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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 127 records · Page 7Linked to original sources

35S-glycosaminoglycan and 35S-glycopeptide metabolism by diabetic glomeruli and aorta.

35S-glycosaminoglycan metabolism by glomeruli isolated from streptozotocin-diabetic and control rats was studied in vivo and in vitro. Total 35S-glycosaminoglycan synthesis and retention in the matrix by diabetic glomeruli was reduced while degradation was increased. 35S-glycosaminoglycan content of isolated GBM was similarly decreased. Whereas 35S-glycosaminoglycan content of glomeruli and GBM was decreased after in vitro incubation with 35SO4, a larger proportion of total 35S-glycosaminoglycans was found in the incubation medium from diabetic glomeruli. Both control and diabetic glomeruli synthesize 35S-labeled glycopeptides, the quantity from diabetic glomeruli being reduced. Aorta from 35SO4-injected diabetic rats also synthesized reduced quantities of 35S-glycosaminoglycans. There were no preferential metabolic alterations of species of 35S-glycosaminoglycans by diabetic glomeruli or aortas. These studies suggest that synthesis of 35S-glycosaminoglycans and 35S-glycopeptides by diabetic glomeruli are altered by disturbances of both synthetic as well as degradative pathways. An alteration of 35S-glycosaminoglycans interaction with matrix components in diabetes is postulated.

Animals↗

The human FcR. III. Effects of pronase on soluble immune complex binding by polymorphonuclear leucocytes, monocytes and pulmonary macrophages.

The effect of Pronase incubation on the Fc receptors of human polymorphonuclear leucocytes (PMN), monocytes and pulmonary alveolar macrophages was evaluated by Scatchard analysis of the binding of soluble immune complexes at equilibrium. All three cell types, when preincubated with Pronase, demonstrated a significant increase in Fc receptor affinity. Maximum binding (which measures the number of Fc receptors) on polymorphonuclear leucocytes was reduced 45%-50% but was unchanged on monocytes and pulmonary macrophages. The changes in Fc receptor affinity and maximum binding of the PMN were reversible in short-term culture, an effect which was prevented by cycloheximide. These studies indicate that the affinity of the Fc receptor of human phagocytic cells may change significantly independent of changes in receptor number and that this effect can be caused by extracellular proteases. In addition, the human polymorphonuclear leucocyte demonstrates a subpopulation of Fc receptors which is decreased by Pronase and which recovers, in vitro, by a process requiring protein synthesis.

Antigen-Antibody Complex↗

Systemic lupus erythematosus in the first two decades of life.

Seventy patients with systemic lupus erythematosus (SLE) in the first two decades of life have been followed from 1958 to 1981. The patients were treated with corticosteroids alone (17 patients) or corticosteroids and immunosuppressives (53 patients). Twenty-one patients (30%) had evidence of CNS lupus. Eighty-seven percent of patients had evidence of renal involvement, and 34% of these patients had diffuse proliferative lupus nephritis (DPLN). A high frequency of pathologic transition was found to occur. Analysis of 20 pregnancies in 12 women with SLE reveals that patients with active SLE and/or renal disease are at a high risk for complications of pregnancy in contrast to patients in remission. The occurrence of infection, aseptic necrosis and cataracts is shown to be related to SLE itself and to its treatment. By life table analysis overall survival was 90% at 1 yr, 85% at 10 yr. and 77% at 15 yr. Survival of patients who entered the study before age 16 and of patients with CNS lupus could not be distinguished from that of the total group. Patients who entered the study from 1974-1981 had 5-yr survival similar to that of the total group. Survival of 21 patients with DPLN did not deviate from that of the entire group until 14 yr after study entry (7 yr if dialysis and transplantation are considered as deaths). In conclusion, the prognosis of SLE and especially of DPLN in the younger patient appears to be better than indicated by prior reports. Thus, analysis of outcome in this disease may require a long duration of follow-up.

Adolescent↗

Binding of soluble immune complexes by human monocytes and pulmonary macrophages: effects of cigarette smoking.

The Fc receptor of human monocytes and pulmonary macrophages has been evaluated quantitatively by binding of radiolabeled soluble IC. On both cell types, binding was mediated by saturable surface receptors specifically inhibited by aggregated human IgG1 and IgG3. The affinity of the Fc receptor was similar on monocytes and pulmonary macrophages from nonsmokers, but macrophages demonstrated four to 13 times more surface receptors than circulating monocytes. No difference in Fc receptor binding of monocytes was observed between cigarette smokers and nonsmokers. However, pulmonary macrophages from smokers demonstrated a significantly lower Fc receptor affinity than did those of nonsmokers, although the number of Fc receptors was the same.

Antigen-Antibody Complex↗

Glycosaminoglycan synthesis by glomeruli in vivo and in vitro.

The distribution of glycosaminoglycans in disrupted glomerular fractions was studied using 35SO4-labeling in vivo and in vitro. The majority of 35S of isolated glomerular basement membrane was found in heparan sulfate after in vivo and in vitro pulses, although the absolute proportion and the degrees of N-sulfation and N-acetylation varied with the conditions of exposure. Varying amounts of chondroitin sulfate and dermatan sulfate were found in the glomerular basement membrane fraction and larger proportions of both of these glycosaminoglycans as well as of heparan sulfate were found in various glomerular fractions. Glomerular glycosaminoglycans distribution studies must take into account the experimental conditions. Basement membrane-like components of the glomerulus such as the mesangial matrix may have varying glycosaminoglycan composition which may be found in association with glomerular basement membrane fractions.

Animals↗

Influence of age and sex on serum complement components in children.

Concentrations of eight complement components were determined on sera from 419 healthy children (198 boys and 221 girls) aged from 1 to 19 years. A significant correlation between concentration and age for all complement components (C1q, C1s, C4, C3, C5, factor B, properdin, and C1 inhibitor) was observed for girls; in the male population, a significant correlation was present only for C1q, C4, C3, C5, and properdin. The presence of a significant relationship to age suggests that this variable must be considered in establishing normal values of serum complement for children.

Adolescent↗

Isolation of anionic sialoproteins from the rat glomerulus.

The epithelial glomerular polyanion (GPA) designates an array of sialic acid-containing sites along the surface of the glomerular epithelium which react with cationic dyes or probes. In this work, sequential rat glomerular isolation, ultrasonic disruption, trypsin digestion, ion-exchange chromatography, and preparative polyacrylamide gel electrophoresis have been used to isolate anionic sialoglycoproteins from the glomerular epithelium. Because colloidal iron (CI) reactivity has been used to define the GPA histologically, we used a modification of the CI reaction to monitor and direct the isolation procedure. Three major fractions have been recognized and isolated in homogeneity. Antibodies to two of the fractions have been raised by immunization in rabbits. Indirect immunofluorescent and peroxidase-antibody techniques have localized both antigens to the glomerular visceral epithelium of normal rat kidney. This identification and definition of components of the GPA is valuable in delineating a role for GPA in glomerular function.

Animals↗

Increased concentration of albumin in kidney basement membranes in diabetes mellitus.

The concentration of albumin was measured by a double-antibody radioimmunoassay in the glomerular basement membrane (GBM) and tubular basement membrane (TBM) of patients with diabetic nephropathy, other kidney diseases, and normal kidneys. The TBM from diabetics contained significantly more albumin (m +/ SD; 2.75 +/- 0.34 microgram/mg) than the TBM from other diseases (1.00 +/- 0.24 microgram/mg) or normals (1.21 +/- 0.26 microgram/mg) (P less than 0.0001). Similarly, diabetic GBM contained more albumin (2.25 +/- 0.59 microgram/mg) than other diseases (1.22 +/- 0.55) or normals (1.31 +/- 0.36 microgram/mg) (P less than 0.01-0.001). No differences were observed between the normal and other disease groups. Although there were no differences in hydroxyproline content, there was a highly significant correlation between the concentration of hydroxyproline and albumin in the diabetic TBM (r = 0.82), diabetic GBM (r = 0.70), and normal TBM (r = 0.79). Elution studies with different buffers on frozen sections of diabetic kidneys suggest that the albumin is relatively firmly bound. Although albumin is present in extracellular membranes of normal and diseased human kidneys, the concentration is higher in diabetes mellitus.

Adolescent↗

Albumin deposition in dermal capillary basement membrane in insulin-dependent diabetes mellitus. A preliminary report.

Skin specimens obtained from 24 insulin-dependent diabetics (IDD) and 35 controls were examined by immunofluorescence (IF) microscopy. An increased percentage (greater than 8%) of dermal vessel basement membranes (BM) showing circumferential fluorescence for albumin was observed in 18 of 24 IDD (duration of diabetes 1.5-33 yr) and 1 of 35 controls. Dual label studies using fluorescein-conjugated anti-human albumin and rhodamine-conjugated anti-human BM confirmed that localization of albumin was within the BM. These studies suggest that increased albumin localization in extracellular BM may be widespread in diabetes.

Adolescent↗

Distribution of glomerular basement membrane antigens in diseased human kidneys.

We have previously shown, using high resolution epifluorescence microscopy, that heterologous rabbit antihuman glomerular basement membrane (GBM) antibody (RAHGBM) stains the GBM of normal human kidney in a bilaminar distribution along the endothelial and epithelial aspects of the GBM. In contrast, Goodpasture (GP) antibody stains a single linear component along the inner aspect of the GBM. In the present study, alterations in the staining reactivity of these components appear consistently to correlate with the known morphologic changes in various glomerulopathies. In idiopathic nephrotic syndrome, no changes from normal were observed. In membranous glomerulopathy, the inner RAHGBM antigen was preserved, but the outer antigen showed an irregular beaded alteration adjacent to membranous GBM immune deposits. In diabetic glomerulopathy, striking increase in the inner RAHGBM component was evident with markedly increased separation from the outer RAHGBM line. In membranoproliferative glomerulonephritis (MPGN), loss of the inner component but preservation of the outer RAHGBM line was evident; however, in type I MPGN, GP antigen was preserved as a single linear component, but in type II MPGN, there was splitting of GP antigen by GBM-dense deposit material into a double linear array along the endothelial and epithelial aspects of the GBM. These observations serve to substantiate our earlier findings that antigenic and nonantigenic components of the GBM are partitioned in the glomerular capillary wall; their selective characteristic alteration in various glomerulopathies additionally supports this view.

Antigens↗

Soluble immune complexes binding to human monocytes and polymorphonuclear leucocytes.

Soluble human serum albumin anti-albumin immune complexes (IC) have been shown to bind to freshly isolated human peripheral blood monocytes and polymorphonuclear leucocytes (PMN) in vitro. Binding sites on both cell types were saturable and specifically inhibited by heat aggregated IgG1 and IgG3 subclasses. PMN contained a greater number of binding sites than monocytes although the affinity was similar for both cell types. The enhanced binding of IC by both cell types observed after incubation at low pH (pH 6.0) was a consequence of increased affinity of the PMN binding site and an increase in the number of sites in monocytes. Binding of IC by both cell types was inhibited by normal human serum. Enhanced IC binding associated with enhanced affinity and number of sites was observed in PMN and monocytes preincubated in suspension with trypsin. However, monocytes exposed to trypsin while adherent to microexudate coated flasks demonstrated a marked increase in affinity without any change in the number of sites.

Animals↗

Pregnancy and systemic lupus erythematosus.

Eleven patients with 18 pregnancies occurring during the course of systemic lupus erythematosus (SLE) were reviewed. Ten had long-standing lupus glomerulonephritis and a single patient developed glomerulonephritis during pregnancy. Patients were divided into those without (Group A) and those with (Group B) clinical evidence of renal disease or active SLE at conception. In Group A there were 10 pregnancies in five patients; all pregnancies were uncomplicated, except for mild superimposed pre-eclampsia in two, and all resulted in term delivery. Eight pregnancies in six patients occurred in Group B; four pregnancies were complicated by severe (2) or mild (1) superimposed pre-eclampsia and the onset of glomerulonephritis (1), resulting in three premature deliveries and a spontaneous abortion. The remaining four pregnancies were uncomplicated but resulted in one term delivery, one elective abortion, and two spontaneous abortions. None of the patients developed either renal failure or a rapidly progressive course following pregnancy.

Adult↗