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Biomedical subjects

M A Weiss

Publications and source records attributed to M A Weiss.

At least 181 records · Page 10Linked to original sources

Proteinuria following transplantation. Correlation with histopathology and outcome.

A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3--membranous glomerulopathy, 2--focal sclerosis and hyalinosis, 1--membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3--chronic rejection; 2--membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18 patients who retained their grafts, 8 had glomerulonephritis, 5 transplant glomerulopathy, and 5 chronic rejection. This study confirms the poor prognosis that has been reported with the development of nephrotic-range proteinuria in renal allograft recipients.

Graft Survival↗

Solution NMR studies of intact lambda repressor.

Using a combination of two and one-dimensional NMR spectroscopy, it is shown that in the intact bacteriophage lambda repressor, the N-terminal domain assumes the same global structure as when it remains isolated. It is further shown that the N-terminal domain is only loosely attached to the C-terminal domain in the intact repressor.

DNA-Binding Proteins↗

Mechanisms of suppression of mouse mesangial cell proliferation by macrophage supernatants.

The monocyte/macrophage has been identified as an effector cell infiltrating the glomerulus in human and experimental nephritis. To clarify the role of the macrophage in this context, an in vitro system was developed in which mouse mesangial cell cultures were maintained. Macrophage supernatants were obtained from peritoneal macrophages harvested from either resident or endotoxin-stimulated C57BL/6J male mice cultured for 24 hr. Incubation of mesangial cell cultures with macrophage supernatants resulted in depression of mesangial cell metabolism as indicated by incorporation of (3H)-thymidine; the effect was more marked when supernatants of endotoxin-treated mice were used. The molecular mechanisms by which suppression was obtained was clarified by experiments fractionating macrophage supernatants by G-100 column chromatography. By this means, two fractions were obtained with different molecular and physiologic properties. One fraction, a molecular size of 14,600 to 29,000 daltons, was shown to mediate the suppressive effect by stimulating endogenous mesangial cell PGE synthesis; additionally, a novel molecular species was identified, which was biologically active at higher concentrations of macrophage supernatants, had a larger molecular size (29,000 to 68,000 daltons), exerted its suppressive effect by an independent mechanism, and accounted for the inability of indomethacin pretreatment of mesangial cells to abrogate completely the suppressive effect of macrophage supernatant at higher concentrations.

Animals↗

Deficiency of a plasma factor stimulating vascular prostacyclin generation in patients with lupus nephritis and glomerular thrombi and its correction by ancrod: in-vivo and in-vitro observations.

Glomerular thrombi occur frequently in active lupus nephritis. Their presence has been correlated with low platelet counts and with subsequent development of glomerular sclerosis. We have examined the plasma PGI2 generating capacity of 8 patients with active lupus nephritis with thrombi that were to undergo defibrination therapy with ancrod. PGI2 generation by these plasma samples was significantly decreased as compared both to normals and to 6 individuals with lupus nephritis and no glomerular thrombi. Significant improvement in the capacity to generate PGI2 was seen in the post-ancrod treatment plasma samples. the pathogenesis of this defect is discussed.

Ancrod↗

Evaluation of the peroxidase-antiperoxidase method for demonstrating cell membrane B2-microglobulin.

The peroxidase-antiperoxidase (PAP) immunohistochemical technic was evaluated for its usefulness in studying B2-microglobulin (B2m) expression in the cell membrane of human tumor lines grown in athymic mice. Eleven human tumor xenograft lines expressing various amounts of B2m were used. B2m was assessed by three methods: PAP technic on formalin-fixed, paraffin-embedded tissue; indirect immunofluorescence on frozen sections; and radioimmunoassay on soluble tumor extracts. The three technics gave comparable results, and the PAP technic proved to be useful in evaluating B2m.

Animals↗

Defibrination with ancrod in glomerulonephritis: effects on clinical and histologic findings and on blood coagulation.

Ancrod, which produces in vivo defibrination, has been shown to improve renal function and decrease fibrin deposition and crescents in experimental glomerulonephritis. Ancrod was given for 14 days to 5 patients with glomerulonephritis, moderate to severe renal functional impairment, crescents, and/or fibrin deposition in glomeruli. 4 patients had systemic lupus erythematosus. Ancrod treatment resulted in fibrinogen levels less than 50 mg/dl without bleeding, decrease of previously elevated factor VIII and von Willebrand factor levels, and normalization of in vitro platelet hyperaggregation. Renal function improved in all 5 patients. Serial renal biopsies showed a relatively rapid decrease of glomerular thrombi and necrosis and little increase in glomerular sclerosis. Ancrod administration appears safe, and may have a role in treatment of certain types of glomerulonephritis.

Adolescent↗

Wegener's granulomatosis: prolonged patient survival after pneumonectomy and renal transplantation.

Wegener's granulomatosis was diagnosed in a 42-year-old female 16 years ago. From the outset there was upper respiratory, pulmonary, and renal involvement. Over the years she received varying combinations of glucocorticoids and azathioprine. Renal function deteriorated, and she was treated by hemodialysis and living related donor transplantation 9 and 10 years, respectively, after the onset of the disease. 3 months prior to transplantation, the patient had a right pneumonectomy for bronchial stenosis, bronchiectasis and repeated sepsis. 5 years' posttransplantation, she is well and has no signs of activity of original disease.

Adult↗

Successful treatment by defibrination with ancrod in a patient with hyperacute renal allograft failure and a deficiency of plasma prostacyclin stimulating factor.

Hyperacute and renal allograft failure, whether due to rejection or other mechanisms, such as perfusion injury, is usually associated with extensive intraglomerular fibrin deposition and allograft loss. Defibrination with ancrod was used to treat a patient with hyperacute renal allograft failure and extensive glomerular fibrin deposition and necrosis. The patient's plasma had normal fibrinolytic activity but a complete absence of the ability to generate prostacyclin-like activity from rat aortic endothelium "in vitro". Treatment was associated with complete recovery of renal function, disappearance of glomerular fibrin, and restoration toward normal of glomerular structure.

Adult↗

Midline granuloma syndrome: a clinicopathologic study of 13 patients.

Thirteen patients with the clinical features of the midline granuloma syndrome are reported. Seven of the patients were determined to have Wegener's granulomatosis and had segmental necrotizing glomerulonephritis in their renal biopsies. Eighteen upper aerodigestive trace mucosal biopsies were available for review from the seven patients, and nine of these biopsies had a granulomatous angiodestructive inflammatory cell infiltrate considered "diagnostic" of Wegener's granulomatosis. The remaining nine biopsies lacked the specific histologic features of Wegener's granulomatosis but were considered consistent with mucosal involvement by the disease. Five of the remaining six patients had upper aerodigestive tract biopsies that were characterized by lymphocytic infiltrates. Three of the five patients had appreciable numbers of "atypical" cells in their biopsies and presented with radiologic evidence of lung involvement. It is our impression that patients with "significant cellular atypia" in their lymphocytic infiltrates have a disease indistinguishable from lymphomatoid granulomatosis, and these patients have a high propensity for either the presence or development of systematic disease that may require chemotherapy. Two patients had lymphocytic infiltrates with only minor degrees of cytologic atypia and no evidence of multisystem disease, and both of these patients responded to local radiation therapy. The remaining patient had a nonspecific histologic pattern in her numerous biopsies and was diagnosed as idiopathic midline destructive disease. She also had an adequate response to radiation therapy.

Adult↗

Transurethral resection of the prostate with partial resection of the seminal vesicle.

A retrospective study was done on 185 patients who underwent transurethral prostatectomy. Of these patients 6 had seminal vesicle tissue in the resected specimen. The presence of the yellow-brown pigment, lipofuscin, in the seminal vesicle epithelium was a consistent finding and, often, paramount to differentiation from carcinoma of the prostate. There was no pathological misdiagnosis of malignancy in this series. Of the 6 patients 2 suffered acute epididymitis postoperatively and 1 had persistent microscopic hematuria 2 months postoperatively. The high incidence of postoperative epididymitis probably is owing to contamination of the seminal vesicles by bacteria. Acquired during urinary tract manipulation, having access to the seminal vesicles and, thus, the vas deferens. In these patients vasectomy and broad-spectrum antibiotics are recommended because epididymal invasion by bacteria may already have occurred before pathologic diagnosis is obtained.

Epididymitis↗

Sclerosing peritubular nodules: a hereditary renal abnormality in von Recklinghausen's disease.

A previously unrecognized type of renal lesion characterized by the formation of multiple hamartomatous sclerosing peritubular nodules in the cortex is described. These lesions were hereditary, appearing in three members of a family, which included the mother and her two sons, in association with familial central von Recklinghausen's disease (bilateral acoustic schwannomas). The nodules originated as concentric peritubular proliferations of collagen producing spindle cells, which ultrastructurally showed myofibroblastic differentiation. Four stages of nodule development leading to progressive sclerosis and tubular destruction are described. In spite of widespread involvement of the cortex with numerous nodules, in none of the three patients was there any clinical manifestation of renal dysfunction or hypertension.

Adult↗

Heterogeneity of beta 2-microglobulin in human breast carcinoma.

beta 2-microglobulin (beta 2m) content and distribution in human benign and malignant breast tissues have been investigated by immunohistologic means, and wide differences in the expression of this protein have been observed. The distribution of beta 2m as determined by indirect immunofluorescence was uniform throughout normal human and benign breast tumor tissues, as well as in human tumor xenografts grown in athymic mice, but marked difference in beta 2m content was demonstrated between individual tumors. In breast carcinomas, heterogeneity in beta 2m expression was found to exist within individual tumors. This heterogeneity was evident mainly in moderately well-differentiated tumors; the majority of poorly differentiated tumors did not express beta 2m at all. It is suggested that the expression of surface beta 2m is an indicator of tumor cell differentiation or maturation.

Animals↗