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V C Marshall

Publications and source records attributed to V C Marshall.

At least 19 recordsLinked to original sources

The effect of ureteric stenting on the function and morphology of long-term rat renal allografts.

In the development of a reliable model for chronic rejection in rat renal allografts, the effect of modifying the ureteric anastomosis was tested. Rats, tolerized by pretreatment with two donor blood transfusions under Cyclosporin A, received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.

Animals↗

A reproducible model of chronic rejection in rat renal allografts.

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 66% after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.

Animals↗

Development of chronic injury and nature of interstitial infiltrate in a model of chronic renal allograft rejection.

A model of chronic renal rejection in the Dark-Agouti to Albino-Surgery rat combination is described. In a number of cases, the original allograft was replaced by a second Dark-Agouti allograft. Seventy-five percent of rats experienced early episodes of rejection that subsided spontaneously. Second allografts had better initial renal function. Variable degrees of tubular atrophy, interstitial fibrosis, vascular damage, glomerulosclerosis, deposition of humoral mediators, and mononuclear leukocyte infiltrate were observed in all long-term allografts. Chronic damage increased with time, and was less severe in second allografts. At 5 days, total interstitial infiltrate was similar to that seen in unmodified rejection, but there was a significant increase in CD4+ cells and a decrease in ED2 and IL-2R expression. Subsequently, the total interstitial infiltrate decreased with time, although it remained significantly higher than in isografts and residual kidneys from uninephrectomized rats. No significant decrease over time was seen in numbers of CD4+ and CD45RC+ cells. The latter had a marked focal distribution after 100 days. Total leukocyte infiltrate was similar in original and second allografts, but there were changes in the proportions of leukocyte subpopulations, including significantly lower numbers of CD45RC+ cells in the latter. The persistence of CD45RC+ cells throughout the course of chronic rejection and their lower numbers in the second allografts favors a role for these cells in the development of chronic injury. The model of chronic renal allograft rejection characterized in this study will be valuable in further studies of the mechanisms of injury in this pathology.

Animals↗

The evolution of the interstitial infiltrate in rejecting rat renal allografts: with particular reference to the production of gamma-interferon.

This study aimed to examine the evolution of the leucocytic infiltrate in rat renal allografts in the first 5 days of rejection. Immunohistology was used to assess the absolute numbers of infiltrating leucocytes in the rejecting allografts. The total infiltrate approximately doubled daily from day 1 through to day 4 (370 +/- 15 total leucocytes/mm2 of tissue on day 1 vs 5055 +/- 135 on day 4, p less than 0.05 for all days) and increased only a minor degree on day 5 (5485 +/- 535 leucocytes/mm2, p = n.s.). CD4 positive cells predominated until day 3, after which time CD8 positive cells greatly outnumbered CD4 positive cells (CD4:CD8 ratio day 3 1.83 vs day 5 0.53, p less than 0.05). Gamma-interferon was positive in T cells on day 2 (73% of all T cells) and was slightly positive on day 3 (5% of all T cells) but was negative on days 4 and 5. Activation markers such as IL-2Rs increased markedly from day 3. These findings favour a pivotal role for CD4 positive cells in the early phase of rejection and suggest that the early release of lymphokines by these cells is associated with the recruitment of CD8 positive cells to the allograft and the activation of those leucocytes present.

Animals↗

Liver preservation with UW solution. I. Evidence that hydroxyethyl starch is not essential.

Preservation of rat livers by simple ice-storage has been demonstrated after 24 hr using the University of Wisconsin (UW) solution. Equally good preservation could be obtained by substituting hydroxyethyl starch (HES) from another source or by omission of HES from the UW formulation. Survival, early and late function, and morphology at the end of a 3-month follow-up period were essentially similar for all three test groups. It is concluded that HES is not required for optimum preservation of the rat liver in this treatment model.

Adenosine↗