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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 109 records · Page 6Linked to original sources
PubMed1983

Experimental IgA nephropathy in bile duct ligated rats.

Polymeric IgA and polymeric IgA-containing immune complexes are transported from blood to bile through hepatocyte-bound secretory component. In order to investigate interruption of this transport and its effect on the glomerulus, Sprague-Dawley rats underwent bile duct ligation. Renal tissue obtained at the time of sacrifice was stained by immunofluorescent techniques with antibodies to IgG, IgM, and IgA, and secretory component (SC) and C3. A progressive selective increase in the staining intensity of the glomerular mesangium was observed for IgA, C3, and SC in bile duct ligated rats. These changes were paralleled by a rise in serum IgA and C3. These findings are consistent with the view that glomerular deposition of IgA, C3, and SC in bile duct ligated rats may result from impairment of normal handling of polymeric IgA and polymeric IgA-containing immune complexes.

Animals↗
PubMed1983

Absence of Goodpasture's antigen in male patients with familial nephritis.

The presence of Goodpasture's (GP) antigen in the glomerular basement membrane (GBM) of the kidney was evaluated by indirect immunofluorescence in nine patients with familial nephritis from five kindreds. The GP antigen was not detected in seven males but was present in an affected sister and mother, an unaffected brother, and 13 normal controls. The specificity of this finding in affected males is supported by the persistence of other GBM antigens identified by monoclonal antibodies. The lack of GP antigen in affected males and its persistence in related females with the disease suggests a possible X-linked dominant mode of inheritance. We propose that the absence of GP antigen leads to severe disease in the male, whereas its presence in related females is associated with mild disease.

Anti-Glomerular Basement Membrane Disease↗
PubMed1983

Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease.

A monoclonal antibody to a neoantigen of the C9 portion of the membrane attack complex (MAC) of human complement has been developed and characterized. The distribution of this neoantigen was assessed by indirect immunofluorescence microscopy in nephritic and nonnephritic renal diseases. The antibody (Poly C9-MA) reacted on enzyme-linked immunosorbent assay (ELISA) with a determinant in complement-activated serum that was undetectable in normal human serum (NHS). Zymosan particles incubated in NHS had positive immunofluorescent staining with Poly C9-MA; however, binding of Poly C9-MA was not observed with zymosan particles incubated in sera deficient in individual complement components C3, C5, C6, C7, C8, or C9. Reconstitution of C9-deficient sera with purified C9 restored the fluorescence with Poly C9-MA. Poly C9-MA reacted positively by ELISA in a dose-dependent manner with purified MC5b-9 solubilized from membranes of antibody-coated sheep erythrocytes treated with NHS but not with intermediate complement complexes. Poly C9-MA also reacted in a dose-dependent manner on ELISA and in a radioimmunoassay with polymerized C9 (37 degrees C, 64 h) (poly C9) but not with monomeric C9. Increasing amounts of either unlabeled poly C9 or purified MC5b-9 inhibited the 125I-poly C9 RIA in an identical manner. These studies demonstrate that Poly C9-MA recognizes a neoantigen of C9 common to both the MAC and to poly C9. By immunofluorescence, Poly C9-MA reacted minimally with normal kidney tissue in juxtaglomerular loci, the mesangial stalk, and vessel walls. Poly C9-MA stained kidney tissue from patients with glomerulonephritis in a pattern similar to that seen with polyclonal anti-human C3. In tissue from patients with nonnephritic renal disease--diabetes, hypertension, and obstructive uropathy--Poly C9-MA was strongly reactive in the mesangial stalk and juxtaglomerular regions, tubular basement membranes, and vascular walls. Poly C9-MA binding was especially prominent in areas of advanced tissue injury. Poly C9-MA frequently stained loci where C3 was either minimally present or absent. These studies provide strong evidence for complement activation not only in nephritic but also in nonnephritic renal diseases.

Adult↗
PubMed1983

Retardation of fading and enhancement of intensity of immunofluorescence by p-phenylenediamine.

The effects of p-phenylenediamine (PD) on the extinction and intensity of fluorescence and on antigen binding in immunofluorescence microscopy was investigated. Visual and photometric comparison of tissue sections reacted sequentially with polyclonal or monoclonal antisera and appropriate fluorochromes and mounted with and without PD indicated that PD both prolonged and intensified fluorescence without evident effect on antibody binding.

Fluorescent Antibody Technique↗
PubMed1983

Polyantigenic expansion of basement membrane constituents in diabetic nephropathy.

The immunohistopathology of the intrinsic basement membrane-associated antigens were examined in diabetic nephropathy. In early and moderate stages of disease there was polyantigenic expansion of all the intrinsic components of mesangium, glomerular basement membrane (GBM), and tubular basement membrane (TBM) assessed by polyclonal antisera to collagen types IV and V, laminin, and by monoclonal antibodies to type IV collagen and fibronectin and to four other intrinsic components of normal renal extracellular matrices (MBM10, 11, 12, and 15). In the mesangium the first intrinsic antigens to increase were fibronectin and type V collagen. In late stages of disease, there was a diminution in the mesangium of all of these antigens with the exception of type V collagen, which persisted. Additionally, antigens appeared in the mesangium, recognized by MBM11 and MBM15, which are normally present in fetal but not adult mesangial regions. Similarly, in the GBM in late stages of disease, there was a decrease in all of the antigens, except for a persistence of the antigen recognized by MBM15. However, in TBM all of the antigens assessed increased in early, moderate, and severe disease. These studies document the complexity of polyantigenic alterations in the development of diabetic nephropathy.

Animals↗
PubMed1983

Glucosylated and normal human of rat albumin do not bind to renal basement membranes of diabetic and control rats.

Hyperglucosylated and normal human and rat albumin were injected intravenously into control and streptozotocin-induced diabetic rats. Binding of injected human albumin to renal basement membranes was not observed by immunofluorescence microscopy in the diabetic or control rats irrespective of the form of injected albumin. However, human albumin was found as tubular droplets in both the control and diabetic rats injected with either form of albumin. Spontaneous binding of endogenous rat albumin was observed in a linear pattern on diabetic rat glomerular basement membranes (GBM), but not in the GBM of control rats. No appreciable differences in the intensity of staining for rat albumin was observed in diabetic rats injected with either glucosylated or normal rat albumin. Similarly, no binding of rat albumin to the GBM was observed in control rats irrespective of the type of albumin injected. These studies demonstrate that binding of albumin to renal basement membranes is not dependent on glucosylation.

Animals↗
PubMed1983

Renal localization of heparan sulfate proteoglycan by immunohistochemistry.

Glomerular localization of heparan sulfate proteoglycan (HS-proteoglycan) has been studied immunohistochemically with a highly purified antiserum to bovine aorta HS-proteoglycan core protein. The specificity of the antiserum was enhanced by consecutive fibronectin and chondroitin sulfate-dermatan sulfate proteoglycan (CS-DS proteoglycan) affinity chromatography. The affinity-purified HS-proteoglycan antibody lacked cross-reactivity by enzyme-linked immunosorbent assays (ELISA) with CS-DS proteoglycan, fibronectin, laminin, and Type IV collagen. Reactivity of the antiserum with HS-proteoglycan antigen by ELISA was inhibited by HS core protein derived from CsCl density gradient centrifugation after heparinase treatment of the HS-proteoglycan. Immunofluorescent reactivity of the HS-proteoglycan antiserum was observed with bovine glomerular basement membrane, renal interstitium, Bowman's capsule, renal arterioles, and bovine aorta. No staining was seen with rat, mouse, or human glomeruli.

Animals↗
PubMed1983

Prevention of the generalized Shwartzman reaction in pregnant rats by prostacyclin infusion.

The effects of prostacyclin infusion on endotoxin-induced generalized Shwartzman reaction were studied in pregnant rats. Four hours after administration of Escherichia coli endotoxin (0.4 mg) to pregnant rats on the 20th day of gestation, fibrin and platelet thrombi were observed in 72% of the animals. These findings were associated with a decrease in renal blood flow and glomerular filtration rate from 7.0 to 0.7 and 0.8 +/- 0.1 to 2.6 +/- 0.4 and 0.2 +/- 0.8 ml/minute, respectively (p less than 0.0001 and less than 0.05) and a decrease in platelet count (p less than 0.05). The infusion of prostacyclin, at a mean dose of 57 ng/kg/minute prior to and after administration of endotoxin strikingly inhibited the development of fibrin and platelet thrombi in glomerular capillaries (p less than 0.001). Despite hemodynamic changes which were similar to those in control animals, renal blood flow and glomerular filtration rate decreased from 7.2 +/- 0.2 and 0.9 to 2.9 +/- 0.03 and 0.3 +/- 0.1 ml/minute, respectively (p less than 0.001 and less than 0.025). In addition, the mean blood pressure decreased from 118 +/- 3.8 to 86 +/- 3.7 mm Hg (p less than 0.025), whereas the platelet count remained normal. We conclude that prostacyclin infusion prior to endotoxin administration significantly inhibits endotoxin-induced generalized Shwartzman reaction in pregnant rats.

Animals↗
PubMed1983

The effect of charge on the renal distribution of ferritin.

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.

Animals↗
PubMed1982

Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections.

The interstitial mononuclear cell populations of 22 renal grafts with interstitial rejection (IR), 6 grafts with interstitial nephritis without rejection (IN), and 5 kidneys without infiltration (3 donor kidneys, 2 grafts) were identified and quantitated by monoclonal antibodies recognizing T cells (TA-1, OKT3), helper inducer cells (OKT4), cytotoxic/suppressor cells (OKT8), B cells (BA-1), and monocytes and null cells (OKM1). Double-layer fluorochrome enhancement using F(ab')(2) reagents and nuclear counter staining with ethidium bromide enabled quantitation of the number of positive mononuclear cells, interstitial cells, and total cells on each of 30-55 microscopic fields per tissue section. T cells were the most abundant infiltrating cell in tissues with IR (35 +/- 9.8 percent), significantly higher than that seen in IN (21 +/- 16 percent) or in kidneys without infiltration (5.0 +/- 3.9 percent). The percentage of T cells identified by TA-1 or OKT3 was approximately equivalent to the summation of OKT4 plus OKT8. Although no differences were observed in the percentage of OKT4 cells, the percentage of OKT8 was significantly higher in IR (26 +/- 7.7 percent, P {less than} 10(-4)) than in IN (9.3 +/- 6.2 percent) or in kidneys with normal interstitium (3.0 +/- 2.4 percent). The ratio of OKT8/OKT4-positive T cells in 22 graft tissues with IR (3.2 +/- 1.4) was greater (P {less than} 0.0007) than 6 graft tissues with IN without rejection (0.82 +/- 0.39) and the 5 kidney tissues without interstitial infiltration (0.75 +/- 0.25). There was no significant difference between the groups in the relatively low percentage of interstitial cells identified as B cells reacting with BA-1 or containing S(IgD,M). The percentage of interstitial cells recognized by OKM1 was similar in rejection and interstitial nephritis, with both being greater than controls (P {less than} 0.02). The relative numbers of blood mononuclear cells identified by the monoclonal antibodies was generally not predictive of the proportions present in kidney tissue, although OKT4-positive blood cells were less numerous and OKMI+ blood cells were more numerous than in controls (P {less than} 0.002). Quantitative analysis of identifiable interstitial cells in graft rejection reveals that most infiltrating cells are T cells, the greater proportion of which are recognized by OKT8. OKT8-positive cells may play an important role in mediating renal graft rejection.

Adolescent↗
PubMed1982

Progressive encephalopathy in children with chronic renal insufficiency in infancy.

A retrospective analysis of children with renal failure during the first year of life revealed that 20 of 23 patients developed profound neurologic abnormalities. The encephalopathy was characterized by developmental delay, microcephaly, hypotonia, seizures, dyskinesia, and EEG abnormalities. No patient had been dialyzed, and four had not received aluminum salts prior to the development of neurologic symptoms. Inadequate statural growth and poor nutrition were present in all patients. It is probable that infants with chronic renal insufficiency are more susceptible to the development of this syndrome than are older children or adults because of the significant growth and maturation of the brain that occurs during the first years of life.

Body Height↗
PubMed1982

Preservation of mesangium and immunohistochemically defined antigens in glomerular basement membrane isolated by detergent extraction.

To define the characteristics of isolated glomerular basement membrane (GBM), immunohistochemical and morphometric analyses have been carried out on rat and human tissues. Site-specific arrays of antigens were identified in detergent-isolated GBM in a distribution similar to that observed in intact kidney. In the human, fibronectin, procollagen IV, and collagen V were observed along the internal aspect of GBM continuous with antigenic sites in the mesangium. Another array of antigens was identified in the GBM but not within the mesangium--Goodpasture's antigen, bovine lens capsule type IV collagen, and amyloid P component. In addition, sites reactive with rabbit antiserum to laminin were present on both sides of the lamina densa as well as within the mesangial region. Actomyosin, a presumed mesangial cell antigen persisted in the mesangium of isolated GBM. Mesangial matrix was identified in detergent-isolated GBM in an amount equivalent to that present in intact glomeruli. Sonicated GBM contained the same antigens but it was not possible to quantitate the amount of mesangial material by immunofluorescence or morphometric analysis. The thickness of the lamina densa was greater in sonicated and detergent-treated rat GBM preparations than in native rat kidney. These studies demonstrated that isolated GBM is heterogeneous with respect to its antigenic constituents and in addition contains mesangial matrix, which is morphologically and immunohistochemically distinct from peripheral GBM.

Actomyosin↗