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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 145 records · Page 8Linked to original sources

Localization of platelet antigens in human kidney disease.

The localization of a platelet antigen or antigens kidneys from 106 patients with renal disease was evaluated with immunofluorescent microscopy by using a rabbit antibody to human platelets. The antiplatelet IgG fixed to the surface membrane of platelets did not react with erythrocytes, leukocytes, plasma, normal kidney, or a variety of normal tissue targets. Significant glomerular and vascular deposition of platelet antigen (or antigens) was observed along the endothelium or as vascular plugs in kidney tissue from patients with hemolytic uremic syndrome, membranoproliferative glomerulonephritis (types I and II), diabetic nephropathy, hypertensive renal disease, scleroderma, and other diseases. Dual-label immunofluorescent studies revealed that platelet antigen (or antigens) and fibrinogen/fibrin-related antigen (FRA) were usually, though not always, present in similar loci. Platelet antigens were not observed at sites of intense FRA deposition: in the mesangium in anaphylactoid purpura and in glomerular crescents in Goodpasture's syndrome. Platelet antigen was detected in the peritubular capillaries of most patients with diabetic nephropathy.

Antigens↗

Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus.

To further characterize the IgA deposits found in glomeruli of patients with IgA nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus, renal biopsies from patients with these disorders were stained by immunofluorescence with monoclonal anti-IgA subclass reagents, anti-light chain reagents and anti-J chain. The mesangium and peripheral capillary were brightly stained for IgA1 and were negative for IgA2. IgA1 and, to a lesser extent, IgA2 were contained in tubular casts. Both kappa and lambda light chains were found in all deposits. The intensity of J chain staining correlated with the intensity of IgM and not IgA staining. Biopsies brightly stained for IgA but negative for IgM were negative for J chain. These results indicate that glomerular IgA deposits in these disorders consist predominantly of monomers of IgA1.

Humans↗

Uptake of aggregated immunoglobulin by the mouse kidney. I. Effect of endotoxin.

Endotoxin (ET) pretreatment of mice resulted in increased liver and spleen uptake and decreased circulating levels of aggregated IgC (AggIgG) compared to control animals. ET had no effect upon the uptake of AggIgG by lung or whole kidney cortex. However, immunofluorescent microscopy revealed increased localization of AggIgG in the mesangium of ET mice at 1 but not at 2 or 16 h after administration of AggIgG. These studies show that mesangial macromolecular uptake is not solely dependent upon blood levels, but appears to be influenced by unknown and probably complex variables.

Animals↗

Uptake of aggregated immunoglobulin by the mouse kidney. II. Effect of hydrocortisone.

The uptake of radiolabelled (125I) aggregated human IgG (AggIgG) by the renal cortex, liver, spleen and lung was evaluated quantitatively in mice treated with hydrocortisone (HC) (25 mg) 72 h previously. AggIgG was administered in a dose of 1.5 or 3.5 mg/g body wt i.v.; tissue and blood were obtained at 1, 4 and 24 h. Renal cortical and mesangial uptake of AggIgG was significantly increased in HC animals. A rise in blood level was also observed in association with decreased splenic uptake, normal or slightly increased hepatic uptake and unchanged lung uptake. A significant increase in the kidney:lung and kidney:spleen ratios of AggIgG was induced by hydrocortisone, suggesting a relatively greater rate of loss from the spleen and liver than the renal cortex. The increased mesangial uptake may be a consequence of higher blood levels of AggIgG, as well as a direct effect of HC on the mesangium.

Animals↗

The immunohistology of glomerular antigens. V. The collagenous antigens of the glomerulus.

Distinct antigenic loci are present within the human glomerulus as demonstrated by high resolution epifluorescent and phase-contrast microscopic techniques using affinity-purified antibody to characterized collagens. Type IV mouse tumor procollagen and type V collagen are present within the mesangium and along the endothelial aspect of the glomerular basement membrane, demonstrating antigenic continuity between these two glomerular zones. In contrast, antiserum to type IV collagen from bovine lens capsule reacts with the full thickness of the glomerular basement membrane, as well as in the tubular basement membrane and Bowman's capsule. Types I procollagen and collagen are found within the epithelium; and types III collagen and procollagen are not detected within the glomerulus. The functional role of the multiple distinct "basement membrane" collagens in the glomerular capillary wall is unknown. A complex structure is suggested, especially in the mesangial-subendothelial continuity, and in the differential localization of two forms of type IV collagen within the glomerular basement membrane.

Animals↗

L-asparaginase-induced hypocomplementemia in acute lymphocytic leukemia (ALL) of childhood.

Serum complement studies were carried out in five children with acute lymphocytic leukemia. During therapy with L-asparaginase, prednisone and vincristine, hypocomplementemia developed in all patients, and disappeared within 2 weeks after the discontinuation of L-asparaginase. Complement breakdown products were not present in plasma. The changes of serum complement levels paralleled those of plasma fibrinogen. These findings suggest that the hypocomplementemia observed in these patients may be related to impaired protein synthesis induced by L-asparaginase.

Adolescent↗

Immunofluorescence studies of dense deposit disease. The presence of railroad tracks and mesangial rings.

Immunopathologic analysis was carried out on renal tissue from patients with membranoproliferative glomerulonephritis, nine with type I and nine with type II (dense deposit disease). A specific finding in all patients with type II, but not type I, was the presence of C3 along the margin but not within the central portion of dense deposit material in the glomerular basement membrane giving a double linear appearance (railroad tracks); C3 was also present within the mesangium, outlining numerous circular structures (mesangial rings). By phase contrast, electron microscopy, and dual label fluorescence studies, the railroad tracks and mesangial rings were shown to outline dense deposit material. Mesangial rings contained properdin (four of nine patients); railroad tracks contained properdin (five of nine patients) and C4 (four of nine patients); no other complement components or immunoglobulins were present. Studies using rhodamine-conjugated rabbit antibody to human glomerular basement membrane demonstrated no reactivity with the dense deposit material itself. In type I and to a lesser extent in type II, granular deposits of C3, C4, properdin, IgM, and IgG were present along the glomerular basement membrane, suggesting that immune complexes play a role in both diseases. Dense deposit transformation of the glomerular basement membrane may be a consequence of a highly specific injury.

Autoantibodies↗

Spatial orientation and distribution of antigens within human glomerular basement membrane.

Antibodies to GBM have a linear staining pattern along the GBM by immunofluorescence. In this study, we have examined the distribution of human GBM antigens using Goodpasture antibody and heterologous rabbit anti-human GBM antibody. Goodpasture sera and Goodpasture antibody eluted from diseased kidneys reacted as a single linear component within the GBM. Rabbit anti-human GBM was shown to react along distinctly separate zones of the inner and outer aspects of the GBM; the central portion of the GBM seemed to be nonreactive with this antibody. In comparison, Goodpasture antibodies reacted along the inner zone of the GBM but at a locus external to that reacting with heterologous rabbit anti-GBM antibody. These observations of linear binding of antibody to different sites along the GBM suggest a spatial organization of antigen not previously observed.

Anti-Glomerular Basement Membrane Disease↗

B lymphocyte determinants in immunoglobulin A nephropathy.

Because of our prior demonstration of a strong association betwen a specific B lymphocyte determinant and the occurrence of chronic membranoproliferative glomerulonephritis and the demonstration by others of the frequent concurrence of an IgA deposit disease, anaphylactoid purpura nephritis,with HLA-BW35, we conducted an investigation of the association among Minnesota Caucasians of the HLA markers BW35, DW1 and B lymphocyte determinants identified by three alloantisera with IgA nephropathy and the syndrome of recurrent macroscopic hematuria. The highly significant association between HLA-BW35, DW1, and B cell antigens identified by alloantisera L, B, and F, present in 50 normal Minnesota Caucasians, was not observed in 18 Minnesota patients with IgA nephropathy. The frequency of HLA-DW1 was the same among controls and patients, whereas the relative risk of developing IgA nephropathy was demonstrated to be increased 4- to 5-fold in the presence of the B cell antigens identified by alloantisera L and B. These sera appear to identify determinants on B lymphocytes associated with the disease state and possibly not intimately related to the HLA-D region. These findings emphasize the possible informativeness of defining B cell alloantisera on disease panels.

Antilymphocyte Serum↗

Collagen synthesis by human glomerular cells in culture.

Collagen synthesis was studied in three subcultured human glomerular cell types, by radiolabeled incorporation of [14C]proline and [3H]lysine. The epithelioid circular glomerular cells secrete a collagen with a single size of chain (possibly type IV) with a high ratio of hydroxyproline to proline, hydroxylysine to lysine, and 11--17% of hydroxyproline as the 3-isomer. The smooth muscle-like rhomboid glomerular cells secrete collagen with a chain pattern suggesting types III and I collagen, distinct from that found in the media of fibroblasts. Small ovoid glomerular cells are morphologically and biochemically intermediate between circular glomerular cells and rhomboid glomerular cells, and may represent an in vitro modification of either circular glomerular cells or rhomboid glomerular cells.

Basement Membrane↗

Activation of complement by cell surface components of Staphylococcus aureus.

The abilities of intact Staphylococcus aureus H, crude cell walls (CCW), purified cell walls (PCW, peptidoglycan [PG] and covalently linked teichoic acid), peptidoglycan, and cell membranes (CM) to activate the complement system in normal human serum, C2-deficient serum, and immunoglobulin-deficient serum were compared. On a weight basis, PCW was the most active fraction; intact organisms and CCW were about equally effective; and PG was least active in causing complement consumption in normal serum. CM also activated complement but did not give a clear dose-response relationship in the concentrations used. Kinetic studies revealed that C3-C9 consumption occurred at a significantly slower rate in C2-deficient serum, indicating that intact organisms, PCW, and PG may activate the complement system via the classical and alternative pathways in normal serum. C3-C9 consumption was also slower in immunoglobulin-deficient serum than in normal serum, implying that immunoglobulins play a role in attaining maximum rates of complement activation. In all sera studied, PG was less active in complement activation than PCW. These results indicate that a number of cell surface components of S. aureus can play a role in complement activation by this organism and that the presence of teichoic acid has a significant enhancing effect in this regard.

Cell Membrane↗