Biomedical subjects
Publications and source records attributed to M Bustos.
Six years ago, Jeffrey Platt and colleagues reviewed the biological hurdles to transplanting organs between species. The ensuing years have allowed the concepts advanced at that time to be tested leading to significant progress in understanding the immunology of xenotransplantation and in developing strategies for potential clinical application. Here, William Parker and colleagues review that progress.
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Immunohistochemical techniques were used to study the presence of ciclosporin A (CsA) and leukocyte subsets in 36 posttransplant renal biopsy specimens histologically diagnosed as acute graft rejection. Glomeruli from patients with CsA deposits contained more leukocytes (p < 0.05) than glomeruli from tissues without deposits. In contrast, the interstitium from patients without deposits contained significantly more B lymphocytes than interstitia from kidneys with CsA deposits. In both glomeruli and interstitia, the CD4/CD8 ratios were higher in tissues without deposits, although the difference was not significant. The plasma levels of creatinine increased with the intensity of renal CsA deposits, and significantly more patients on hemodialysis had deposits as compared with patients not on hemodialysis. Our findings suggest two types of acute nonvascular rejection: (1) predominantly interstitial, with a good prognosis, characterized by low numbers of intrarenal CsA deposits and a predominance of B lymphocytes and (2) predominantly glomerular, with a poor prognosis, characterized by high levels of intrarenal CsA and a predominance of CD8-positive cells and macrophages.
The influence of immunosuppressant therapy and of the presence of CMV genome on the distribution of lymphoid subpopulations of the inflammatory infiltrate in renal graft rejection was analyzed, as was the role of both factors in the evolution and survival of the graft. The study included 22 patients treated with Cyclosporin A (CsA) and 22 patients treated with Azathioprine (AZA). Inflammatory infiltrate was studied by immunostaining with a panel of monoclonal antibodies, and CMV DNA was detected by in situ hybridization on tissue sections. In patients treated with CsA, increased cellularity was found at both glomerular and interstitial levels, consisting mainly of macrophages and T-cells, which was consistent with the higher rate of glomerulointerstitial rejection found in this group. In contrast, the vascular type of rejection predominated in AZA treated patients. However, the presence of CMV DNA did not influence the phenotype of the inflammatory infiltrate, and was not associated with any specific lesion. Furthermore, the final outcome of the renal graft was independent of the detection of CMV. Therefore, this study provides no evidence of any active role of the CMV genome in renal graft rejection, and suggests that therapy should be adapted to the type of rejection as defined on morphologic and immunophenotypic grounds.
This work investigates how thymic dysfunction contributes to the depression of cell-mediated immunity in protein-energy malnutrition (PEM). In Bolivian children hospitalized for severe PEM, the size of the thymus was measured by echography, and the lymphocyte subpopulations were detected by using monoclonal antibodies. These data were compared with those obtained from healthy control subjects. Regardless of the clinical form of PEM, our results show a high degree of T lymphocyte immaturity in severely malnourished children, which correlates with a severe involution of the thymus. Before in vitro incubation with thymulin, this significant increase in the percentage of circulating immature T lymphocytes was concomitant with a decrease in mature T lymphocytes and a slight increase in cytotoxic T subpopulations. After in vitro incubation with thymulin, immature T lymphocytes decreased and mature T lymphocytes increased.
Three secondary human yolk sacs (SHYSs) showing heterotopic endodermal tubular structures of the gut-forming type were analyzed from a series of 180 SHYSs. These structures were similar to the early somatic endoderm involved in the formation of gut and lung. They may have arisen either as sequestrations in growth-disorganized embryos or as a phenomenon of differentiation from extraembryonal endoderm, which would indicate that extraembryonal tissues such as the SHYSs retain the capacity to differentiate somatic endoderm in developmentally altered embryos. It is possible that these structures may be the precursors of placental hepatic tissue and teratomas. Their morphologic resemblance to similar structures found in glandular, polyvesicular, and intestinal human yolk sac tumors provides yet another example of the similarity between SHYSs and yolk sac tumors.
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The results of extracorporeal lithotripsy on 250 patients with renal and ureteral stones are reported. Stone size varied from less than 1 cm (64%), 1 to 2 cm (31%) to over 2 cm (4%). 51% of patients were treated on an ambulatory basis. Complete fragmentation was obtained in 97% of patients and 78% were free of any demonstrable stone after 90 days. lithotripsy is an effective procedure allowing ambulatory non surgical treatment of urinary stones in many patients.
Two hospital-made, lactose-free, hypoosmolar formulas were compared for therapy for 61 children aged 10-28 months who had severe malnutrition and protracted diarrhea. The formulas were isocaloric and contained dextrin-maltose, carrots, sunflower oil, minerals, and vitamins. One had chicken meat as the protein source and the other had hydrolyzed lactalbumin (LAD). Initially the formulas were given as a continuous enteral feeding by nasogastric tube and pump. Six patients died from metabolic and infectious complications: four failed to equilibrate and changed diet. The remaining 51 were divided into two groups; group A, chicken formula (n = 26), and group B, LAD formula (n = 25). The mean duration of diarrhea was similar in both groups; number of days with liquid stools = 6.0 +/- 4.1 in group A, 5.5 +/- 2.8 in group B; number of days with greater than 4 stools/day = 3.5 +/- 3.4 in group A, 4.1 +/- 2.1 in group B. The time until beginning nutritional recovery was 13.2 +/- 12.0 days in group A and 13.3 +/- 7.8 days in group B. Intercurrent infections were significantly more frequent in patients receiving chicken formula (12 of 30 patients) than in those receiving LAD formula (4 of 27 patients) (p less than 0.05). We conclude that chicken formula is an efficient substitute to expensive semielemental formulas for continuous enteral feeding of protracted diarrhea in severely malnourished children.
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The pathology of cardiac xenografts has yielded critical insights into the mechanisms of xenograft rejection and the therapeutic procedures that might be applied to preventing or treating it. The conditions seen in rejecting cardiac xenografts include hyperacute rejection, acute vascular rejection, and cellular rejection. Hyperacute and acute vascular rejection of cardiac xenografts have features typical of humoral injury. Less is known about cellular rejection and only speculation can be offered about chronic rejection. Still, these features allow critical testing of pathogenetic mechanisms and therapies.