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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 199 records · Page 11Linked to original sources
PubMed1975

Human glomerular cells in tissue culture.

Cells from human glomeruli explanted in tissue culture were grown and subcultivated up to 12 to 13 times. Light and electron microscopic studies revealed these cells to be morphologically distinct from fibroblasts. By electron microscopy, an extracellular material resembling basal lamina was seen and prominent intracellular microfilaments were evident. Immunofluorescent microscopy demonstrated reactivity of heterologous antiglomerular basement membrane antibody with aggregates of extracellular material. Absorption experiments using antiglomerular basement membrane antibody showed that the extracellular materiial shared some antigenic components with glomerular basement membrane. Antibody to cultured glomerular cells stained the mesangium and glomerular basement membrane of normal human kidney. This antibody was nephrotoxic in monkeys, induced proteinuria with proliferative glomerulonephritis, and localized to the mesangium and glomerular basement membrane of monkey glomeruli. These findings and the presence of prominent intracellular microfilaments (contractile elements) suggest that the glomerular cells may be of mesangial origin.

Adult↗
PubMed1975

Studies of the alternate pathway in chelated serum.

Activation of the alternate pathway in chelated serum by cobra venom factor (Co F), endotoxin of Escherichia coli, inulin, and zymosan was studied by immunoelectroprhoresis, radial immunodiffusion, and complement fixation tests. In serum chelated by 10 mM EGTA and 10 mM MgCl-2 (10 mM MgEGTA) activation by the classical pathway was blocked, but activation of C3PA and C3 occurred normally. By radial immunodiffusion assay, consumption of C3 and properdin was demonstrated to be similar to consumption in nonchelated sera. By immunoelectrophoresis, C3PA and C3 were shown to be activated by CoF in serum chelated with 6 mM but not with 10 mM EGTA without added Mg++. Inulin and endotoxin did not result in activation of either C3PA or C3, while C3PA but not C3 was activated by zymosan in the presence of 10 mM EGTA without Mg++ added. Consumption of properdin and C3, measured by radial immunodiffusion, was inhibited by 6 to 10 mM EGTA following activation by inulin, but not following activation by zymosan. The usefulness of 10 mM MgEGTA-chelated serum for the selective investigation of the alternate pathway in chemotaxis was demonstrated.

Blood Protein Electrophoresis↗
PubMed1975

The secretory immune system and renal disease.

An immunopathological analysis of renal tissue from 105 patients was undertaken: (1) to clarify the relationship of the secretory immune system to renal diseases in which glomerular deposits of immunoglobulin A, (alpha chain), occurred; (2) to determine the lower nephron localization of secretory component and alpha chain in renal disease. This study, which included twenty-four patients with glomerular deposits of alpha chain, failed to reveal glomerular localization of secretory IgA. Secretory component was not found in renal tubular cells in kidneys with normal or minimally abnormal renal histology. In contradistinction to these findings, significant amounts of secretory component were found in tubular epithelial cells and casts in tissue from fifty-one patients with morphological evidence of significant renal damage; this localization had no correlation with glomerular deposits of IgA, IgM or other immunoreactants. Alpha Chain was rarely found in the tubular epithelium or in interstitial round cells; fifteen patients had alpha chain in casts. We conclude that the glomerular localization of immunoglobulin in glomerulonephritis is not derived from the secretory immune system, and the IgA present in glomeruli is not secretory IgA. The finding of secretory component in tubular cells in diseased kidneys without alpha chain may support an hypothesis for an independent role for secretory component in renal disease, apart from its function in the transport and stabilization of secretory IgA.

Adolescent↗
PubMed1974

Renal transplantation in diabetes mellitus in rats.

Immunoglobulins and complement are deposited in the glomerular mesangium of rats with progressive glomerulosclerosis secondary to chemically induced diabetes mellitus. Isotransplantation of a kidney from a rat diabetic for 6 mo into a normal recipient results within 2 mo in the disappearance of IgG, IgM, and beta(1)C from the mesangium and arrest or reversal of the light microscopic glomerular lesions. Kidneys isotransplanted from normal donors into diabetic rats developed mesangial matrix thickening and deposition of IgG, IgM) and beta(1)C in the mesangium. No glomerular changes occur upon transplantation of a normal kidney into a normal rat. These findings indicate that diabetic glomerular changes in the rat are reversible and are secondary to the diabetic state rather than to the inducing agent.

Animals↗
PubMed1974

The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.

These studies were designed to explore the effects of nephrotoxic serum (NTS) in rats on the uptake and processing by the glomerular mesangium of intravenously administered protein macromolecules (radiolabeled aggregated human IgG, [125I]AHIgG). Measurements of [125I]AHIgG levels in preparations of isolated glomeruli correlated well with qualitative estimates of glomerular IgG deposition seen by immunofluorescent microscopy. Rats given 2 ml NTS received 25 mg/100 g body wt [125I]AHIgG 48 h later and were sacrificed at varying time intervals thereafter. NTS-treated animals demonstrated a marked increase in glomerular uptake of [125I]AHIgG as compared with concurrent controls but a normal ability to clear [125I]AHIgG from the mesangium over 72 hr. Animals given 1.0, 0.5, and 0.25 ml NTS had neither proteinuria nor significant light microscopic changes, yet had increased uptake of [125I]AHIgG of 4.4, 3.0, and 2.1 times control values, respectively at 8 h after the infusion of aggregates. Rats given 1 ml NTS and 12.5, 6.25, and 3.125 mg [125I]AHIgG/100 g body wt had increased glomerular uptake at 8 h, but there was, within both NTS and control groups, a disproportionate decrease in uptake at lower [125I]AHIgG doses. Rats given cobra venom factor (CoF) followed by a NTS shown to be complement dependent (proteinuria reduced by prior complement depletion with CoF) had less mesangial [125I]AHIgG uptake than NTS controls but greater uptake compared with normal controls. CoF itself had no effect on mesangial or reticuloendothelial system [125I]AHIgG uptake. These studies demonstrate a striking change in glomerular mesangial activity after fixation of nephrotoxic antibodies to the glomerular basement membrane, even in the absence of proteinuria and suggest that subtle alterations of the filtration surface can influence mesangial function. The effect of NTS on the mesangium is due, in large part, to the glomerular injury and proteinuria which nephrotoxic antibodies produce.

Animals↗
PubMed1974

Immunofluorescent localization of antihemophilic factor antigen and fibrinogen in human renal diseases.

Tissue localization of antihemophilic factor (AHF, factor VIII) antigen and fibrinogen by immunofluorescent microscopy was determined in 146 specimens of normal and diseased kidneys. AHF antigen was present in the endothelial cells of glomeruli, peritubular capillaries, arteries, and veins of normal kidneys; a distribution similar to that in other tissues. In scleroderma and malignant hypertension, deposition of AHF antigen and fibrinogen was limited to the markedly thickened endothelial layers of arteries. More extensive intense deposition of both AHF antigen and fibrinogen in glomeruli and in arterial walls were present in hyperacute renal homograft rejection, hemolyticuremic syndrome, postpartum renal failure, and in some cases of acute homograft rejection. In contrast, deposition of fibrinogen was observed in glomerular epithelial cresents in severe proliferative glomerulonephritis, but AHF deposition was not present in these lesions. Glomerular deposition of fibrinogen without increased AHF standing was also detected in renal tissue from patients with anaphylactoid purpura nephritis and in recurrent macroscopic hematuria with focal glomerulonephritis. Increased staining of peritubular capillaries with anti-AHF was seen in diseased kidneys irrespective of etiology. Immunofluorescent localization of AHF, a participant in the intrinsic coagulation pathway, offers a new way by which to analyze the mechanisms responsible for fibrinogen deposition in disease.

Arteries↗
PubMed1974

The immunohistopathology of glomerular antigens. The glomerular basement membrane, collagen, and actomyosin antigens in normal and diseased kidneys.

The immunofluorescent localization of antisera to human glomerular basement membrane (GBM), collagen, and smooth muscle actomyosin was examined in 15 specimens of normal renal tissue and 98 specimens from patients with renal disease. The anti-GBM and anticollagen antisera normally localize to GBM, while antiactomyosin localizes to the mesangium. Diabetic nephropathy revealed a striking expansion of mesangial material reacting with antiactomyosin. In contrast, the expanded mesangium in membranoproliferative glomerulonephritis did not react with antiactomyosin, and the GBM localization of anti-GBM and anticollagen sera was similarly lost. The thickened GBM in diabetes mellitus and membranous nephropathy reacted with anti-GBM and anticollagen, but with accentuation of staining on the inner aspect of the GBM. In proliferative glomerulonephritis there was a moderate increase in the distribution of actomyosin. Glomerular sclerosis and hyalinization in all diseases studied was accompanied by a loss of immunofluorescent staining for all glomerular antigens, including collagen.

Actomyosin↗
PubMed1974

Hematogenous Streptococcus faecalis pyelonephritis in the rat. A histologic, immunopathologic and bacteriologic study.

The demonstration of bacterial antigens in active pyelonephritis in man has been inconsistent. In this paper we have studied 110 rats with experimental pyelonephritis induced by a single intravenous injection of Streptococcus faecalis. The animals were studied at intervals up to 1 year; bacteremia, urine and renal parenchymal bacterial counts were monitored. In these animals it was observed that bacteriuria and positive bacterial cultures of renal tissue persisted up to 1 year in some rats. Bacteria and their antigenic products in small foci were detected by immunofluorescence in the pyelonephritic lesions. The highly focal distribution of the bacterial antigens in bacteriologically positive tissues of this model suggest the need for careful fixation technics, availability of large tissue specimens and careful control of immunologic factors. These specific requirements to detect bacterial antigens may preclude the practical study of human pyelonephritic kidneys.

Animals↗
PubMed1974

The nail-patella syndrome-pathogenesis of the kidney lesion.

The nail-patella syndrome is an inheritable disorder of connective tissue in which multiple osseous abnormalities are frequently associated with renal dysfunction and proteinuria. This paper describes a unique abnormality of glomerular basement membranes (GBM) in eight patients. The abnormality consists of fibrils and bundles of cross-striated collagen within the GBM of each patient, including children with minimal proteinuria. This ultrastructural lesion may provide increased understanding of the pathogenesis of the basic defect underlying both the osseous and renal lesion.

Basement Membrane↗
PubMed1974

Failure of cobra venom factor to prevent the generalized Shwartzman reaction and loss of renal cortical fibrinolytic activity.

Previous studies have shown that renal cortical fibrinolytic activity is absent in rabbits given one or two injections of endotoxin. Using a fibrin slide technic, we have studied the effect of endotoxin on cortical fibrinolytic activity in rabbits depleted of terminal complement components (C3-C9) by cobra venom factor. The loss of cortical fibrinolytic activity induced by endotoxin is not prevented by pretreatment with cobra venom factor. Additionally, this complement depletion did not prevent development of glomerular fibrin deposition, cortical necrosis or thrombocytopenia in the generalized Shwartzman reaction.

Animals↗
PubMed1974

Glomerular fibrinolytic activity following endotoxin-induced glomerular fibrin deposition in the pregnant rat.

The effect of endotoxin on glomerular fibrinolysis in pregnant and nonpregnant rats was studied using a fibrin slide technic. Glomerular fibrinolytic activity was present and light microscopy was normal following endotoxin or saline injection in nonpregnant rats. In pregnant rats, fibrin was regularly detected within glomerular capillaries 2 hours following administration of endotoxin but was completely removed within 48 hours. Glomerular fibrinolytic activity was present throughout this time interval. These studies suggest that glomerular fibrinolytic activity plays an important role in the removal of glomerular fibrin.

Animals↗
PubMed1973

The glomerular mesangium. 3. Acute immune mesangial injury: a new model of glomerulonephritis.

A mechanism of immune glomerular injury is described based on the fixation of antibody (Ab) to an antigen (Ag) that has localized in the glomerular mesangium. Rabbits were given, intravenously (i.v.), aggregated human IgG (AHIgG) or albumin (AHSA) and 10 h later, when the Ag by immunofluorescent microscopy was present in the mesangium, a kidney was removed and transplanted into a normal rabbit. The recipient then received, i.v., rabbit anti-HIgG or anti-HSA. Within minutes of Ab infusion, glomeruli of the donor kidney had polymorphonuclear (PMN) infiltration that over the next few hours became marked and was associated with glomerular cell swelling. At 24 h a decrease in PMN's and early mesangial proliferation was seen. By 3 days there was marked mesangial hypercellularity and increased mesangial matrix. Within minutes after Ab administration rabbit IgG, C3, and fibrin were seen in the glomerular mesangium. There was a fall in complement titer by 1 min after Ab infusion that was due to complement consumption by the donor kidney. Complement then returned to normal levels by 48 h. Significant glomerular injury did not occur (a) in the recipient's own kidney, (b) from Ag administration and transplantation without recipient Ab administration, or (c) from transplantation and Ab administration without prior Ag administration. These studies demonstrated that Ag localized in the glomerular mesangium can react with circulating Ab and complement resulting in severe glomerular injury.

Animals↗