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Biomedical subjects

F Sanfilippo

Publications and source records attributed to F Sanfilippo.

At least 163 records · Page 9Linked to original sources

The possible occurrence of staphylococcal postinfectious glomerulonephritis in a renal allograft.

A 38-year-old male with a 5-year history of dialysis-dependent renal failure secondary to membranoproliferative glomerulonephritis, type I, received a cadaveric renal allograft from a 51-year-old male dying from acute trauma. A pretransplant biopsy of the donor kidney revealed no glomerular disease. One month after transplantation, the patient was discharged with a stable creatinine of less than 2.0 mg/dl, but subsequently developed positive urine cultures for Staphylococcus aureus and Escherichia coli and eventually underwent transplant nephrectomy. Blood cultures were positive postoperatively for S. aureus, and examination of the transplant nephrectomy showed ultrastructural, histological, and immunofluorescent findings characteristic of postinfectious glomerulonephritis. While numerous types of glomerular disease have been reported in kidney transplants, this report represents the first case suggestive of bacterial postinfectious type glomerulonephritis we have seen occurring de novo in a renal allograft.

Adult↗

Immunobiology of primary intracranial tumors. Part 8: Serological responses to active immunization of patients with anaplastic gliomas.

Serial serological studies were carried out on 19 of 20 patients with malignant gliomas who were actively immunized with one of two human glioma tissue culture cell lines (D-54MG or U-251MG). Most patients mounted a significant serum reaction to histocompatibility antigens (HLA's), as well as an antibody response to fetal bovine serum (FBS) which was added to the glioma-cell inoculum. These two sources of antibody accounted for greater than 90% of the antibody induced by these inoculations. Two patients continued to have significant amounts of binding antibody to the original immunizing cell line following exhaustive absorptions of FBS and these two had all remaining significant antibody removed by further absorption of the serum against the 2-T osteogenic sarcoma tissue culture cell line known to possess antigens cross-reactive with human gliomas. One single patient continued to show significant antibody binding to the original glioma cell line following absorption against FBS, human platelets, and the 2-T cell line, and therefore seems to have produced glioma-distinctive antibodies in response to immunization. The antibody preparation from this patient was also cytotoxic against the original glioma cell line, as well as another recently cultured human glioblastoma cell line. The significance of these serological studies is discussed as it relates to immunological responses patients with gliomas may make to active immunization.

Antibodies, Anti-Idiotypic↗

IgA nephropathy. Correlation of clinical and histologic features.

The clinical and histologic features of 81 patients with IgA nephropathy were analyzed. Azotemia was present in 32 per cent of the patients, proteinuria was present in 88 per cent, and gross or microscopic hematuria was present in all of the patients tested. The median age of histologic diagnosis was 27 years. The median age at onset of clinical signs was 20 years. There was no increased incidence in any HLA-A or -B antigen within the patient population over our control population. All patients had glomerular mesangial IgA deposition (by definition) greater than or equal to IgG or IgM. Histologic changes were quantitated and ranged from normal to necrotizing and/or crescentic glomerulonephritis. Many patients (48 per cent) had mild or moderate generalized glomerlular hypercellularity. Nonparametric statistical analysis showed strong correlations among patient age at histologic diagnosis, creatinine, proteinuria, global glomerular sclerosis, and interstital fibrosis. Our analysis suggests that IgA nephropathy is an indolent disease generally beginning in childhood. It is a cause of renal insufficiency in a significant number of patients. Interpretation of this series and other reported studies suggests that most cases of IgA nephropathy in the United States are best considered idiopathic but that hereditary and secondary forms may exist.

Adolescent↗

Beneficial effects of histocompatibility in high-risk corneal transplantation.

Forty-six consecutive patients at high risk for corneal graft rejection because of significant vascularization or previous graft rejection received transplanted corneas from donors who were selected on the basis of a negative lymphocyte crossmatch, ABO antigen blood group compatibility, and maximized HLA-A and HLA-B antigen matching. Graft survival in this study group was compared to that in a retrospective control group of 71 consecutive high-risk transplants performed in patients receiving corneas obtained randomly. We found no differences between groups in terms of demographic factors, cause of primary corneal disease, or the incidence of previous graft rejection. However, graft survival in the control group was only 49% (35 of 71) vs 83% (38 of 46) for the study group (P less than .001) with mean follow-up times of 29.6 and 15.5 months, respectively. All graft failures in the study group were in recipients with poorly matched HLA antigens. Patients with evidence of humoral presensitization to HLA antigen had twice the rejection rate of unsensitized recipients (three of 11 vs five of 35).

ABO Blood-Group System↗

Fate of four cadaveric donor renal allografts with mesangial IgA deposits.

In the course of routine pretransplant cadaveric donor kidney biopsy examination, specimens from two donors were found to exhibit intense mesangial localization of IgA by immunofluorescence, with the presence of large immune complex-type deposits in these areas confirmed ultrastructurally. Both kidneys from each donor were transplanted with the ultimate result that three of the four kidneys underwent early irreversible rejection and were removed within 3 months, while the fourth kidney has maintained normal function for a period of 8 months. Morphological and immunofluorescent evaluation of the rejected kidneys at the time of nephrectomy showed minimal residual IgA mesangial deposits, but all had changes indicative of severe acute allograft rejection. These findings suggest that glomerular lesions involving mesangial IgA deposition can resolve fairly quickly following transplantation, but that the risk of irreversible acute rejection might be greater in the recipients of such kidneys.

Adult↗

Immunohistochemical studies of cell differentiation in a juxtaglomerular tumor.

A renal tumor removed from a 29-year-old woman, who recently had had onset of primary hypertension, showed the histologic and ultrastructural features of a renin-secretory juxtaglomerular cell tumor. The expression of Factor VIII-related antigen (FVIII-RAG) was evaluated to identify endothelial differentiation of tumor cells in this lesion. Control tissue and vessels within the tumor showed normal expression of FVIII-RAG, but tumor cells as well as normal juxtaglomerular cells showed no localization of this antigen, which suggests the nonendothelial nature of these specialized cells.

Adult↗

Immunotherapy of murine leukemia. V. Protection against Friend leukemia virus-induced immune complex glomerulonephritis by passive serum therapy.

The development of immune complex glomerulonephritis in DBA/2 mice infected with Friend murine leukemia virus (F-MuLV) was compared with that in mice protected against virus-induced disease by administration of chimpanzee anti-F-MuLV antiserum (CaF-MuLV). Morphologic analysis of glomeruli from viremic (infected) normal chimpanzee serum-treated animals revealed significant renal disease within 2 weeks following virus inoculation, with glomerular immune complex deposits and C-type viral particles seen by electron microscopy. Localization of F-MuLV envelope and core antigens (gp71 and p30, respectively) was also detected by immunofluorescence, as was murine IgG and C3. However, age-matched DBA/2 mice treated with CaF-MuLV antiserum alone or following F-MuLV inoculation showed no evidence of systemic disease and neither localization of F-MuLV antigens nor detectable virus particles. These data indicate that in addition to erythroleukemia, F-MuLV infection results in severe immune complex glomerulonephritis and that passive immunotherapy can protect susceptible mice from both aspects of viral pathogenesis.

Animals↗

Crystalline deposits of calcium and phosphorus: their appearance in glomerular basement membranes in a patient with renal failure.

The kidneys and lungs of a 71-year-old man with a 30-month history of biopsy-proven Wegener's granulomatosis were examined at autopsy. They displayed striking crystalline deposits in glomerular basement membrane (GBM) and, to a much lesser extent, other basement membranes. The patient had been in renal failure, with peritoneal dialysis instituted three weeks before death. Energy-dispersive x-ray microanalysis of these deposits showed them to consist of calcium and phosphorus. Transmission electron microscopy revealed their presence diffusely throughout all layers of GBMs, with focal areas showing early reactive membrane formation. Control studies confirmed these deposits as being an endogenous, in vivo phenomenon, representing a morphologic finding not previously described to our knowledge.

Acute Kidney Injury↗

The induction of carrier-specific helper cell tolerance in presensitized rats.

Lewis rats rendered tolerant to sheep IgG (SGG) show a markedly reduced antibody response to the 2,4,6-trinitrophenyl (TNP) hapten when later challenged with TNP-SGG. We have previously shown that this effect is due to functional unresponsiveness in the carrier SGG-specific helper T cell population. In this paper we demonstrate that induced helper cell tolerance is also maintained through a secondary immunogenic challenge. Furthermore, rats which are primed to the carrier SGG prior to tolerance induction also show a markedly reduced anti-TNP response upon secondary immunogenic challenge with TNP-SGG. The ability to specifically suppress a secondary response in this manner was found to be relatively long lasting, since rats showed reduced responsiveness when the secondary challenge was delayed for up to 4 weeks after tolerance induction. In addition, rats primed to the hapten (TNP) prior to carrier (SGG) tolerance induction also showed a marked reduction in anti-TNP antibody following challenge with TNP-SGG. These findings imply that helper cell tolerance can be induced in rats even after priming of carrier-specific (SGG) helper cells, or hapten-specific (TNP) B cells. These results parallel our other published findings that IgE responses in presensitized rats can be overcome by helper cell tolerance.

Animals↗

Effect of carrier-specific tolerance on the generation of helper cell function.

The effect of carrier-specific tolerance on the development of helper cell function was studied in irradiated rats reconstituted with normal or carrier-tolerant bone marrow. Bone marrow (BM) from normal rats or rats tolerant to sheep IgG (SGG) was transferred to lethally irradiated syngeneic recipients, which were challenged 3 to 5 weeks later when immunocompetence to T-dependent antigens was shown to have recovered. When recipients were challenged with the 2,4,6-trinitrophenyl (TNP) hapten coupled to SGG in adjuvant, groups which received SGG-tolerant BM were 70-80% unresponsive in terms of anti-TNP plaque-forming cells compared to recipients of normal BM. This effect was carrier (SGG)-specific and was reversed when normal thymocytes were transferred with tolerant BM. Moreover, neither tolerant BM nor tolerant thymocytes were able to suppress the responsiveness of normal BM at a 1:1 ratio. These cell-mixing experiments imply that the reduction in helper cell function is due neither to suppressor cells nor antigen carryover in the tolerant BM. It is suggested that a BM precursor of the helper T cell may be rendered tolerant and therefore already possesses antigen specificity prior to thymic migration.

Animals↗