Role of antibody to S100 protein in diagnostic pathology.
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Animals↗
Biomedical subjects
R Baumal
Publications and source records attributed to R Baumal.
Lectin binding by liver and lung metastasizing variants of the murine Lewis lung carcinoma.
Lectin binding was assessed in subcutaneous tissues of 9 primary tumors of liver and lung metastasizing variants of murine Lewis lung carcinoma (LLC) and their metastases, using the avidin-biotin peroxidase technique. Dolichos bifloris agglutinin, concanavalin A, Ricinis communis agglutinin, and wheat germ agglutinin bound to equal numbers of primary and metastatic tumor cells, indicating that the carbohydrate moieties detected by them were not associated with metastatic potential. However, with peanut agglutinin (PNA), soybean agglutinin (SBA), and Ulex europaeus agglutinin I (UEA-I), the majority of primary tumor cells had the phenotype PNA-, SBA-, UEA-; metastatic tumor cells to the liver had the phenotype PNA+, SBA+, UEA-1-, and metastases to lung had the phenotype PNA+, SBA+, UEA-1+. Thus, LLC tumor cells that were PNA+ SBA+ had metastatic potential, but with no organ-specific preference. However, those that were UEA-I- or UEA-I+ preferentially metastasized to the liver and lung, respectively, implying that selective metastasis was associated with differences in the carbohydrate composition of metastatic tumor cells.
Animals↗
Safety and efficacy of long-term treatment with inhaled beclomethasone dipropionate in steroid-dependent asthma.
An open long-term trial of inhaled beclomethasone dipropionate was carried out in 32 asthmatic patients chronically dependent on systemic corticosteroids. Our objectives were to study the efficacy and safety of beclomethasone and to determine the proportion of patients in whom systemic steroids could be replaced by the new drug. All subjects had a clear history and physical findings of asthma as well as significant improvement in respiratory function after inhalation of salbutamol. Patients were followed for 4 to 8 years. Compared with a baseline period, patients receiving beclomethasone had reduced symptoms and needed less bronchodilator therapy, but their pulmonary function was unchanged. Bronchial biopsy specimens from seven patients who had been taking beclomethasone for as long as 8 years did not differ histologically from specimens from five asthmatic patients who had never taken the drug. Nine patients were able to stop taking systemic corticosteroids within 9 months, eight required them occasionally, and in eight the requirement was substantially reduced; the requirement did not change appreciably in the remaining seven. Inhaled beclomethasone is a safe and effective drug for chronic administration to asthmatic patients, and in 78% of our subjects the need for systemic steroids was substantially reduced or eliminated.
Administration, Inhalation↗
Quantitation of anionic sites in glomerular capillary basement membranes of Samoyed dogs with hereditary glomerulopathy.
Samoyed hereditary glomerulopathy (SHG) is an X-linked dominant disease characterized by proteinuria and renal failure in affected male dogs. Electron microscopic examination of glomerular capillary basement membranes (GCBM) shows widespread multilaminar splitting of the lamina densa, identical to that in Alport's syndrome. Anionic sites in GCBM of three affected males and five unaffected dogs were labeled using polyethyleneimine to determine whether proteinuria was associated with an alteration in their number. No significant differences were noted in the number of anionic sites in the lamina rara externa, whereas small but statistically significant increases were seen in the number of sites in the lamina rara interna of affected males. In the lamina densa, affected males showed a striking increase in anionic sites, particularly in regions of GCBM which were split. Thus, although proteinuria in some glomerular diseases has been attributed to a reduction in anionic sites in GCBM, this was not so in SHG.
Animals↗
Cyclosporin A in children with persistent renal transplant rejection and progressively deteriorating graft function.
The effect on renal function and growth of switching from azathioprine to cyclosporin A (CyA) was prospectively evaluated in ten children with persistent renal transplant rejection. Progression of renal insufficiency during CyA therapy was compared with that before using CyA. Prednisone administration decreased after CyA was introduced and although growth retardation persisted, height velocity improved significantly. Renal function stabilized in seven patients treated with CyA for a variable time period, and four of these children remain off dialysis 0.44-1.42 years later. Renal biopsies were obtained in seven children when they were converted from azathioprine to CyA. The response to CyA could not be predicted from renal morphology or clinical features.
Adolescent↗
Clinical significance of renal biopsies showing mixed mesangial and global proliferative lupus nephritis.
Renal biopsies of 70 children with systemic lupus erythematosus were categorized, according to the World Health Organization classification, as normal (five, 7%), mesangial (23, 33%), focal segmental proliferative (11, 16%), diffuse global proliferative (20, 29%) (ie, greater than or equal to 80% of glomeruli showing mesangioendothelial cell proliferation and/or deposition of immune complexes along the subendothelial margin of glomerular capillaries), and membranous (six, 8%) lupus nephritis (LN). In addition, five (7%) biopsies showed global proliferative LN in less than 80% of glomeruli and mesangial LN in the others. We assessed the renal status of these five patients at the time of renal biopsy and at outcome following prednisone treatment, with or without azathioprine. Four patients improved and later had either a normal urinalysis or only trace proteinuria. A low chronicity index was calculated on the biopsies of these patients. The fifth patient, whose condition did not improve, demonstrated a high chronicity index on renal biopsy. Overall, the renal status at outcome in the patients showing mixed mesangial and global proliferative LN more closely resembled that of patients with mesangial than diffuse global proliferative LN.
Biopsy↗
Lectin histochemistry of Wilms' tumor. Comparison with normal adult and fetal kidney.
The lectin histochemical staining patterns of nine surgically resected Wilms' tumors (WIT) (five classical, one rhabdomyomatous, one monomorphic tubular, and two blastematous) and four WIT heterotransplants in nude mice were compared with those of six normal adult and fetal kidneys using 11 biotinylated and fluorochrome-labeled lectins representing a spectrum of sugar specificities. Tubular epithelial cells of fetal and adult kidney demonstrated a complex pattern of glycosubstances, as detected by staining with most of the lectins. The dysplastic tubules of WIT and WIT heterotransplants resembled distal convoluted tubules and collecting ducts of adult kidney, as detected by staining with lectins that reacted exclusively with these portions of the nephron. A simpler lectin affinity profile was observed with blastema of normal fetal kidney and blastema of WIT and WIT heterotransplants. Thus, fetal, adult, and tumor tubules and fetal and tumor blastema resemble each other in terms of lectin binding patterns.
Adult↗
Characterization of binding of four monoclonal antibodies to the human ovarian adenocarcinoma cell line HEY.
Four mouse monoclonal antibodies (mAb) (10B, IgG1; 8C, IgG2a; M2A, IgG2a; M2D, IgG2b) were characterized with respect to their binding to the ovarian adenocarcinoma cell line HEY, using displacement assays and Scatchard plot analyses. The four mAb reacted with different antigens on the surface of HEY cells, with affinity constants ranging from 1 X 10(9) to 3 X 10(9) M-1. The number of binding sites per cell for each antibody was approximately 2 X 10(4). mAb 8C and M2D remained associated with the cell surface following binding to their respective antigens, while mAb 10B was rapidly internalized, with 50% of the bound mAb being lost from the cell surface during 4 h of incubation at 37 degrees C. These different binding characteristics of the mAb may influence their ability to target radioactivity and cytotoxic drugs to HEY cells.
Adenocarcinoma↗
Demonstration by light microscopy of cytomegalovirus on a renal biopsy of a renal allograft recipient: confirmation by immunohistochemistry and in situ hybridization.
A 14-year-old boy with end-stage renal failure secondary to reflux nephropathy received a renal transplant and was immunosuppressed with prednisone, azathioprine, and Minnesota antilymphoblast globulin, followed by cyclosporine A. A renal biopsy was performed 43 days post-transplantation because of fever and an elevated serum creatinine. The biopsy showed a mild interstitial lymphocytic infiltrate and immunosuppression was not changed. A second renal biopsy was performed 66 days after transplantation because of a persistent elevation of the serum creatinine following a cytomegalovirus (CMV) infection. CMV inclusions were seen by light microscopy (LM) in glomerular and peritubular capillary endothelial cells and tubular epithelial cells but no viral inclusions were present on the grids examined by electron microscopy (EM). However, the inclusions seen by LM were confirmed as CMV by immunohistochemistry, using polyclonal and monoclonal antibodies to CMV, and by in situ hybridization, using a biotinylated CMV DNA probe, emphasizing the usefulness of these techniques when studies by EM are not contributory.
Adolescent↗
Scanning electron microscopy of cellular and acellular glomeruli of male dogs affected with Samoyed hereditary glomerulopathy and a carrier female.
Glomeruli isolated from three male dogs affected with Samoyed hereditary glomerulopathy were compared by scanning electron microscopy with glomeruli of one carrier female and six unaffected dogs. Scanning electron microscopy was performed before and after removal of podocytes and endothelial cells with enzyme and detergent, producing cellular and acellular glomeruli respectively. Cellular glomeruli of unaffected dogs showed podocytes with normally arranged foot processes, while in acellular glomeruli, the subepithelial surface of glomerular capillary basement membranes appeared smooth to finely granular. In contrast, cellular glomeruli of affected males showed microvilli, globular cytoplasmic projections from podocytes, and effacement of foot processes; acellular glomeruli demonstrated ridges and plaque-like irregularities on the subepithelial surface of glomerular capillary basement membranes. Changes in the glomeruli of the carrier female were intermediate between those of unaffected and affected male dogs. The appearance of the subepithelial surface of glomerular capillary basement membranes of acellular glomeruli seen by scanning electron microscopy correlated with the extent of multilaminar splitting of glomerular capillary basement membranes seen by transmission electron microscopy.
Animals↗
Samoyed hereditary glomerulopathy. Immunohistochemical staining of basement membranes of kidney for laminin, collagen type IV, fibronectin, and Goodpasture antigen, and correlation with electron microscopy of glomerular capillary basement membranes.
Recent immunofluorescence studies on the kidneys of most males with hereditary nephritis have demonstrated an absence of Goodpasture antigen (GPA) from glomerular capillary basement membranes (GCBM). In the present study, we used immunofluorescence to determine whether laminin, collagen type IV, fibronectin, and GPA could be detected in basement membranes of the kidneys of dogs with Samoyed hereditary glomerulopathy, which was previously shown to be a model for human hereditary nephritis. The results obtained were correlated with the appearance of GCBM by electron microscopy (EM). The rabbit polyclonal antibodies used (antilaminin, anti-collagen type IV, and antifibronectin) showed specificity for the appropriate antigens in a plate-binding radioimmunoassay. Serum from a patient with Goodpasture syndrome was used to detect the GPA component of dog GCBM. Laminin and collagen type IV were present in GCBM, mesangium, tubular basement membrane, vascular basement membrane, and Bowman's capsule of neonatal, unaffected, and affected male and carrier female dogs. Fibronectin was present in mesangial, perivascular, and interstitial regions of the kidneys of all dogs and, in addition, in GCBM of neonatal, affected male, and carrier female dogs. GPA was not detected in the kidneys of neonatal dogs and its absence from GCBM correlated with their immature appearance by EM. However, a fully formed, trilaminar GCBM was observed by 3 weeks of age in unaffected, affected male, and carrier female dogs, before the detection of GPA in GCBM, which occurred at 4 weeks in unaffected and carrier female dogs, but still not in affected males. In the unaffected dogs, the presence of GPA correlated with the persistence of a fully formed trilaminar GCBM, which lasted throughout life, while in the carrier females, the presence of GPA correlated with focal areas of multilaminar splitting of GCBM by EM. In the affected male dogs, although a trilaminer GCBM was seen by 3 weeks of age, the persistent absence of GPA correlated with the eventual onset of multilaminar splitting of GCBM. These immunofluorescence and EM results suggest that GPA is not required to form a trilaminar GCBM initially but is necessary subsequently to maintain its integrity. GPA is normally present in the C terminal (NC1) domain of the collagen type IV molecule. It is hypothesized that Samoyed hereditary glomerulopathy in dogs and human hereditary nephritis result from a defect in the NC1 domain.
Animals↗
Samoyed hereditary glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies.
Human hereditary nephritis refers to familial glomerular diseases which may progress to renal failure. Samoyed hereditary glomerulopathy has been shown previously to be a model for hereditary nephritis. Clinical and laboratory studies were performed to follow progression to renal failure in 44 dogs in a family with Samoyed hereditary glomerulopathy. Affected males appeared healthy for their first three months but then became progressively wasted. Proteinuria was detected between two to three months of age; after five months, urine protein electrophoresis showed pre-albumin, albumin and alpha and beta globulin peaks. From three months onward, a reduced glomerular filtration rate was detected. Serum albumin decreased while amylase, urea, creatinine and phosphate increased from four to five months of age. Death from renal failure occurred by 15 months. Carrier females also became thinner and developed proteinuria between two and three months of age, but neither renal failure nor death ensured. Hence, SHG progressed rapidly in affected males but not in carrier females.
Animals↗
Naproxen-associated renal failure in a child with arthritis and inflammatory bowel disease.
Renal failure occurred in a 14-year-old girl with peripheral arthritis associated with inflammatory bowel disease while she was being treated with naproxen. She had previously received aspirin and tolmetin sodium and had no complications. A renal biopsy showed a severe tubulointerstitial nephritis. Although her renal function improved somewhat with corticosteroid treatment, it worsened when the steroids were discontinued. This case emphasizes that renal failure can develop insidiously in children on nonsteroidal anti-inflammatory drug therapy and that such children must be monitored closely for signs of nephrotoxicity.
Adolescent↗
Regulation of renal sulfoglycolipid biosynthesis.
The in vitro activity of the renal galactolipid sulfotransferase and the level of sulfated glycolipids in the rat kidney have been correlated as a function of age. The galactolipid sulfotransferase was found to be greatly reduced in the young as compared with the adult animal. The relatively minor changes in the sulfated glycolipid content of the kidney with age suggests that an increase in sulfoglycolipid turnover occurs during growth. An inhibitory activity was detected in the homogenate supernate of the young animal capable of reducing the in vitro sulfotransferase activity of the adult. Assay of the human renal galactolipid sulfotransferase showed that this enzyme activity is deleted in samples of the blastematous form of Wilm's renal tumor. The results suggest that the rate of synthesis of renal sulfoglycolipids may prove a marker of renal development, perhaps by post translational regulation.
Aging↗
Malignant myoepithelioma of the breast. An immunohistochemical study by light and electron microscopy.
Myoepitheliomas of the breast are extremely rare; only four cases have been reported to date. It is not clear whether these tumors behave in a benign or malignant fashion, and no metastatic spread has been documented. We report a myoepithelioma of the breast with metastatic spread to an axillary lymph node. Myoepithelial cell (MEC) differentiation in the tumor was characterized using electron microscopic (EM) criteria. Immunologic investigations at the LM and EM levels showed that the tumor cells were positive for S100 protein, actin, and epidermal cytokeratin; these findings are indicative of MEC differentiation. By immuno-EM, cytokeratin filaments were present in a perinuclear location, while actin filaments were concentrated along the cell periphery. To the authors' knowledge, this is the first report of a breast myoepithelioma that has metastasized and also the first report of the immunologic characterization of a myoepithelioma at the light and electron microscopic levels.
Aged↗
Nephrotic syndrome and hypertension in two children with Hurler syndrome.
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Child, Preschool↗
Role of immunohistochemistry in the diagnosis of undifferentiated tumors involving the skin.
Twenty undifferentiated skin tumors were examined by immunostaining in an attempt to achieve more precise identification. Light microscopy yielded only a differential diagnosis, whereas immunostaining of formalin-fixed, paraffin-embedded tissue sections with a panel of antibodies to intermediate filaments and other cell components led to a definitive diagnosis. Four cytokeratin-positive epithelial tumors were subtyped into squamous cell carcinomas and adenocarcinomas with the use of antibodies to different cytokeratin polypeptides. Fifteen vimentin-positive tumors were subdivided into malignant melanomas with the use of antibody to S-100 protein, lymphomas with the use of antibody to immunoglobulin, and mesenchymal tumors (angiosarcomas, atypical fibroxanthomas, dermatofibrosarcoma protuberans, and meningiomas) with the use of antibody to S-100 protein, factor VIII, and lysozyme. One desmin-positive tumor was diagnosed as a leiomyosarcoma of the skin. A scheme is presented for using immunohistochemistry to facilitate the diagnosis of undifferentiated tumors involving the skin.
Antibodies↗
Correlation of renal histology with outcome in children with lupus nephritis.
We assessed renal histological features in 20 children with diffuse proliferative lupus nephritis (DPLN) to determine whether they were useful in predicting clinical outcome. Renal biopsies were analyzed by assigning scores indicating an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis, serum creatinine, need for dialysis and/or transplantation, and/or death from end-stage renal failure. Renal function at biopsy correlated significantly with AI and CI. Serum complement (C3 and C4) correlated significantly with CI but not with AI. The usefulness of the clinical grading system was confirmed in ten patients who underwent repeat biopsies. Of these, four converted from DPLN to mesangial or membranous lupus and showed improvement in their grade, while only one of the six with DPLN on both biopsies improved. After a mean follow-up of 4.0 years, 14 of the 20 patients showed clinical improvement, four were unchanged, and two were worse. CI predicted clinical outcome (P less than 0.01) but AI did not. Histologic scores of AI and CI obtained from renal biopsies showing DPLN may be useful in predicting therapeutic responses and designing prospective clinical trials to determine optimum management of children with DPLN.
Adolescent↗