Search PubMed⌕ Search

Biomedical subjects

B Noble

Publications and source records attributed to B Noble.

At least 73 records · Page 4Linked to original sources
PubMed1986

Reabsorption of horseradish peroxidase by proximal tubules in rats with Heymann nephritis.

The distribution of the histochemical protein tracer, horseradish peroxidase, was studied in proximal tubules of rats with Heymann nephritis. Peroxidase reabsorption was substantially reduced in stage 2 of Heymann nephritis, a period during which the brush border of proximal tubules is severely damaged by specific antibodies. Impairment of the reabsorption function could not be attributed either to proteinuria or disturbances of proximal tubule metabolism and appeared to result from loss of microvilli. Recovery of brush border membrane morphology in stage 4 of Heymann nephritis was not accompanied by recovery of the normal capacity to reabsorb peroxidase. Functional deficits resulting from immunologic injury to proximal tubules in Heymann nephritis may persist despite waning of the anti-brush border antibody response and regeneration of the brush border of proximal tubule cells.

Animals↗
PubMed1986

A transition from proliferative to membranous glomerulonephritis in chronic serum sickness.

Chronic serum sickness glomerulonephritis was induced in rats by daily i.v. administration of bovine serum albumin (BSA). Previous studies have shown that the disease progresses through three discrete stages: mild, moderate and severe. The diffuse, proliferative necrotizing glomerulonephritis of severe chronic serum sickness, which is accompanied by a decreased glomerular filtration rate and increased glomerular permeability to macromolecules, has an inevitable fatal outcome. In the experiments reported here, BSA injections were discontinued at the transition from moderate to severe glomerulonephritis, a point which was identified by decreased sodium excretion. Retrospectively, rats could be divided into two categories. Some, called non-survivors, continued to exhibit sodium retention. Those animals progressed rapidly to end-stage renal disease and died within two weeks of the cessation of antigen injections. Others, called survivors, returned to sodium balance and remained alive for many months. The development of progressive membranous glomerulonephritis, with prominent spike formation and disappearance of glomerular hypercellularity, was noted in all survivors. That change in histopathology occurred in the absence of both circulating BSA and precipitating antibodies to BSA. The transition of proliferative to membranous glomerulonephritis was accompanied by partial recovery of glomerular function, although proteinuria persisted. Maintenance of severe proteinuria did not appear to depend on an active immunological process.

Animals↗
PubMed1985

Colocalization of [3H]muscimol and antisera to GABA and glutamic acid decarboxylase within the same neurons in monkey retina.

Two procedures have been used to test for the colocalization of different neuroanatomical gamma-aminobutyric acid (GABA)ergic markers within the same neurons in primate retina. First, sequential immunocytochemical processing of sections was done using antisera to glutamic acid decarboxylase and to GABA, and these antisera were visualized by peroxidase-antiperoxidase and fluorescein isothiocyanate techniques respectively. Colocalization of both antisera was found within the same neuron cell bodies. In the second experiment, immunocytochemical staining using GABA antiserum was performed on retinal tissue that had been previously incubated in vitro for neuronal uptake of [3H]muscimol. Both markers colocalized in 70% of the labeled cell body population.

Animals↗
PubMed1985

Response of plasma proenkephalin peptide F to exercise.

Plasma proenkephalin Peptide F immunoreactivity was measured in the plasma of endurance trained and untrained males at various exercise intensities. Significantly different levels were found between the two groups at rest and at 54% maximum oxygen consumption (VO2 max). Maximum levels were at 5 min of recovery for the untrained group and at 54% VO2 max and at recovery 5 min for the trained group. These data suggest an adaptation in the trained group fro the release of this peptide and further suggest it may play a role in recovery since the highest levels are following the termination of the exercise period.

Adult↗
PubMed1985

Pathophysiology of the kidney in rats with Heymann nephritis.

Alterations in kidney function were assessed early in the course of Heymann nephritis that was induced in rats by immunization with Fx1A, an extract prepared from rat kidney cortex. Whole kidney and single nephron function were evaluated by clearance and micropuncture techniques. Kidney function was studied in stage 1 of Heymann nephritis, before the onset of proteinuria, and in stage 2, when antibodies are deposited along the brush border of proximal tubules. Although overall kidney function was similar in rats in stage 1 and normal controls, glucose reabsorption was somewhat depressed in the first part of the proximal convoluted tubule in stage 1. Both whole kidney and single nephron glomerular filtration rates were depressed in stage 2. Proteinuria in stage 2 was characterized by an increased albumin sieving coefficient, which resulted in an elevated excretion of albumin. Furthermore, several proximal tubule functions (glucose and fluid reabsorption and PAH extraction) were substantially depressed in stage 2. These findings demonstrate that immunological injury to the proximal tubules in stage 2 of Heymann nephritis produces a significant impairment of proximal function.

Albumins↗
PubMed1985

Changes in plasma proenkephalin peptide F and catecholamine levels during graded exercise in men.

Proenkephalin peptide F immunoreactivity, epinephrine, and norepinephrine were measured in the plasma of endurance-trained and untrained male subjects riding on a bicycle ergometer at 28%, 54%, 83%, and 100% of maximum oxygen consumption (VO2). At rest the trained group had peptide F levels almost twice the level of the untrained group, whereas all other variables measured were the same. The maximum epinephrine and norepinephrine levels were found at 100% exercise intensity, with a precipitous drop in the levels at 5 min of recovery. In contrast, the peptide F immunoreactivity reached a maximum at 5 min of recovery and was still substantially above the initial level after 15 min of rest. In addition, the trained subjects showed another peak of peptide F immunoreactivity at 54% VO2max. Possible explanations for the different patterns of catecholamine and peptide F levels are presented.

Adult↗
PubMed1985

Absence of sodium and water retention in rats with severe proteinuria.

Studies with two models of immunologically mediated glomerular disease in the rat, chronic serum sickness and Heymann nephritis, show that fluid retention can be dissociated from other signs of the nephrotic syndrome (excessive proteinuria, hypoalbuminemia, hypercholesterolemia). Clinical evidence of fluid retention (increased body weight, decreased hematocrit, ascites) was only detected in severe chronic serum sickness and coincided with an abrupt drop in urinary sodium concentration and sodium excretion. Severe proteinuria was not associated with sodium and water retention in moderate chronic serum sickness and in Heymann nephritis. These observations support the hypothesis that, in conditions of severe proteinuria, an intrarenal defect in sodium excretion rather than a systemic factor, leads to fluid retention.

Animals↗
PubMed1985

Proximal tubule function in chronic serum sickness glomerulonephritis of rats.

Fatal immune complex glomerulonephritis can be induced in rats by chronic intravenous administration of bovine serum albumin. There are three distinct stages, mild, moderate, and severe, in the development of renal immunopathology and pathophysiology in this model of chronic serum sickness. The work described here was undertaken to evaluate aspects of proximal tubule function in those different stages. Tissue water distribution, oxidative metabolism, and transport of representative organic anions and cations were measured in renal cortical slices. In mild chronic serum sickness all functions were normal except the transport of p-aminohippurate (PAH, organic anion), which was significantly decreased. This decrease appeared to be attributable to immunization with Freund's adjuvant. In the moderate stage of chronic serum sickness, proximal tubule functions and morphology appeared essentially normal. Only Na-K-ATPase activity was somewhat lower than in controls. However, proximal tubule dysfunction was a feature of severe chronic serum sickness. A significant inhibition of anion and cation transport was observed. Reduction in transport functions occurred together with impaired oxidative metabolism and severe reduction in Na-K-ATPase activity. Abnormalities of mitochondrial structure, a decrease in number of mitochondria, and a significant increase in intracellular H2O content provided additional evidence of degenerative changes in proximal tubule cells during the severe stage of chronic serum sickness. It was concluded that decreased transport of organic ions by the basolateral membrane in proximal tubules of rats with severe chronic serum sickness resulted from a breakdown in the metabolic machinery of the tubule epithelium rather than a specific injury to organic ion transport systems.

Animals↗
PubMed1985

Impaired organic ion transport in proximal tubules of rats with Heymann nephritis.

Organic ion transport across the basolateral membrane of proximal tubules was measured by means of the tissue slice technique in each of the four different stages of Heymann nephritis. Impairment of both organic anion and cation transport was detected early in Stage 2, and became more severe in Stage 3 of Heymann nephritis. The decreased transport function was associated with extensive damage to proximal tubule cells, including loss of brush border microvilli and basal infoldings. Despite these abnormalities of structure and function, oxygen consumption of proximal tubule cells remained essentially normal. Partial recovery of organic cation transport was noted late in Heymann nephritis (Stage 4). Recovery of the cation transport function was associated with a partial restoration of brush border microvilli and basal infoldings to proximal tubule cells. However, organic anion transport remained depressed throughout the entire course of disease. Impairment of organic ion transport in rats with Heymann nephritis appeared to result from damage to basolateral membrane transport elements rather than general deterioration of the metabolic machinery of proximal tubule cells. Decreased organic cation transport appeared to be the consequence of a reduction in the number of carrier sites, a phenomenon that could have resulted from decreased membrane surface area. However, the depression of organic anion transport was associated with decreased substrate affinity of the anion carrier, indicating that qualitative, rather than quantitative changes, were primarily responsible for that defect. Specific antibody-mediated damage to the anion transport elements in basolateral membranes of proximal tubules is postulated to occur in Heymann nephritis.

Adjuvants, Immunologic↗
PubMed1985

Antibody-induced redistribution of Heymann antigen on the surface of cultured glomerular visceral epithelial cells: possible role in the pathogenesis of Heymann glomerulonephritis.

In this study we analyze the ability of antibodies that produce passive Heymann glomerulonephritis to induce antigen redistribution on the surface of cultured glomerular visceral epithelial cells (GEC). Polyclonal antibodies produced by immunization with membrane vesicles prepared from proximal tubule brush borders (BB) and polyclonal (rabbit) and monoclonal (mouse) antibodies to a membrane glycoprotein (gp 330) purified from epithelial cells of rat proximal tubule were used. The study by immunofluorescence of GEC kept at 4 degrees C or fixed with paraformaldehyde showed that the three antibody preparations reacted with the plasma membrane in a punctate pattern known to be due to staining of coated pits or coated vesicles on the cell surface. At 37 degrees C and, at a slower rate, at 22 degrees C, the two polyclonal antibodies induced a rapid clustering of antigen-antibody complexes on the nonadherent surface of living cultured GEC with subsequent formation of patches and caps and, after prolonged incubation, with temporary disappearance of Heymann antigen from the cell surface, so-called antigenic modulation. Antigen redistribution and modulation were inhibited by sodium azide, indicating that these processes are energy dependent. Monovalent Fab fragments of antibodies to BB vesicles did not alter the distribution of Heymann antigen unless they were subsequently cross-linked. Monoclonal anti-gp330 induced a modest degree of antigen redistribution, which was increased by subsequent cross-linking. Exposure of glomerular epithelial cells to cytochalasin B, colchicine, or ionophore A23187 prevented or altered antigen redistribution at 37 degrees C. Furthermore, the antibody-induced antigen redistribution was associated with changes in distribution of cytoplasmic actin, myosin, and tubulin, indicating that it is related to the contractile activity GEC. LEW rats, given i.v. injection of IgG directed against BB membrane vesicles, developed passive Heymann glomerulonephritis (i.e., immune deposits in the lamina rara externa of the glomerular basement membrane). In contrast, the glomeruli of rats exposed for longer periods to larger amounts of Fab fragments of the same antibodies failed to develop immune deposits. These studies show that the antibodies to the nephritogenic antigen of Heymann glomerulonephritis may induce a redistribution of immune complexes (IC) in the membrane of glomerular epithelial cells that is similar to that produced by other plasma membrane antigen-ligand interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Factors influencing susceptibility of LEW rats to Heymann nephritis.

Although most LEW rats develop the proteinuria of Heymann nephritis (HN) within 2 months after immunization with Fx1A, protein excretion of some animals remains normal. We have compared nonproteinuric rats with those that developed HN in order to identify factors that influence susceptibility to immunologically medicated kidney disease. In the primary response to Fx1A, immunofluorescence tests showed that antibrush border titers in serum and immunoglobulin deposition in vivo were similar in all rats. However, complement was detected only in rats with proteinuria. Reimmunization with Fx1A at 30 weeks stimulated anamnestic antibody responses in all rats. Following reimmunization, 60% of nonproteinuric rats developed severe HN with an unusually rapid (1 week) onset. Once again, complement was present only in glomeruli of rats with proteinuria. It appears that titers of antibodies to brush border, measured by immunofluorescence tests, are not an index of the pathogenicity of the immune response to Fx1A. Immunological memory, leading to rapid expression of autoimmune disease upon reexposure to antigen, can be established by a primary immunization that does not produce clinical symptoms. Abnormal urine protein composition may provide a clue to subclinical immunopathology of the kidney.

Animals↗
PubMed1984

Immunopathogenesis of Heymann's nephritis.

Renal localization of the C5b-9 membrane attack complex (MAC) in relation to other complement components and immunoglobulins was studied at different stages of Heymann's nephritis and following reimmunization of Lew rats with stage IV disease. Trace amounts of the MAC were found during stages I and IV of disease, whereas during stages II to III, a period of active glomerular and tubular injury, moderate deposits of MAC were observed in glomeruli, periluminal cytoplasm of proximal tubular epithelial cells, and desquamated intraluminal brush border material. Following reimmunization of stage IV animals, a striking increase in the amount of MAC was observed. Moderate to marked deposition of IgG and C3 was also found during stages II and III at sites containing the MAC. Although a slight decrease in detectable IgG was noted during stage IV, a bright, confluent ribbon-like staining pattern was present in reimmunized animals. These data suggest that the MAC is a mediator for acute in situ immune-complex-induced glomerular and tubular cytoplasmic injury, although subsequent proteinuria may persist without continued complement pathway activation and assembly of the MAC.

Animals↗
PubMed1984

Transplacental transmission of antibodies to tubular basement membrane in guinea-pigs with autoimmune tubulointerstitial nephritis.

The offspring of female guinea-pigs with tubulo-interstitial nephritis were studied for possible passive transfer of disease. Whereas no immune deposits were seen on or before day 30 of gestation, IgG was detected in the tubular basement membrane (TBM) of fetuses at and after day 44. Serum of offspring contained antibodies to TBM, albeit in much lower titres than found in circulation of the mother guinea-pigs. No histopathological changes were seen in fetal kidneys. Thus, autoantibodies induced by heteroimmunization of pregnant guinea-pigs may be transmitted to offspring in the last third of the gestation period and can bind to fetal TBM. However, this transfer of antibodies does not cause disease.

Animals↗
PubMed1984

Passively transferred anti-brush border antibodies induce injury of proximal tubules in the absence of complement.

In active Heymann nephritis, antibodies directed against the brush border membrane of proximal tubules are able, when deposited in vivo, to cause substantial damage to the tubule epithelium. Prominent features of the lesion include fragmentation and loss of microvilli and proliferation of epithelial cells. Passive transfer of anti-brush border serum to appropriate proteinuric recipients also leads to proximal tubule pathology. In experiments reported here, full expression of the damage was observed in complement deficient recipients of passively transferred anti-brush border serum. A complement-independent process initiated by cross-linking of membrane determinants, which is analogous to the stimulation of B cell proliferation following cross-linking of Ig receptors by appropriate ligands, could account for the pathogenicity of anti-brush border serum.

Animals↗
PubMed1983

Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis.

The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral epithelium, and the TBM. Further experiments designed to selectively enhance or inhibit the deposition of MAC and assess consequent renal dysfunction are required to substantiate hypotheses concerning the in vivo membranolytic potential of the MAC in experimental immune complex glomerulonephritis.

Animals↗
PubMed1983

Relationship of kidney function to immunopathology in chronic serum sickness of rats.

This study sought to clarify the relationship between kidney function and immunopathology in chronic serum sickness (CSS) of rats. CSS was induced by chronic intravenous immunization with bovine serum albumin. Whole kidney function was studied during the course of CSS by assays of serum and urine. Single nephron function was evaluated by micropuncture techniques. Three categories (mild, moderate, severe) of kidney disease were identified from the analysis of kidney function in rats with CSS. Those categories represented distinct stages in the natural history of CSS nephritis. The three stages identified by measurements of function corresponded to distinct categories of kidney immunopathology. In rats with milk CSS, immune deposits were limited to the mesangium; histopathology was slight or absent. The only detectable change in protein handling was a small elevation of albumin concentration in tubule fluid. Abnormal proteinuria was a feature of moderate CSS; whole kidney glomerular filtration was not decreased despite evidence of significant immunopathology of glomeruli. Compromise of whole kidney function including decreased sodium excretion was only detected in the severe stage of CSS in association with diffuse proliferative glomerulonephritis. The transitions from mild to moderate and moderate to severe CSS were not gradual but occurred as discrete, sudden events.

Animals↗