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Biomedical subjects

A F Michael

Publications and source records attributed to A F Michael.

At least 163 records · Page 9Linked to original sources
PubMed1978

Dichotomy between opsonization and serum complement activation by encapsulated staphylococci.

Previous studies have demonstrated that encapsulated Staphylococcus aureus strains are not effectively opsonized by the serum complement system. Encapsulated staphylococci thereby "resist phagocytosis." To test whether this phenomenon might be explained by an inability of encapsulated strains to activate complement, the relationship between staphylococcal opsonization and serum complement activation was studied. Although encapsulation was found to interfere with opsonization by pooled human serum (human polymorphonuclear leukocytes phagocytized significantly fewer encapsulated bacteria than unencapsulated bacteria after incubation in this opsonic source), encapsulated (S. aureus M and Smith diffuse) and unencapsulated (S. aureus M variant and Smith compact) strains had similar capacities for complement activation as measured by C3-C9 consumption. When C2-deficient and immunoglobulin-deficient sera were studied, again C3-C9 consumption was not influenced by the presence or absence of a capsule. In addition, C3 was detected on the surface of both S. aureus M and M variant strains after incubation in pooled serum and staining with fluorescein-conjugated anti-C3 antibody. Thus, encapsulated staphylococci are not effectively opsonized even though complement is activated and C3 is present on the bacterial surface. The exact mechanism by which the capsule interferes with opsonization is still not known; however, inhibition of complement activation appears not to be the explanation of this phenomenon.

Antibodies↗
PubMed1978

The immunohistopathology of glomerular antigens. II. The glomerular basement membrane, actomyosin, and fibroblast surface antigens in normal, diseased, and transplanted human kidneys.

Immunofluorescent studies have demonstrated that actomyosin (AMY) is present in the mesangium in a restrictive pattern, whereas fibroblast surface antigen (FSA) has a more extensive mesangial distribution. Antibody to glomerular basement membrane (GBM) is localized to the GBM. One hundred ninety-six tissue samples, including 17 from normal subjects, 94 from patients with primary renal diseases, and 85 from transplanted kidneys, were examined for changes in distribution of AMY, FSA, and GBM antigens. The distribution of AMY and FSA in the mesangium is markedly increased in width in patients with diabetic nephropathy, and the GBM is thickened. AMY and FSA are mildly increased in patients with glomerulonephritis and GBM is normal. Patients with membranoproliferative glomerulonephritis (MPGN) show a loss of all glomerular antigens. Increased mesangial AMY was found in 12 of 37 transplanted kidneys in diabetic patients vs 4 of 33 nondiabetics 0 to 4 years after transplantation (P < 0.025). This difference is more notable at 2 to 4 years, with 5 of 9 diabetics showing increased AMY vs 0 of 6 nondiabetic patients (P < 0.0005). In MPGN, 5 of 8 tissues showed decreased mesangial AMY vs 3 of 36 diabetic patients (P < 0.0005) and 1 of 32 patients with other glomerulopathies (P < 0.0005). GBM thickening is not associated with specific pretransplant diseases. In transplanted kidneys, the pattern of FSA is dissociated from that of AMY: over half of all patients have increased FSA, even when AMY is normal. Whether this unique finding in transplanted kidneys reflects an increase in the synthesis of FSA by mesangial cells or the failure to clear this (circulating) antigen from the mesangial matrix is unknown.

Actomyosin↗
PubMed1978

Immunofluorescence studies of skeletal muscle extracellular membranes in diabetes mellitus.

Skeletal muscle from 34 insulin-dependent diabetic patients and 20 age-matched controls was examined by immunofluorescent microscopy. Significantly increased staining of capillary and muscle basement membranes of diabetics was seen for IgG, albumin, and fibrin. The immunofluorescent pattern was identical with that observed using heterologous antibasement membrane antiserum, indicating that these proteins were present within these basement membranes. No differences were detected between males and females or between kidney-transplanted and nontransplanted diabetics. No correlation was noted between intensity of staining and duration of diabetes. The presence of certain serum proteins within vascular and nonvascular basement membranes in diabetics is not restricted to the kidney and may reflect widespread alterations in extracellular membranes that permit entrapment of these proteins.

Albumins↗
PubMed1978

Renal cell turnover studied by Y chromosome (Y body) staining of the transplanted human kidney.

To address questions about turnover between human renal cell populations and extrarenal cells, we studied kidneys that had been transplanted between sexes. By staining frozen sections with acranil and enumerating Y bodies, we could distinguish between male and female tubular and glomerular cells in control nontransplant kidneys. We studied 12 kidneys that had been transplanted from females to males, including seven which had mesangial cell hyperplasia in the transplant. There were virtually no Y body-positive nuclei in the glomeruli or tubules of the 12 kidneys. Thus there was no evidence for an extrarenal cell contribution to either normal or proliferative mesangial cells or to other renal cells. Two of these 12 kidneys had cellular glomerular crescents. Y body-postive extrarenal cells were present in the crescents. Interstitial infiltrates in female-to-male transplants were also Y body-positive.

Cell Division↗
PubMed1978

Focal glomerular sclerosis and sarcoidosis.

Idiopathic nephrotic syndrome occurred in a patient with sarcoidosis. Typical features of focal segmental glomerulosclerosis were present on kidney biopsy. A unique finding was the occurrence of IgA in blood vessels of the skin and lymph node. Whereas the sarcoid hilar adenopathy responded to steroid therapy, the nephrotic syndrome was resistant to steroids and immunosuppression. Evaluation of humoral and cellular immune responsiveness showed no abnormalities except cutaneous anergy. Glomerulonephritis is uncommon in sarcoidosis, and a brief outline of this association is included. This patient is of importance in view of the unexplained relationship between idiopathic nephrotic syndrome and T lymphocyte abnormalities.

Adult↗
PubMed1978

C3b receptors on human glomeruli in vitro. Loss in culture.

C3b receptors, easily demonstrated on isolated human infant glomeruli, are lost as cells grow in culture. This suggests that epithelial cells are dedifferentiated or that the C3b receptor is not intrinsic to the epithelial cell.

Cells, Cultured↗
PubMed1978

Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse.

NZB X NZW F1 mice initiated on calorie restriction at weaning or at 4 to 5 months of age or initiated on moderate protein restriction at weaning, were afforded significant protection from the development of immune nephritis. Whereas animals on normal calorie intake demonstrated deposition of immune reactants in glomerular basement membrane-oriented pattern, those on either protein or calorie restriction exhibited mesangial confinement of immunoglobulins and complement. Associated with these divergent patterns of immune deposition, mice on normal calorie intake evidence extensive cellular proliferation and glomerular sclerosis while dietary restricted mice demonstrated virtually no hyalinization and only mild cellular proliferation. Autoantibody formation of calorie-restricted animals was significantly decreased compared to mice fed a normal diet. Thus, moderate dietary restriction may serve as either a prophylactic or effective therapeutic approach to ongoing autoimmune disease.

Aging↗
PubMed1977

B-cell alloantigen associated with chronic mesangiocapillary glomerulonephritis.

Thirteen patients with chronic mesangiocapillary glomerulonephritis (M.C.G.) defined by light and immunofluorescent microscopy were examined for possible B-lymphocyte alloantigen associations by means of antisera from multiparous mothers of M.C.G. probands. Three such sera reacted with M.C.G.-patient B-cells. One of these sera (M.C.G.3) was highly discriminative for a B-cell antigen present in 77% of M.C.G. patients and only 17% of normal individuals tested. The risk of developing M.C.G. was estimated to be 16-6 times greater in the presence of the M.C.G.3 antigen than in its absence. This is the first demonstration of an association between a specific B-lymphocyte determinant and immune-mediated glomerulonephritis.

Adult↗
PubMed1977

Systemic lupus erythematosus within the first two decades of life.

Forty-nine patients with systemic lupus erythematosus (SLE) during childhood and adolescence presenting over a period of 17 years were followed during treatment with prednisone and azathioprine. The average period of follow-up was 5.7 years. Detailed analyses of clinical parameters of renal function and sequential changes in glomerular abnormalities by percutaneous renal biopsy are reported. Therapy was directed towards normalizing the results of urinalysis and renal function, eliminating proteinuria and maintaining normal serology (normal serum complement and negative antiDNA titers). The 10 year survival of the entire group was 86 per cent. A survival of 73 per cent and 87 per cent over this interval in patients with diffuse and focal proliferative lupus nephritis, respectively, was achieved. The major cause of mortality in this series was infection. It appears that intensive observation and monitoring of serologic parameters in SLE, along with aggressive steroid and immunosuppressive therapy, lead to a prognosis in SLE more favorable than previously reported.

Adolescent↗
PubMed1977

Postpubertal evaluation of gonadal function following cyclophosphamide therapy before and during puberty.

Evaluation of pituitary gonadotropins, gonadal steroids, spermatogenesis, and menstrual function was undertaken in 32 patients (19 males and 13 females) treated with cyclophosphamide because of nephrotic syndrome. Patients were treated before, during, or after puberty. Evaluations took place after or in very late puberty. Spermatogenic dysfunction occurred in six of 15 boys who received the entire course before and during puberty and was probably dose related. Menstrual dysfunction did not occur following treatment of six prepubertal or pubertal girls, though only low total doses were used. Therapy after puberty was associated with spermatogenic dysfunction in all four boys, but did not cause menstrual dysfunction in any of seven women. Tentative guidelines are suggested that many minimize gonadal toxicity when cyclophosphamide is used in children with nephrotic syndrome. Factors of particular importance in the interpretation of gonadotropin determinations and of sperm counts in young cyclophosphamide-treated patients are discussed.

Cyclophosphamide↗
PubMed1977

Unilateral Shwartzman reaction: cortical necrosis in one kidney following in vivo perfusion with endotoxin.

Unilateral renal cortical necrosis was selectively induced by in situ perfusion of the rabbit kidney with a perfusate containing 50 microgram of endotoxin followed by the i.v. administration of 250 microgram of endotoxin 24 hr later. The results strongly support the idea that the initial event in the genesis of renal cortical necrosis during the Shwartzman reaction is a specific local effect of endotoxin on the vascular endothelium.

Animals↗
PubMed1977

Polyanion and complement receptor of the glomerular epithelium. Relationship to pH.

Two markers on the surface of glomerular epithelial cells were studied on human and rat tissue. The glomerular polyanion is known to be a sialoglycoprotein present profusely on glomerular epithelial cell surfaces, and it is detected by binding with cationic dyes. This staining is lost after incubation in the pH range 3.8 to 4.4, yet retained at a more acidic or physiologic pH. A receptor for complement is also present on human glomerular epithelial cells. This receptor is also lost as a function of varying pH incubation and this loss parallels the pattern observed for glomerular polyanion. Neuraminidase treatment of renal tissue removes the sialic acid-dependent glomerular polyanion staining but preserves and stabilizes the complement receptor. Both functions are markers of the cell surface of glomerular epithelial cells and behave as peripheral membrane proteins.

Animals↗
PubMed1977

Breakdown products of C3 and factor B in hemolytic-uremic syndrome.

Serum concentrations of Clq, C4, C3, and Factor B but not properdin were significantly decreased in patients with HUS compared to values in normal control subjects (p value less than 0.01). Sera from 13 HUS patients obtained early after the onset of the disease showed breakdown products of Factor B (Ba, Bb) by immunoelectrophoresis; 12 of these sera showed C3 breakdown products (C3c, C3d). Sera from seven patients studied 1 month to 3 years later no longer demonstrated any breakdown products of Factor B or C3. These data suggest that the complemented system is activate in HUS. The concept that immunological mechanisms play a major role in this disease is additionally supported by the occurrence of IgM, C3, and fibrin in glomeruli and renal vessels.

Adolescent↗