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Biomedical subjects

G A Andres

Publications and source records attributed to G A Andres.

At least 19 recordsLinked to original sources
PubMed1990

Characterization of a tubular basement membrane component reactive with autoantibodies associated with tubulointerstitial nephritis.

A kidney tubular basement membrane (TBM) component that is bound by antibodies from individuals with anti-TBM antibody-associated tubulointerstitial nephritis (TIN) was purified and characterized (TIN antigen). TIN antigen was prepared from rabbit TBM by extraction with guanidine and purified by ion-exchange, gel filtration, and reversed-phase chromatography. Based upon yields of protein and antibody reactivity, TIN antigen accounts for about 9% of the mass of TBM and thus is a major component of this basement membrane. A predominant 58-kDa form comprises about 90% of purified TIN antigen, and a 50-kDa form accounts for the remainder. The two forms share the amino-terminal sequence Ser-Ile-Phe-Gln-Gly-Gln-Tyr-X-Arg-Ser-Phe-Gly- and give similar tryptic peptide maps, indicating that they are structurally related. Their amino acid compositions overall are similar to laminin and entactin/nidogen. The absence of hydroxyproline and hydroxylysine and the low levels of glycine in TIN antigen indicate that it is noncollagenous. No similarities were found between other known proteins and sequences of tryptic peptides and the amino terminus of TIN antigen, suggesting that it is distinct from other characterized basement membrane components. A goat polyclonal antibody toward rabbit TIN antigen showed the same kidney distribution as human antibodies and was completely inhibited in enzyme-linked immunosorbent assay by purified TIN antigen. These data further support the idea that TIN antigen is the primary target for anti-TBM antibodies associated with TIN. This research presents methods to prepare TIN antigen for biochemical studies and investigations of its role in anti-TBM autoimmune TIN.

Amino Acid Sequence↗
PubMed1979

Experimental chronic serum sickness in rats. A model of immune complex glomerulonephritis and systemic immune complex deposition.

This article describes a method of immunization that produces chronic serum sickness in rats within a relatively short time. Fisher rats, which were immunized subcutaneously three times with bovine serum albumin (BSA) in adjuvant, responded with high titers of antibodies to BSA. 2 weeks after the third subcutaneous immunization, daily increasing amounts of BSA were injected either intraperitoneally or intravenously. When an intravenous dose of 2mg of BSA was reached, the rats were given daily intravenous injections of BSA for several weeks. This procedure, which avoided death from anaphylaxis, induced severe proliferative glomerulonephritis in all the rats and produced deposition of antigen-antibody complexes in many other organs besides the kidney. This highly reproducible model of experimental chronic serum sickness in inbred animals may have applications for the study of the mechanisms of immune complex disease.

Animals↗
PubMed1979

Structural observations on epithelioid and giant cells in experimental autoimmune tubulointerstitial nephritis in guinea pigs.

In order to analyze the role of phagocytic cells in experimental antitubular basement membrane (TBM) antibody-mediated nephritis, Hartley guinea pigs (GP) were immunized with rabbit tubular basement membrane (TBM) in complete Freund's adjuvant and pertussis vaccine. Renal tissue was obtained 10 to 15, 15 to 25, and 25 to 35 days after the start of immunization. Severe renal tubulointerstitial (RTI) nephritis developed in 95% of the animals. Linear deposits of IgG and C3 along TBM were seen 10 days after initial immunization. A few days later, monocytes and macrophages infiltrated the interstitium and subsequently differentiated into epithelioid and foreign body-type giant cells (GC). The GC were most actively involved in the destruction of the TBM: Cytoplasmic pseudopodia of the GC adhered to the TBM; the areas of membrane apposition were several microns in length; no evidence of specialization was found in the plasma membrane adjoining the TBM; no cellular organelles, except for abundant microfilaments, were seen in the contact regions. The initial contact was followed by lysis of plasma membrane of the GC and TBM, perforation of TBM, and phagocytosis of TBM fragments. Concomitantly, fluorescent staining for IgG along the TBM became discontinuous or disappeared. Destruction of TBM was accompanied by degeneration of tubular epithelial cells and collapse of tubular architecture. The morphologic observations are consistent with the hypothesis that, in GP, autoimmune RTI nephritis damage of TBM results from the cooperation of humoral and cellular mechanisms, probably akin to those of antibody-mediated lymphocytotoxicity.

Animals↗
PubMed1978

Deposition of circulating antigen--antibody complexes in the gastrointestinal tract of rabbits with chronic serum sickness.

The possible role of circulating immune complexes (IC) in the production gastrointestinal lesions was studied in rabbits with chronic serum sickness (CSS) induced by multiple daily injections of bovine serum albumin (BSA). All rabbits generating a marked antibody response developed IC glomerulonephritis. In approximately 50% of these rabbits granular deposits of BSA, rabbit IgG, and C3 were also found in the gastrointestinal tract. The immune deposits in the gastrointestinal tract were mainly present in the vessel walls, close to the intestinal glands and the surface epithelium, and between the smooth muscle cells. This was accompanied by slight to moderate edema of the mucosa and the submucosa and mild infiltration of inflammatory cells. Electron-densedeposits were found in a pattern corresponding to that observed for BSA, rabbit IgG, and C3. Degranulated neutrophils, basophils, and mast cells were noticed in the interstitium. The presence in the same areas of granular deposits of BSA, IgG, and C3, corresponding to electron-dense deposits, suggests that the deposits contain BSA-anti-BSA complexes. These findings show that in rabbits with CSS circulating IC may localize and induce injury in the gastrointestinal tract.

Animals↗
PubMed1978

The morphologic basis of proteinuria in experimental chronic serum sickness glomerulonephritis. A light and electron microscopic study using horseradish peroxidase and ferritin as tracers.

The morphologic basis of proteinuria in experimental chronic serum sickness glomerulonephritis in rabbits was studied by light and electron microscopy using horseradish peroxidase (effective radius 30 A; mol. wt. 40,000) and ferritin (effective radius 60 A; mol. wt. 480,000) as protein tracers. It was found that more ferritin, but paradoxically, less horseradish peroxidase gained access to the urinary space. Observations made by electron microscopy appeared to indicate a decreased permeability of most part of the damaged glomerular capillary wall to both tracers. These results favor the interpretation that proteinuria in chronic serum sickness glomerulonephritis is the result of focal rather than diffuse increase in permeability of the glomerular capillary wall. Lesions of segments of the nephron other than the glomerular capillary wall, may contribute to the leakage of proteins to the urinary space.

Animals↗
PubMed1977

The endothelial damage of pulsatile renal preservation and its relationship to perfusion pressure and colloid osmotic pressure.

To evaluate the effects of pulsatile preservation, 34 heterotopic renal autografts with immediate contralateral nephrectomy were divided into four groups with either the pulsatile preservation or cold storage technique. Group I had pulsatile preservation with plasma-albumin perfusate at a mean pressure of 60 mm. Hg and a colloid osmotic pressure (COP) of 20 to 50 cm. H2O. Group II had pusatile preservation with the same plasma-albumin perfusates as in Group I, but at a mean pressure of 30 mm. Hg. Group III had pulsatile preservation with albumin-phosphate buffer solution at a mean pressure of 30 mm. Hg. Group IV used cold storage technique. Group I demonstrated severe endothelial destruction and denuding of basement membrane. The changes were inversely related to COP. None of these kidneys functioned and, following transplantation, had persistent severe tubular damage and plugging of glomerular capillary loops with platelets, fibrinogen, and white cells. In Groups II and III, there were minimal changes, consisting of widening of the endothelial pores and focal endothelial damage. All of these kidneys functioned following reimplantation with minimal ultrastructural alterations. Group IV had no glomerular changes following preservation or following transplantation. All preservation techniques produced proximal tubular damage. There is a definite mechanical lesion associated with pulsatile preservation, which can be minimized by utilizing low perfusion pressures and solutions of high colloid osmotic pressure and which has the potential of producing a picture resembling hyperacute rejection following transplantation.

Animals↗
PubMed1976

Immune complex orchitis in vasectomized rabbits.

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen-antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness.

Animals↗
PubMed1976

A ubiquitous tissue antigen and its corresponding antibody in sera of patients with glomerulonephritides.

Sera and 5% PEG-precipitates from 20 patients with IMN, 18 with MPGN, 20 with SLE, 8 with anti-GBM disease and 17 with other varieties of glomerulonephritides, 19 patients with chronic liver or intestinal diseases, as well as those from 40 healthy adults, were tested by gel prcipitation for the presence of a ubiquitous tissue antigen (UTA) and/or its corresponding antibody, previously shown to be associated with renal disorders. The antigen was detected in sera of 5 patients with IMN, one with anit-GBM disease and one with SLE. Corresponding antibodies were present in sera of 2 patients with IMN. In 4 of 5 patients with IMN and UTA was only detected if the sera were first treated with PEG (mol. wt. 6,000) which induces precipitation of antigen-antibody complexes and other high molecular weight components in serum. The UTA was not detected in renal glomeruli by immunofluorescence. The possible significance of these findings in the pathogenesis of renal diseases is discussed.

Antibodies↗
PubMed1976

Immune deposit nephritis in infectious mononucleosis.

A 22-year-old white male (L.V.) died of gram-negative septicemia complicating infectious mononucleosis (IM) that was associated with jaundice and oliguric renal failure. The kidney showed mesangial granular deposits of IgM and C3, mesangial electrondense deposits, and interstitial infiltrates of infiltrates of mononuclear cells, including atypical lymphocytes. Eluates obtained from kidney, spleen and liver contained Paul--Bunnell (PB) antibodies. Presence of PB antigens in these tissues was indicated by absorption of PB antibodies from IM sera, with the sediments resulting from tissue elutions. The IgM mesangial deposits were partially eluted with acid buffer at 56 degrees C and then reconstituted by incubation with IM sera or with immunoglobulins eluted from tissues of patient L.V. The presence in renal structures of PB antigens, IgM heterophile antibody, C3 and electron-dense deposits is consistent with the hypothesis that heterophile immune complexes were localized in the kidney and that they contribute in the pathogenisis of IM nephritis.

Adult↗
PubMed1976

Antigen in immune complex nephritis. V. Recovery and identification by gel precipitation.

A procedure is described for detection of antibodies and antigens in 'immune complex' nephritis. Kidney tissue is minced, washed and sealed in a well of an agarose or agar plate. Separation of immune complexes is achieved by electrophoresis at 56 degrees. Afterwards, antibody is readily detected in reaction with a proper anti-IgG serum. Antigen is identified by its corresponding antibody, the reaction with which is, in some instances, strengthened by counterimmunoelectrophoresis.

Adult↗
PubMed1975

Membranoproliferative glomerulonephritis with polyarteritis: a case report.

A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes.

Age Factors↗
PubMed1975

Interstitial immune complex nephritis in patients with systemic lupus erythematosus.

Interstitial immune complex nephritis in patients with systemic lupus erythematosus (SLE). Renal tissues from 45 patients with SLE nephritis, 34 patients with idiopathic membranous nephropathy (IMN) and 77 patients with minimal glomerular disease (MGD) were studied by light, immunofluorescence and electron microscopy. Interstitial nephritis characterized by focal or diffuse infiltration of inflammatory cells, tubular damage and interstitial fibrosis was observed in 66% of SLE patients. Fluorescein-conjugated antibodies to immunoglobulins or complement or both were bound to peritubular capillaries, interstitium and tubular basement membranes (TBM) in 53% of patients with a granular pattern corresponding to opaque deposits seen by light or electron microscopy or both. Antibodies reactive with thymidine or cytosine or both were bound to interstitial structures in 19% of patients tested and showed the same granular distribution. Interstitial cellular infiltration was rare and deposits of immunoglobulins and complement were rare or absent in IMN and MGD, whereas deposits of DNA products were never observed. The findings are consistent with the interpretation that in patients with SLE nephritis immune deposits, presumably containing DNA-anti-DNA complexes, localize in peritublular capillaries, TBM and interstitum, thereby producing an inflammatory reaction which contributes to development and evolution of renal diseases.

Antibodies↗