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Biomedical subjects

R L Vernier

Publications and source records attributed to R L Vernier.

At least 55 records · Page 3Linked to original sources
PubMed1981

Membranous glomerulonephropathy and nephrotic syndrome associated with iatrogenic metallic mercury poisoning in a cat.

The nephrotic syndrome, characterized by nonselective proteinuria, hypoproteinemia, hypoalbuminemia, and ascites, was observed in a 10-month-old male cat. Profound glomerular changes and renal tubular changes appear to have been induced by iatrogenic chronic exposure to metallic mercury originally contained in a rectal thermometer. Large concentrations of mercury were present in the kidneys, liver, spleen, and urine. Evaluation of glomeruli by immunofluorescent microscopy revealed interrupted granular deposition of immuno-globulin G and the third component of complement in glomerular capillary walls and the mesangium. Electron microscopic evaluation of glomeruli revealed diffuse alterations in glomerular basement membranes and visceral epithelial cells. Small electron dense deposits were observed in capillary walls, but they were not characteristic of immune complexes. The mechanism(s) responsible for the mercury induced glomerulonephropathy in this patient could not be determined on the basis of available data.

Animals↗
PubMed1980

Methods for immunoelectron microscopy: Localization of antigens in rat kidney.

This study evaluated a variety of fixatives and methods of tissue preparation for application of the direct peroxidase-labeled antibody technique to rat kidney specimens. Tissue ultrastructure was most satisfactorily preserved and the antigens studied (rabbit IgG, human IgG, and rat Tamm-Horsfall protein (THP) were adequately preserved after brief fixation with 1% glutaraldehyde (15 min), a mixture of paraformaldehyde (1%) and glutaraldehyde (0.05%), or a paraformaldehyde, lysine, periodate fixative. Glycerol substitution was considered an important step which minimized ice crystal artifacts. Freezing and thawing were essential steps that facilitated adequate penetration of labeled antibody to specific antigenic sites. The distribution of injected rabbit IgG (anti-rat glumorular basement membrane (GBM) antibody) was predominately on the lamina rara interna and externa of the GBM. Injected aggregated human IgG was found primarily within the spaces between glomerular mesangial cells. Rabbit anti-rat THP was localized primarily on the infolding membranes of cells of the ascending thick limb of Henle. We suggest that the methods described may have wide application.

Animals↗
PubMed1980

Immunologic kidney disease.

Immunologically mediated renal diseases include Goodpasture's syndrome, systemic lupus erythematosus, membranoproliferative glomerulonephritis, membranous nephropathy, poststreptococcal glomerulonephritis, IgA-IgG nephropathy and anaphylactoid purpura. In Goodpasture's syndrome, antibodies are directed against the glomerular capillary basement membrane. The other disorders appear to result from circulating immune complexes which deposit in glomerular capillary walls or in the glomerular mesangium. Treatment with steroids and/or immunosuppressives is effective in lupus nephritis; in other diseases, the results are less certain.

Anti-Glomerular Basement Membrane Disease↗
PubMed1980

Immunoelectron microscopy of the glomerular mesangial uptake and transport of aggregated human albumin in the mouse.

The uptake and disposal of injected aggregated human albumin (AHA) by the glomerular mesangium of normal mice was evaluated by immunoelectron microscopy. The injected AHA rapidly entered the mesangial matrix channels via endothelial fenestra at the axial pole of the lobules and reached maximal concentrations at 8 hours after injection. Small quantities of AHA were endocytosed by mesangial cells. Significant filtration of the polydispersed AHA, which included molecular albumin, was observed across both the peripheral glomerular basement membrane and the mesangial glomerular basement membrane. The injected AHA was observed in the juxtaglomerular region, between lacis cells, and in the wall of arterioles at early time periods after injection. A heavy fraction of AHA (molecular weight, greater than 1 million) was also readily taken up by the region and was found in the interstitial space in the vicinity of glomeruli at 2 1/2 hours after injection. This study demonstrates a method for sequential study of the distribution in the kidney of protein macromolecules of great biologic significance. The study confirms the existence of an efferent limb of mesangial drainage to the region of the juxtaglomerular region and the renal interstitium. The fact that very large aggregates readily transited this pathway and were found in the interstitial space offers additional support for the hypothesis that the renal lymphatics may participate in the clearance of macromolecules from the glomerular mesangium.

Animals↗
PubMed1980

Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse.

Intact and uninephrectomized genetically diabetic (db/db) mice (C57BL/KsJ) and their nondiabetic littermates (dm/m) had renal biopsies performed at 6 months of age. Renal tissues were studied by regular light microscopy and by a variety of immunohistochemical techniques. Intact db/db mice had peripheral mesangial thickening as compared to db/m mice. This thickening, predominantly due to increased mesangial matrix material, extended to the glomerular hilum and the extraglomerular mesangium of the juxtaglomerular apparatus. This abnormality was markedly increased an uninephrectomized db/db mice (db/db-UN) compared to intact db/db mice. Db/m-UN animals had slightly greater mesangial thickness than intact db/mice but less than that of db/db mice. Intact db/db mice had increased mesangial IgM staining compared to db/m mice and these differences were magnified by uninephrectomy. The IgM staining, especially in the diabetic mice, involved the peripheral mesangium and the glomerular hilum extending into extraglomerular mesangium and the distal tubule at the level of the macula densa. The tubular staining in the region of the juxtaglomerular apparatus was between the tubular basement membrane and the epithelial cells and between epithelial cells. The distal tubular epithelial cell cytoplasm also showed increased staining for IgM as the tubule coursed away from the glomerulus. These studies amplify the argument that alterations in glomerular hemodynamics influence the rate of development of diabetic glomerular lesions. Further, these diabetic mice appear to represent an important model for the study of mesangial macromolecular processing mechanisms.

Animals↗
PubMed1979

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↗
PubMed1979

Tamm-Horsfall glycoprotein: ultrastructural immunoperoxidase localization in rat kidney.

Tamm-Horsfall urinary glycoprotein (TH) is the primary constituent of urinary casts. The intracellular distribution of TH in normal rat kidney was determined by immunoelectron microscopy using horseradish peroxidase-labeled antibodies and compared with morphologic localization of TH by immunofluorescence and light immunoperoxidase microscopy. Electron microscopy revealed an intracellular localization of TH restricted to the thick ascending limb of the loop of Henle (ALH). In this nephron segment, TH was distributed on and between adjacent intercellular membranes and infolding intracellular membranes at the base of these cells, within Golgi vacuoles, apical vesicles, and on the luminal membranes. Macula densa cells were negative, although typical ALH cells across the lumen of the same tubular segment were positive. Other renal segments were negative for intracellular TH. The unique distribution of TH is consistent with the known function of the ALH as the diluting segment of the nephron. We speculate that the aggregation and gel formation of TH on and between ALH surface membranes may restrict water movement across the ALH. This influence on permeability would be an important role for TH in the generation of concentration gradients for the countercurrent multiplier system of the kidney.

Animals↗
PubMed1978

Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. V. Fixed glomerular antigens in the pathogenesis of heterologous immune complex glomerulonephritis.

In heterologous immune complex glomerulonephritis glomerular deposition of immune complexes occurs immediately after an injection with heterologous antibody directed against antigen, derived from the brush border of the tubules. The injected antibody is thought to combine with circulating Fx1A antigen to form immune complexes which subsequently are deposited in the glomeruli. However, perfusion of rat kidneys in absence of this antigen likewise resulted in prompt localization of immune complexes along the glomerular basement membrane. Further, Fx1A antigen was shown to be present in the capillary wall, especially in the filtration slits and on the cell membrane of epithelial cells. From these findings it was concluded that in this model of glomerulonephritis the deposited immune complexes are formed locally instead of being deposited from the circulation. This concept of "fixed antigen" may also be relevant to the pathogenesis of other forms of experimental glomerulonephritis and probably also for human glomerulonephritis.

Antigen-Antibody Complex↗
PubMed1978

Tamm-Horsfall protein. Abnormal localization in renal disease.

Interstitial deposits of periodic acid-Schiff positive fibrillar material have been detected in a variety of diseases associated with tubulointerstitial pathology. This material has been shown to be Tamm-Horsfall protein by immunofluorescent, immunochemical, and electron microscopic studies. Prospective evaluation of 133 kidneys revealed deposits in 11 per cent. These deposits included medullary cystic disease (50 per cent), obstructive uropathy and vesicoureteral reflux (21 per cent), and tubulointerstitial disease (29 per cent). Tamm-Horsfall protein was also detected in Bowman's space in four cases of obstructive uropathy. It is proposed that these deposits result from severe tubular damage with release of Tamm-Horsfall protein from its normal intracellular and intralumenal locations into the renal interstitium. We speculate that the intersitial deposition of this sequestered protein may result in a continued inflammatory response and progressive renal damage.

Fluorescent Antibody Technique↗
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

The association of familial liver disease, subepidermal immunoproteins, and membranoproliferative glomerulonephritis.

Herein we report a new familial form of hepatic disease. Each of the four patients had splenomegaly, hypersplenism, a small liver, biochemical evidence of hepatic excretory dysfunction and hepatocellular damage, kidneys without demonstrable cysts, and normal blood pressue. An evaluation of serum immunoproteins, autoantibodies, histocompatibility antigens, and mixed lymphocyte reactivity further defined the immunologic features of this syndrome. Extrahepatic manifestations included a papulosquamous dermatitis with deposition of immunoglobulins and complement in both normal and abnormal skin, a membranoproliferative glomerulonephritis with subendothelial deposits, arthritis, and pericardial, pleural, and synovial effusions.

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↗