasized as a characteristic feature of hyperacute rejection, and analogies have been drawn to the Arthus reaction, in which neutrophils are essential mediators of tissue damage. To evaluate the role of neutrophils as mediators of graft destruction in hyperacute rejection, we studied a series of 16 heterotopic ACT strain rat cardiac allografts in skin-presenitized Lewis strain recipients, all of which recieved prior treatment with cyclophosphamide and methotrexate or heterologous rabbit antirat polymorphonuclear globulin. Fourteen recipients showed significant depression in levels of circulating neutrophils prior to transplant, and neutrophils were not detected in 13 allogrates at the time of functional rejection. There was no abrogation of hyperacute rejection in this series and the characteristic pattern of vacular and myocardial damage was not altered by the absence of neutrophils from the graft. Although the possibility that neutrophil-derived agents may contribute to late graft destruction cannot be excluded, this study has shown that neutrophils are neither essential nor specific participants in hyperacute allograft rejection in this model.

Animals↗
PubMed1976

Manipulation of allograft immunogenicity by pretreatment of cadaver donors.

The experimental basis forming the rationale for the reduction of allograft immunogenicity prior to transplantation is described. This is based on the hypothesis that ""passenger leucocytes'' are a major immunogenic stimulus in rejection. Donor pretreatment with high doses of methylprednisolone and cyclophosphamide can be used clinically for cadaver donor pretreatment and when combined with an adequate post-transplant chemical immunosuppressive regimen results in an important in improvement in overall results as seen in a series followed for 5 1/2 years.

Animals↗
PubMed1975

Extensive intraglomerular fibrin deposition after renal transplantation: recovery without anticoagulation.

Acute renal failure developed in a 55-year-old man 6 days after he had received a cadaver renal allograft. This was associated with thrombocytopenia. Extensive intraglomerular fibrin deposition was seen in a renal biopsy specimen. He was treated with corticosteroids, azathioprine, cyclophosphamide and hemodialysis with regional heparinization but not with systemic anticoagulation. This was followed by complete recovery of both renal function and histologic damage despite the fact that he did not receive anticoagulant therapy. This suggests that treatment with anticoagulants may not be necessary for all patients with intraglomerular deposits of fibrin.

Acute Kidney Injury↗
PubMed1975

Antilymphocyte globulin in renal transplantation: Nephrotic syndrome and infection as possible complications.

During a two-year period, nine patients received equine antilymphocyte globulin (ALG) as part of their immunosuppressive therapy following cadaver renal transplantation. Of these, three patients (33%) developed nephrotic syndrome. A fourth patient had proteinuria greater than 3 gm/24 hr not attributable to recurrent disease or rejection. Of 32 other patients with cadaver renal allografts done during the same time, none had nephrotic syndrome and two (6%) had proteinuria greater than 3 gm/24 hr, both with biopsy evidence of rejection. This suggests an association between ALG therapy and risk for developing nephrotic syndrome, but the mechanism is not clear and deserves further investigation. During the first three months following transplantation, the nine patients treated with ALG had 20 infections, which seems to be more per patient than in our other transplant recipients.

Adolescent↗
PubMed1975

A controlled sequential morphologic study of hyperacute cardiac allograft rejection in the rat.

A series of heterotopic cardiac allografts from ACI strain rat donors to ACI skin-presensitized Lewis strain recipients was examined by light and electron microscopy at intervals from 1 minute to 24 hours for a sequential morphologic study of hyperacute rejection. Syngeneic Lewis hearts grafts in ACI skin-presensitized Lewis recipients provided controls. Extensive platelet aggregation throughout the vasculature of the allografts in the presence of a largely intact endothelium was the initial morphologic event, which was present by 1 minute posttransplant and absent in all syngeneic controls. This was followed by widespread endothelial damage. Endothelial damage preceded neutrophil margination and emigration in the graft. Neutrophil degranulation or evidence of phagocytosis was not observed within the 1st hour. At 6 and 24 hours, degranulated forms were common and apparent extrusion of granule contents with progressive ischemic injury. Segmental occlusion of the vasculature by platelet plugs and progressive disruption and loss of capillaries combined with an increase in permeability may result in myocardial ischemia. Neutrophil-derived agents do not appear to be of major significance in hyperacute rejection during the early posttransplant phase, but may play a role in mediating myocardial injury if the allograft survives for alonger period. However, on morphologic grounds, it is suggested that microcirculatory hypoperfusion with resultant ischemia is a major determinant of myocardial damage and graft function. No significant change was noted over the observation period in peripheral neutrophil or platelet counts when compared to syngeneic controls, and a slight reudction in specific cytotoxic antibody titer in the allografts was immediate but very transient.

Animals↗