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Biomedical subjects

G A Andres

Publications and source records attributed to G A Andres.

At least 37 records · Page 2Linked to original sources
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

Diagnostic immunopathology of the kidney biopsy in rheumatic diseases.

Nephropathies found in systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, and mixed connective tissue disease are discussed. Pathogenetic insights derived from the study of kidney tissue are highlighted and clinicopathologic correlations indicated. The question of whether to perform kidney biopsy in lupus patients is also addressed.

Animals↗
PubMed1983

Glomerular prostaglandin and thromboxane synthesis in rat nephrotoxic serum nephritis. Effects on renal hemodynamics.

Glomerular arachidonate cyclooxygenation by isolated rat glomeruli was assessed in vitro in antiglomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis by radioimmunoassay for prostaglandins (PG) and thromboxane. After a single intravenous injection of rabbit anti-rat GBM serum, we observed enhancement of glomerular thromboxane B2 (TxB2) synthesis as early as 2 to 3 h with smaller increments in PGF2 alpha, PGE2 and 6-keto-PGF1 alpha synthetic rates. On day 2 of the disease, the glomerular synthesis of TxB2 and, to a lesser extent, PGF2 alpha and PGE2 remained enhanced, whereas on days 8, 11, and 14, TxB2 was the only prostanoid synthesized at increased rates. Glomerular TxB2 synthesis correlated with the presacrifice 24-h protein excretion. 60 min after intravenous infusion of anti-GMB serum, glomerular filtration rate (GFR) decreased (0.66 +/- 0.04 to 0.44 +/- 0.03 ml/min per 100 g, P less than 0.05), without a significant change in renal plasma flow (RPF): 1.97 +/- 0.23 to 1.80 +/- 0.23 ml/min per 100 g) and without a change in glomerular PG synthetic rates. At 2 h, GFR and RPF reached a nadir (0.25 +/- 0.04 and 1.3 +/- 0.1 ml/min per 100 g, respectively) coinciding with a fivefold increment in glomerular TxB2. By 3 h GFR and RPF partially recovered to 0.43 +/- 0.07 and 1.77 +/- 0.20 ml/min per 100 g, respectively, P less than 0.05, despite further increments in TxB2 synthesis. This recovery of GFR and RPF coincided with increments in vasodilatory PG, (PGE2 and PGI2). The thromboxane synthetase inhibitor OKY-1581 markedly inhibited platelet and glomerular TxB2 synthesis and preserved GFR at 1, 2, and 3 h. Another thromboxane synthetase inhibitor, UK-38485, also completely inhibited platelet and glomerular TxB2 synthesis and prevented decrements of GFR at 2 and 3 h. A cyclooxygenase inhibitor, ibuprofen, inhibited platelet TxB2 and PGE2 synthesis and significantly reduced glomerular PGE2 but not TxB2 synthesis. In the ibuprofen-treated rats, the partial recoveries of GFR and RPF at 3 h were attenuated. The in vitro glomerular TxB2 synthesis correlated inversely with the presacrifice GFR and filtration fraction. These observations indicate that in anti-GBM nephritis there is enhanced synthesis of TxA2 and PG in the glomerulus that mediate changes in renal hemodynamics.

Animals↗
PubMed1982

Dissociation of immune complexes in tissue sections by excess of antigen.

Immune complexes (IC) present in the glomeruli of rabbits with chronic serum sickness (CSS) and in patients with systemic lupus erythematosus (SLE), idiopathic membranous nephropathy (IMN), and acute poststreptococcal glomerulonephritis (PSGN) were analyzed by incubation with antigenic preparations. The efficacy of these preparations to dissolve IC was assayed by comparison of results of direct immunofluorescence tests performed with the kidney tissues before and after incubation with antigenic preparations. The FITC-conjugated antisera used in these tests were specific for IgG, C3, and-in the case of CSS-for the eliciting antigen, bovine serum albumin (BSA). During the acute proteinuric phase of CSS in rabbits, incubation of tissue sections with BSA alone led to complete dissolution of IC. In many rabbits with late phase proteinuria, however, tissues had to be incubated with both BSA and aggregated fraction II of rabbit serum. In all biopsy specimens from patients with IMN, and in some specimens from patients with PSGN and SLE, aggregated fraction II of human serum resulted in complete or incomplete dissolution of IC. On the other hand, incubation of tissues with excess DNA in SLE or with streptococcal antigens PSGN did not lead to dissolution of IC. These studies suggest significant participation of antibodies to aggregated immunoglobulins (i.e., rheumatoid factors or rheumatoid-like factors) in IC found in the above-mentioned diseases. Other antigen -antibody systems, however, may also contribute to the deposits in the glomerulonephritides studied.

Animals↗
PubMed1982

Kidney complications.

Diabetic glomerulosclerosis in man and in all spontaneous-onset and chemically induced diabetes in experimental models is characterized by diffuse increase in mesangial matrix and glomerular basement membrane thickening. The most prominent features of the biochemical changes in the glomerular basement membrane are increase in the collagen-like components, decreased sialic acid, and increased glucosylation. However, the heterogeneity of the various glycoprotein components of the glomerular basement membrane and related components of the mesangium make comparative biochemistry difficult. Increased glomerular blood flow with no apparent alterations in the glomerular filtration coefficient in diabetes may be attributed to altered vascular control mechanisms which may include both hormonal mediation as well as changes in end-organ responsiveness. Although proteinuria is a common manifestation of diabetic involvement of the glomerulus, there is little biochemical or physiologic evidence as to the specific causes of increased glomerular filtration apparatus permeability. Further information as to the pathogenesis of diabetic vascular disease of the kidney and the ability to reverse pathologic changes by correction of the metabolic milieu will require analysis of carefully selected animal models. Particular care in experimental design must include the ability to integrate pathology, physiology, and biochemistry in each model in order to relate the information to human renal diabetic complications.

Animals↗
PubMed1982

Effect of reimmunization with Fx1A late in the course of Heymann nephritis.

There is evidence that active immunologic injury to glomeruli and tubules does not continue into a late stage of Heymann nephritis. Support for that view has been provided by the results of a study of kidney immunopathology following reimmunization with Fx1A late in the course of the disease. An increased derangement of kidney function, observed after reimmunization, was related to changes detected in kidney morphology. The observation that immunologically mediated injury in Heymann nephritis may occur only during a limited period could have implications for our understanding of the pathogenesis of human membranous nephropathy.

Animals↗
PubMed1982

In vitro alternative pathway activation of complement by the brush border of proximal tubules of normal rat kidney.

The purpose of this study was to investigate which structures of the nephron, if any, are capable of directly activating the complement (C) system. To this end, two sets of experiments were performed. First, activation of C was assessed on sections of frozen kidney tissue, using the indirect immunofluorescence technique for the demonstration of C fixation. Second, glomerular or tubular fractions of kidney were incubated with normal fresh serum, and subsequent C consumption was measured. The data obtained support the interpretation that the brush border of proximal tubules activates the alternative pathway of the C system. This phenomenon may have pathogenic significance in conditions of aselective proteinuria.

Anaphylatoxins↗
PubMed1981

Lack of evidence for a role of renal tubular antigen in human membranous glomerulonephritis.

Renal tissue from 71 patients with membranous glomerulonephritis was studied for the presence of renal tubular antigens in glomerular deposits by indirect immunofluorescence, using a rabbit antiserum prepared against a human renal tubular antigen, Fx1A. The rabbit antiserum was reactive with antigens normally present in the brush border regions of proximal tubules of human and rat kidneys and in the glomerular deposits of rats with Heymann nephritis. However, renal tubular antigens were not detectable in any of the cases of human membranous glomerulonephritis, either before or after partial elution of immunoglobulins from glomeruli. Eluates of renal tissue from 5 of the patients and sera from 6 patients did not contain antibodies against renal tubular antigens demonstrable by immunofluorescence. These findings fail to provide evidence for a role of renal tubular antigens in human membranous glomerulonephritis.

Adolescent↗
PubMed1981

Experimental anti-alveolar basement membrane antibody-mediated pneumonitis. I. The role of increased permeability of the alveolar capillary wall induced by oxygen.

Attempts to produce in animals lung lesions mediated by anti-alveolar basement membrane (ABM) antibodies have thus far been inconclusive. The aim of the present study was to test the hypothesis that increased permeability of the endothelial cell lining is needed before circulating antibodies can gain access and bind to ABM. A goat antiserum was prepared against purified rabbit ABM. After i.v. injection of the gamma-globulin fraction into rabbits, goat IgG was detected in glomerular basement membrane but not in ABM. However, 17 of 19 rabbits injected with anti-ABM antibody after exposure for 62 to 66 hr to 100% oxygen had a diffuse linear binding of goat IgG in ABM and died with pulmonary edema and hemorrhagic pneumonitis. By the paired label isotope technique, uptake of anti-ABM antibodies in lung far exceeded that in kidney. Semiquantitative histologic studies indicated that the lesions in the lung of these rabbits were more severe then those found in rabbits exposed to 100% oxygen and injected with normal goat serum gamma-globulin. None of the latter animals died with pulmonary edema; none was found to have binding of goat IgG in the lung. The results indicate that under normal physiologic conditions the endothelium is a barrier that prevents binding of IgG antibodies to ABM. The increased permeability induced by oxygen in the alveolar capillary wall is a nonimmunologic factor allowing the development of a reproducible model of severe anti-ABM antibody-mediated pneumonitis.

Animals↗