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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 181 records · Page 10Linked to original sources
PubMed1977

Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis.

An experimental model of focal sclerosis (FS) following chronic administration of aminonucleoside (AMNS) is described in rats with pathologic features similar to those observed in human steroid-resistant idiopathic nephrotic syndrome. Six groups of rats were given intraperitoneal injections of either 0.9% normal saline or aminonucleoside (13 mg. per 100 gm. of body weight); four groups underwent a right nephrectomy on day 22; a second series of injections of saline or aminonucleoside were then administered to all six groups: group I (five animals), saline-saline; group II (10 animals), AMNS-AMNS; group III (10 animals), AMNS-nephrectomy-AMNS; group IV (five animals), AMNS-nephrectomy-saline; group V (five animals), saline-nephrectomy-AMNS; group VI (five animals), saline-nephrectomy-saline. A relationship between the percentage of glomeruli with focal sclerosis and the total amount of protein excreted during the course of the experiment was observed (r=0.80). An apparent threshold level of protein excretion essential for the development of FS was also noted in that all rats excreting greater than 2.2 integral units developed FS whereas those excreting less than this amount did not. The highest incidence of FS was seen in rats that had received AMNS after unilateral nephrectomy: 62% of glomeruli with FS in group III and 26% in group V; whereas no FS was seen in groups I and VI or in rats evaluated 7 to 23 days after a single injection of AMNS. These studies indicate a quantitative relationship between the breakdown in the permeability barrier to protein and the ultimate development of FS. The prior demonstration of epithelial cell alteration in acute AMNS disease and the morphologic changes presented in this and the subsequent paper (Velosa JA, Glasser RJ, Nevins TE, Michael AF: Lab Invest 36:527, 1977) support the concept that irreversible epithelial cell injury may be the primary event in the development of FS.

Animals↗
PubMed1976

Recurrence of membranoproliferative glomerulonephritis following kidney transplantation. Serum complement component studies.

Sixteen patients with membranoproliferative glomerulonephritis who required kidney transplantation because of renal failure were evaluated for evidence of recurrence of the original disease by serologic and morphologic studies. Of the 12 patients with transplant tissue available for study, seven showed membranoproliferative glomerulonephritis by light morphology. Four of these seven also had hypocomplementemia, and this hypocomplementemia was characterized by decreased serum CH50, C3 beta1A or C3-C9 but norma serum C1, C4 and C2 by hemolytic assay. Immunofluorescent microscopy demonstrated more intense glomerular deposition of C3 and properdin in the hypocomplementemic patients. Ultrastructural studies demonstrated intramembranous deposits typical of dense deposit disease in one patient who also had marked hypocomplementemia. One patient who had two transplant biopsies and persistent hypocomplementemia showed progression from predominantly mesangial glomerular changes to both capillary wall and mesangial abnormalities. This study has shown a high rate of recurrence of membranoproliferative glomerulonephritis in the transplanted kidneys. A high death rate was noted in persistently hypocomplementemic patients. The serum C profile in hypcomplementemic patients who received translants was similar to that seen before transplantation, but the signficance of this finding remains unknown.

Adolescent↗
PubMed1976

Extramembranous glomerulonephritis in childhood: relationship to systemic lupus erythematosus.

Extramembranous glomerulonephritis is an uncommon but distinct pathologic lesion in children. The diagnosis is established by the characteristic light, immunofluorescent, and ultrastructural abnormalities in renal biopsy specimens. This report describes seven of the ten children with this lesion studied in the past 11 years. Emphasis is given to the comparison of four children with idiopathic membranous glomerulonephritis with three others who presented with a nephrotic syndrome but subsequently developed evidence of systemic lupus erythematosus. Two of the latter three children, and three others with SLE and MGN not described in detail, demonstrated deposition of IgA by immunofluorescence along glomerular capillaries. Five of six children with SLE and MGN had microtubular structures in glomerular endothelial cells demonstrable by electron microscopy. These observations suggest that children with MGN require careful and continuing study for evidence of SLE.

Adolescent↗
PubMed1976

Immunopathology of renal extracellular membranes in diabetes mellitus. Specificity of tubular basement-membrane immunofluorescence.

This study documents the presence of marked immunofluorescence for IgG and albumin in renal extracellular membranes, especially tubular basement membranes (TBM), of patients with severe diabetic nephropathy. A comprehensive immunofluorescent analysis was carried out on kidney tissue from 83 patients--Group I: 24 living normal renal allograft donors and two infants less than one week of age. Group II: 24 patients with severe nephropathy who had juvenile onset of diabetes 16 to 30 years previously and who ranged in age from 20 to 47 years. Group III: 33 patients with severe kidney disease of varied etiologies with an age range of five to 63 years. The sections were assayed for a variety of proteins (immunoglobulins, complement components, and tissue antigens). Kidney sections of all patients with severe diabetic nephropathy were readily distinguished from kidneys of other patients and normals by the intense linear staining of the extracellular membranes, especially the tubular basement membrane for IgG and and albumin. Dual-labeled studies using FITC anti-basement membrane (BM) and tetramethyl rhodamine (TMR) antialbumin demonstrated localization of the albumin predominantly to the outer but also the inner TBM while the BM antisera reacted more intensely with the inner membrane. There is no evidence that an immunologic process is responsible for these findings. These immunofluorescent findings are specific for severe diabetic nephropathy and may reflect structural changes in the renal extracellular membranes that permit entrapment of serum proteins, possibly due to changes in permeability.

Adolescent↗
PubMed1976

Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus.

Kidneys of patients with severe diabetic nephropathy demonstrate marked linear immunofluorescent staining of extracellular membranes, including the tubular and glomerular basement membranes (TBM and GBM) and Bowman's capsule. Immunofluorescent studies were carried out on kidney tissue obtained from 12 diabetic and 17 nondiabetic patients from two to 12 years following renal transplantation. The frequency and intensity of SgG and albumin staining of these membranes were significantly greater in the diabetic than in the nondiabetic patients (P less than 0.0005). TBM, GBM, and Bowman's capsule staining did not occur in any of the seven kidneys studies at the time of their transplantation into diabetic recipients. Thus, the abnormalities leading to the deposition or trapping of proteins in renal extracellular membranes occur early after the placement of normal kidneys into the abnormal metabolic environment of the diabetic transplant recipient. The present study supports the concept that basement membrane alterations in diabetes are a consequence of the biochemical perturbations of diabetes rather than a separately inherited genetically linked disorder.

Albumins↗
PubMed1976

Immunopathology of the end-stage kidney. Immunoglobulin and complement component deposition in nonimmune disease.

Seventy nephrectomy specimens from patients with end-stage renal disease, four renal biopsies from patients with focal sclerosing glomerulonephropathy (FSGN) and normal renal function, and 17 control biopsies from normal renal allograft donors (Group I) were studied by immunofluorescence with respect to deposition of immunoglobulins and classic and alternative complement (C) pathway components. The end-stage kidneys were divided into three groups according to etiology: 16 patients with immune-mediated glomerulonephritis (Group II), 22 patients with congenital and/or familial renal disease (Group III), and 32 patients with systemic or primary renal disease in which an immune-mediated injury could not be established (Group IV). The pattern of immunoprotein deposition in glomeruli in Groups II, III, and IV, and in biopsies of patients with FSGN was similar: peripheral lobular, globular and/or granular, focal and segmental; it was limited to dying glomeruli or abnormal glomerular segments. A statistically significant correlation existed between the percent of properdin-containing glomeruli and the percent of glomeruli undergoing hyalinization in Groups II, III and IV (II, r=0.67; III, r=0.92; IV, r=0.78). No deposition was observed in normal or completely fibrotic glomeruli. In vitro heterologous complement fixation was demonstrated in 17/19 end-stage kidneys in a similar distribution. Early classic C components, C1q and C4, were detected in a somewhat higher frequency in Group II (14/16) than Group III (11/22) and Group IV (20/32) (Group II vs. III, P=.02 and II vs. IV, P=.07). C3 and properdin were detected in 77 to 100% of all 3 groups; in 18 patients, C3 and properdin were present without detectable C1q and C4. Immunoglobulins, primarily IgM, and components of the classic and alternative C pathways are regularly present in hyalinizing glomeruli irrespective of the etiology of the renal failure. These observations suggest that an immune process is operative in glomerular obsolescence regardless of the underlying etiology of the renal disease.

Adolescent↗
PubMed1976

Studies of diabetic nephropathy in animals and man.

Animal models of diabetes mellitus allow for the manipulation of the metabolic state and the performance of experiments that may shed light on the pathogenesis of diabetic nephropathy. Rats with long-standing chemically induced diabetes develop glomerular mesangial thickening and immunoglobulin and complement deposition. These glomerular changes are reversible on the transplantation of a kidney from a diabetic rat into a normal host and on cure of the diabetic state by pancreatic islet transplantation. Conversely, diabetic renal changes develop in normal kidneys transplanted into diabetic rats (within tow to four months) and humans (within two years). These studies suggest that nephropathy results from the diabetic state. The mesangium is thickened in diabetic rats, mice, and humans. In rats, mesangial function is the processing of macromolecules localized therein is disturbed in areas of mesangial pathology. The finding that glomerulopathy is accelerated in uninephrectomized diabetic rats and is retarded in rat kidneys "protected" by narrowing of the renal artery suggests that alterations in glomerular blood flow are related to the pathogenesis of diabetic glomerular damage. Marked hyperglycemia in animals and man leads to "glycogen nephrosis," which affects the distal tubule at the level of the macula densa of the juxtaglomerular apparatus (JGA). This could lead to disturbance of JGA blood pressure regulation. Disturned mesangial function may result from failure of macula densa cells to process macromolecules that have reached that site from the mesangium.

Animals↗
PubMed1976

Urinary kallikrein in experimental renal disease.

Urinary kallikrein excretion was studied in two types of experimentally induced renal disease: anti-glomerular basement membrane nephritis (20 rats) and aminonucleoside nephrosis (five rats) with appropriate controls (23 rats) for a period of 6 to 9 weeks following disease induction. In both models there was a prompt significant decrease (p less than 0.01 - 0.001) in urinary kallikrein excretion associated with proteinuria but unrelated to urinary sodium and potassium excretion and urinary volumes. In antiglomerular basement membrane nephritis the fall in kallikrein excretion occurred within the first 24 hours concurrent with the onset of proteinuria. In aminonucleoside nephrosis the decrease antedated the onset of proteinuria by 48 hours beginning within the first 24 hours following injection of the aminonucleoside. Kallikrein inhibitors were not demonstrable in the urines of diseased animals from either model. The mechanism of the decrease in kallikrein excretion in immune and nonimmune glomerular disease associated with proteinuria is unknown.

Animals↗
PubMed1975

Hereditary C2 deficiency: Genetic studies and association with the HL-A system.

Herediatary C2-deficiency has been shown to be transmitted asn an autosomal recessive characteristic. Recent evidence indicates that some genetic factors involved in the control of the complement (C) system in both man and mice are governed by genes localized within the major histocompatibility regionmthis study describes a large pedigree of the paternal family of a C2-deficient patient with systemic lupus erythematosusl It is shown that this condition is transmitted as an autosomal recessive trait, the heterozygous carriers having approximately half normal levels of C2. Furthermore, this trait was shown to be inherited in close linkage with an infrequent HL-A typw, 2,4A2. The maternal, C2-defective chromosome was shown to be transmitted by HL-AW10, W18 haplotypemthis same haplotype was described in a similar study by Fu et al. (6) to be associated with C2 deficiencymfinally, a third haplotype HL-A2,W18 carrying a defective C2 gene was demonstrated in a part of this pedigree.

Complement C2↗
PubMed1975

The role of complement, immunoglobulin and bacterial antigen in coagulase-negative staphylococcal shunt nephritis.

We describe three patients with arrested hydrocephalus in whom glomerulonephritis developed secondary to Staphylococcus epidermidis bacteremia from an infected ventriculoatrial shunt. Investigation of the immune-mediated renal disease associated with this chronic infection showed that (1) complement depletion during the acute phase of bacteremia and nephritis was predominantly via the classic pathway; (2) rheumatoid factor was associated with bacteremia, fever, proteinuria and low complement levels; (3) early complement components (C1q, C4, C3), immunoglobulin (predominantly immunoglobulin M [IgM], Staph. epidermidis antigen(s) and electron denxe subendothelial deposits were localized within the renal glomerulus; (4) C1q, and IgM derived from patient serums, were the most prominent in vitro immunoreactants to Staph. epidermidis cell walls; and (5) the causative organisms, Staph. epidermidis, shared common antigens with Staph. aureus, and antibody from patient serums cross reacted with extracts from both of these organisms.

Antigens, Bacterial↗
PubMed1975

Studies of the rate of regression of the glomerular lesions in diabetic rats treated with pancreatic islet transplantation.

Diabetes was induced in Lewis rats with streptozotocin. Six to eight months later glomeruli showed mesangial thickening: IgG, IgM and C3 were seen in large quantities in the mesangium by immunofluorescent microscopy. Ten animals then had successful pancreatic transplantation resulting in normal glucose and insulin levels within one to three weeks. Biopsies obtained within the first two weeks following transplantation demonstrated a significant reduction in mesangial thickening and in mesangial staining for IgG, IgM and C3. Three to four weeks after transplantation C3 staining was no longer detected. A gradual reduction in mesangial IgG and IgM localization continued so that by nine weeks following islet transplantation only minimal staining for immunoglobulins was present. Although mesangial thickening was reduced, this abnormality could still be detected in most animals six to nine weeks after transplantation. Three rats showed improvement in glomerular morphology within two weeks despite persistent hyperglycemia. These rats had normal insulin levels at this time. Islet transplantation in inbred diabetic rats effectively returns glucose and insulin levels to normal and results in rapid regression of the light microscopic and immunopathologic glomerular lesions. These studies support the concept of reversible mesangial dysfunction in diabetic rats.

Animals↗
PubMed1975

Deficiency of the second component of complement (C2) with chronic vasculitis.

A patient had complete deficiency of the second component of complement associated with chronic vasculitis and increased susceptibility to infection. We discuss here results of the complement profile, histocompatibility typing, and studies of the functional properties of patient plasma or serum in chemotaxis and opsonization in relation to the disease entity and host susceptibility to infection.

Adult↗
PubMed1975

Unilateral renal disease in the rat. I. Clinical, morphologic, and glomerular mesangial functional features of the experimental model produced by renal perfusion with aminonucleoside.

Unilateral renal perfusion with the aminonucleoside of puromycin (60 mg. per kilogram) was used to produce unilateral renal disease in rats characterized by marked proteinuria, hypoalbuminemia, and hypercholesterolemia. Urine albumin excretion increased from 0.21 plus or minus 0.16 mg. per 24 hours prior to perfusion to 126 plus or minus 30 mg. on the fourteenth day after perfusion. If the perfused kidney was removed after 10 days, urine albumin excretion immediately decreased to normal, whereas marked proteinuria continued after contralateral nephrectomy. Immunofluorescent studies revealed abundant protein reabsorption droplets (beta1C and albumin) in proximal tubules of aminonucleoside-perfused kidneys but not in contralateral kidneys thus indicating that the increased proteinuria was of unilateral origin. Less marked proteinuria was observed following unilateral renal perfusion with lower doses of aminonucleoside. Glomerular mesangial function was studied 10 days after renal perfusion. Renal specimens were obtained 12 hours after intravenous injection of 37.5 mg. per 100 Gm. of body weight of aggregated human IgG and evaluated by immunofluorescent microscopy. Glomerular mesangial staining for human IgG in aminonucleoside-perfused kidneys was markedly increased when compared to contralateral kidneys. In contrast, mesangial staining in kidneys perfused with saline was equal to that of contralateral kidneys and proteinuria following perfusion with saline was not increased. These studies provide further evidence that increased proteinuria following administration of aminonucleoside to rats is the result of a rapid direct on the kidney and that alterations of glomerular mesangial function are related to renal factors rather than changes in systemic milieu.

Albumins↗
PubMed1975

The effect of anticomplementary substances on properdin in normal and C2-deficient sera.

The effect of anticomplementary substances, including zymosan, cobra venom, endotoxin, inulin and immune complexes, on serum properdin concentration and immunoelectrophoretic mobility was studied. In normal serum, zymosan, inulin and immune complexes 'fixed' properdin, while in C2-deficient serum, only zymyosan 'fixed' properdin. Slowly migrating properdin (P) was detected in normal serum following activation by endotoxin and cobra venom but in C2-deficient serum only with cobra venom. Endotoxin did not activate the alternative pathway proteins studied in C2-deficient serum. Fast migrating properdin (P) represented activated properdin and occured as a result of activation of properdin in the Noble agar medium used for electrophoresis provided sufficient cofactors, including Mg2+, were present.

Antigen-Antibody Complex↗