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Biomedical subjects

R L Vernier

Publications and source records attributed to R L Vernier.

At least 37 records · Page 2Linked to original sources
PubMed1985

A clinicopathologic study of forty-eight infants with nephrotic syndrome.

The clinical and histopathologic features of 48 children presenting with the nephrotic syndrome during the first year of life were analyzed. Proteinuria was discovered soon after birth to 3 months of age in 39 infants (congenital nephrotic syndrome), and nine infants had an infantile onset presenting between 4 and 12 months of age. Neither histologic parameters--microglomeruli, epithelial, or mesangial proliferation, focal segmental or global sclerosis, fibrinoid necrosis, or tubular microcysts--nor histologic classification--microcystic disease, mesangial proliferative glomerulonephritis, focal segmental glomerular sclerosis/hyalinosis-predicted the outcome. Rather, age at presentation was found to predict outcome: One of 39 infants with a congenital onset and seven of nine infants with an infantile onset underwent a complete remission (P less than 0.0001).

Child, Preschool↗
PubMed1985

Localization and quantitation of anionic charge sites in fetal and neonatal alveolar basement membranes.

A method utilizing biopsy sized samples of lung for anionic charge site localization in alveolar and capillary basement membranes in human tissue is discussed. Tissue fixed in either paraformaldehyde-lysine-periodate or 1% paraformaldehyde with 0.05% glutaraldehyde, cut into 30 mu sections, and incubated with the cationic probe, polyethyleneimine, was processed for electron microscopic analysis using standard techniques. Anionic charge sites were identified and regularly distributed in increments of approximately 40-50 nm in the lamina rara externa of the alveolar basement membrane, with lesser amounts found in the lamina rara interna and lamina densa. Anionic charge sites were also demonstrated in the interstitial portion of the capillary basement membrane and on cell surfaces. These methods can be used to more broadly define the localization of anionic charge sites in human lung tissue in both normal and pathologic states.

Anions↗
PubMed1984

Congenital nephrotic syndrome: evolution of medical management and results of renal transplantation.

We analyzed the clinical course, pathologic findings, and results of aggressive medical management and renal transplantation in 41 infants with onset of nephrotic syndrome in the first 3 months of life. All but one infant with congenital onset failed to thrive and had progressive renal insufficiency; 17 were given steroids or cytotoxic drugs or both, without benefit. Severe bacterial infections occurred in 85% of the infants, pyloric stenosis in 12%, gastroesophageal reflux in 8%, and thrombotic events in 10%. All children prior to the era of renal transplantation died before 4 years of age. The last 24 infants received aggressive medical management, which allowed renal transplantation in 17. Two-year patient and graft survival rates were 82% and 71%, respectively. There was no recurrence of the nephrotic syndrome in the children who underwent transplantation. All but one surviving infants has had normal or accelerated growth, although mean height for the group is 3.1 SD below the mean. School and social performance has been normal in 80%. Thus intensive medical therapy combined with renal transplantation offers a very good opportunity for survival with an acceptable quality of life for infants with congenital nephrotic syndrome.

Child Development↗
PubMed1984

Acute glomerulonephritis. A clinical overview.

Acute glomerulonephritis is a syndrome characterized by the abrupt onset of hematuria often accompanied by proteinuria, hypertension, edema, and renal dysfunction. Acute glomerulonephritis can be subdivided into primary glomerular disease, postinfectious glomerulonephritis, and glomerulonephritis associated with systemic disease. With few exceptions, the underlying mechanism of acute glomerulonephritis is an immunologic one. To differentiate clinically the specific etiology of the glomerulonephritis, attention must be focused on the presence of signs or symptoms of systemic disease, changes in the environment of the patient, family history of renal disease, and recent history of infectious disease.

Adult↗
PubMed1984

Late recurrence of minimal lesion nephrotic syndrome.

Nephrotic syndrome recurred in 16 patients who had been free of the disease for an interval of 4 to 25 years. Their initial illness began in childhood and responded to adrenocorticosteroid therapy; in 10 patients it was associated with few changes on light microscopic examination of kidney biopsy specimens. The late recurrence also responded to steroids, and in only 1 patient did low-grade proteinuria persist after treatment. Renal biopsy specimens taken from 8 patients during late recurrence showed minimal-change nephrotic syndrome in 7 and focal segmental glomerulosclerosis in 1. Renal function remained normal in all patients. The late recurrence of minimal-change nephrotic syndrome has most of the features of that syndrome seen in the more typical childhood age group and should be managed similarly.

Adrenal Cortex Hormones↗
PubMed1984

Idiopathic immune complex glomerulonephritis in dogs with multisystem involvement.

Renal specimens obtained by biopsy and/or at necropsy from 4 dogs with nephrotic syndrome were studied using light, immunofluorescence, and electron microscopies. The glomerulonephritis observed in these dogs was considered an idiopathic immune complex glomerulonephritis associated with multisystem involvement because causes of glomerulonephritis in these dogs could not be established. Immunoglobulin A was observed in granular deposits in the mesangial and subendothelial regions of the glomeruli. The relationship of the clinical and pathologic features of this disease in dogs to various renal syndromes in human beings are described.

Animals↗
PubMed1984

A new glomerular antigen in passive Heymann's nephritis.

Within 20 min after i.v. injection or unilateral renal perfusion of rabbit anti-rat proximal tubular brush border antigens (RARFAXIA) into rats, fluorescence microscopy (FM) demonstrated rabbit IgG (RIgG) in a linear fashion along the endothelial region of the glomerular capillary walls. This finding was confirmed by immuno-electron microscopy (IEM) which revealed the presence of reaction product on the plasma membranes of the endothelial cells. Between 8 h and 26 days following i.v. injection of RARFXIA, granular subepithelial deposits of RIgG were demonstrated by FM and IEM, and the endothelial localization seen at earlier time periods was no longer present. In the later time periods after loss of RIgG from the endothelial region, a second injection of RARFXIA did not result in binding of IgG to this site suggesting loss of the antigen or impairment in antigen-antibody binding affinity. Evidence for depletion of endothelial binding antibody from the circulation was derived from passive transfer experiments, in which sera were harvested from rats either 20 min or 48 h following i.v. injection of RARFXIA-I125. When equivalent doses of these sera were perfused into kidneys of normal rats, minimal glomerular binding was demonstrated with sera obtained at 20 min, but no binding to the capillary wall was observed with sera obtained at 48 h. These observations demonstrate that immediately after the induction of passive Heymann's nephritis (PHN) with the complex polyclonal antibody to FXIA, an antigen-antibody reaction occurs along the endothelial region of the glomerular capillary and that later in the course of the disease in vivo, antibody binding to this site is abrogated. The relationship of this early event to the ultimate development of subepithelial deposits is unknown. This reaction may be a source of immune complexes which migrate through the glomerular basement membrane (GBM) or the early binding of the antibody to an endothelial antigen(s) may result in altered permeability of the glomerular capillary allowing other antibodies to find their putative antigen(s).

Animals↗
PubMed1984

Shwartzman reaction in streptozotocin-induced diabetic rats.

The possibility that experimental diabetes could prepare for the generalized Shwartzman reaction was investigated in female Sprague-Dawley streptozotocin-induced diabetic rats. After 48 hours, 1 week, and 9 weeks of diabetes, the rats were injected with 2 mg/kg of endotoxin, and the animals were sacrificed 2, 4, 8, and 24 hours after endotoxin. Ninety percent of the diabetic animals given endotoxin developed massive glomerular capillary fibrin deposition accompanied by marked decrease in platelet count. The age- and sex-matched nondiabetic control rats had no such changes. This marked susceptibility to endotoxin, previously only reported in pregnant rats, was present as early as 1 week of diabetes. The degree of glycemic control greatly influenced the susceptibility of diabetic rats to the generalized Shwartzman reaction. Only 28% of the diabetic animals given insulin once daily (4.6 +/- 0.3 units, mean +/- SEM) and maintaining a blood glucose level of 269 +/- 19 mg/dl developed glomerular thrombi. In contrast, the diabetic animals that did not receive insulin and had a blood glucose level of 617 +/- 21 mg/dl all developed fibrin thrombi. We conclude that the diabetic state in rats induces a unique susceptibility to the generalized Shwartzman reaction following a single injection of endotoxin, which varies with the severity of the diabetic state. Although the pathogenesis is unclear, this phenomenon may reflect abnormalities in the glomerular capillary wall and/or the coagulation system that may be important in the development of microvascular complications. Furthermore, this phenomenon may, in the animal model, mirror the increased risk of the diabetic patient to intravascular coagulation with bacterial sepsis.

Animals↗
PubMed1983

Heparan sulfate--rich anionic sites in the human glomerular basement membrane. Decreased concentration in congenital nephrotic syndrome.

Recent work suggests that the normal barrier to penetration of the renal glomerular basement membrane by anionic plasma proteins may depend in part on the existence of negatively charged sites within the membrane. We describe an in vitro cytochemical method for the quantitative demonstration of anionic sites in the normal human glomerular basement membrane. In five normal subjects, ranging in age from 10 days to 57 years, the sites were distributed at regular intervals in the lamina rara externa, with a frequency of 23.8 +/- 6.8 sites per 1000-nm length of membrane. A similar distribution was observed in the basement membranes from three normal human fetuses. Ex vivo perfusion of one cadaver kidney revealed a similar distribution of anionic sites. The number of anionic sites in the glomerular basement membranes of five patients with the congenital nephrotic syndrome was reduced to 8.9 +/- 3.7 (P less than 0.001). Prior incubation of sections of normal kidney in purified heparinase resulted in a marked reduction in the number of anionic sites. We conclude that congenital nephrosis results from failure of heparan sulfate--rich anionic sites to develop in the lamina rara externa of the glomerular basement membrane.

Anions↗
PubMed1983

Immunoelectron microscopy of IgA nephropathy.

The distribution of IgA, IgG, IgM, C3, and albumin in kidney biopsy specimens from 11 children and adults with recurrent gross and microscopic hematuria and IgA nephropathy and 7 control specimens were evaluated by the direct peroxidase-labeled antibody method and electron microscopy. Granular masses of reaction product (RP), representing IgA, IgG, IgM, and C3, were observed within the mesangial matrix of glomeruli from all patients with IgA nephropathy. Occasional smaller masses of IgA-RP and C3-RP were noted along the peripheral glomerular capillary loops, the tubular basement membranes, and within the interstitial matrix of some patients. Large amounts of IgA-RP and C3-RP were present within the walls of small renal arterioles of several patients. These observations support the concept that immune-complex deposits are involved in the pathogenesis of IgA nephropathy and suggest that vascular deposits may have a more important role in the progression of the disease in some patients.

Adolescent↗
PubMed1983

Absence of Goodpasture's antigen in male patients with familial nephritis.

The presence of Goodpasture's (GP) antigen in the glomerular basement membrane (GBM) of the kidney was evaluated by indirect immunofluorescence in nine patients with familial nephritis from five kindreds. The GP antigen was not detected in seven males but was present in an affected sister and mother, an unaffected brother, and 13 normal controls. The specificity of this finding in affected males is supported by the persistence of other GBM antigens identified by monoclonal antibodies. The lack of GP antigen in affected males and its persistence in related females with the disease suggests a possible X-linked dominant mode of inheritance. We propose that the absence of GP antigen leads to severe disease in the male, whereas its presence in related females is associated with mild disease.

Anti-Glomerular Basement Membrane Disease↗
PubMed1983

Prevention of the generalized Shwartzman reaction in pregnant rats by prostacyclin infusion.

The effects of prostacyclin infusion on endotoxin-induced generalized Shwartzman reaction were studied in pregnant rats. Four hours after administration of Escherichia coli endotoxin (0.4 mg) to pregnant rats on the 20th day of gestation, fibrin and platelet thrombi were observed in 72% of the animals. These findings were associated with a decrease in renal blood flow and glomerular filtration rate from 7.0 to 0.7 and 0.8 +/- 0.1 to 2.6 +/- 0.4 and 0.2 +/- 0.8 ml/minute, respectively (p less than 0.0001 and less than 0.05) and a decrease in platelet count (p less than 0.05). The infusion of prostacyclin, at a mean dose of 57 ng/kg/minute prior to and after administration of endotoxin strikingly inhibited the development of fibrin and platelet thrombi in glomerular capillaries (p less than 0.001). Despite hemodynamic changes which were similar to those in control animals, renal blood flow and glomerular filtration rate decreased from 7.2 +/- 0.2 and 0.9 to 2.9 +/- 0.03 and 0.3 +/- 0.1 ml/minute, respectively (p less than 0.001 and less than 0.025). In addition, the mean blood pressure decreased from 118 +/- 3.8 to 86 +/- 3.7 mm Hg (p less than 0.025), whereas the platelet count remained normal. We conclude that prostacyclin infusion prior to endotoxin administration significantly inhibits endotoxin-induced generalized Shwartzman reaction in pregnant rats.

Animals↗
PubMed1983

The effect of charge on the renal distribution of ferritin.

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.

Animals↗
PubMed1982

Diabetic glomerulopathy in the uninephrectomized rat resists amelioration following islet transplantation.

Uninephrectomy is known to accelerate the development of both functional and morphological changes seen with experimental diabetic nephropathy in the rat. The present experiments utilized electron and light microscopic morphometric techniques to assess glomerular basement membrane width and the volumes of the total mesangium and its cellular and matrix components of inbred Lewis rats made diabetic at 6 weeks of age and uninephrectomized 9 days later. Immunofluorescent microscopy was used to evaluate IgG and C3 in the mesangium. The reversibility of established diabetic glomerular lesions in uninephrectomized diabetic rats after 7 months of diabetes was studied by performing intraportal transplant of neonatal pancreatic tissue. Renal biopsies were taken 2 months later in transplanted and non-transplanted animals. Islet transplantation lowered plasma glucose to normal levels (29.6 to 7.3 mmol/l) and raised plasma insulin values (6.3 to 53 muU/I). Glomerular basement membrane width in transplanted rats (268 nm) still exceeded the same measure (226 nm) in nondiabetic uninephrectomized rats. In transplanted animals volumes of the mesangium (0.51 x 10(6) micrometers 3) and of its cellular (0.27 x 10(6) micrometers 3) and matrix (0.24 x 10(6) micrometers 3) components remained higher than similar measures in control rats (0.32 x 10(6), 0.17 x 10(6) and 0.15 x 10(6) micrometers 3, respectively). Mesangial IgG in treated animals approached normal, but mesangial C3 remained similar to levels in non-transplanted diabetic control animals. These observations in uninephrectomized-diabetic rats contrast with previous observations in intact diabetic rats in which mesangial volumes and localization of immunoglobulins and complement returned to normal levels following islet transplantation.

Animals↗