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Biomedical subjects

W A Border

Publications and source records attributed to W A Border.

At least 91 records · Page 5Linked to original sources
PubMed1984

In situ formation of subepithelial immune complexes in the rabbit glomerulus: requirement of a cationic antigen.

In a previous study we examined the role of antigenic electrical charge as a factor influencing glomerular immune complex (IC) localization in the rabbit. From that study patterned after chronic serum sickness nephritis it was demonstrated that the administration of charge-modified cationic bovine serum albumin (BSA) of isoelectric point (pI) greater than or equal to 9.5 invariably resulted in heavy subepithelial deposits, whereas native BSA (anionic, pI 4.5) produced principally mesangial deposits. In order to investigate the mechanism by which the immune deposits formed, passive serum sickness was induced in New Zealand white rabbits by unilaterally perfusing kidneys of nonimmunized rabbits with five alternating cycles of saline, antigen and antibody, or immunized rabbits with saline and antigen alone. Localization of BSA and IgG along the glomerular basement membrane (GBM) occurred only after exposure to cationic BSA and antibody; nonimmunized animals perfused with cationic BSA and antibody to cationic BSA uniformly developed generalized, diffuse nearly linear deposits of IgG and BSA along the GBM. Similar deposits, which became progressively more granular after exposure to circulating antibody, were seen after the perfusion of cationic BSA alone into animals actively immunized with cationic or native BSA. Ultrastructural examination showed effacement of foot processes and isolated, irregular subepithelial and subendothelial deposits. Control perfusion employing alternating cycles of native BSA and anti-native BSA antibody, cationic BSA and normal sheep IgG, or native BSA alone in animals actively immunized with native or cationic BSA failed to develop glomerular IgG deposits. All control kidneys were normal on ultrastructural examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Interstitial Tamm-Horsfall protein in rejecting renal allografts. Identification and morphologic pattern of injury.

In a study of renal allografts with acute rejection primarily or exclusively of the cellular type, extratubular Tamm-Horsfall protein was identified in 63.6% of the specimens, representing 76.1% of the patients whose tissues were examined. There was no evidence of extrarenal obstruction in any patient. This high incidence has not been previously reported. A pattern of development of this phenomenon was determined using combined light and electron microscopies and specific anti-Tamm-Horsfall antiserum. Interstitial lymphocytes and monocytes infiltrated into the walls of tubules causing disruptions of basement membranes, thereby creating free communications between lumina and interstitium. In distal tubules with casts, the matrices extended into the interstitium where they were admixed with leukocytes and few erythrocytes. In a small number of specimens, polyps of Tamm-Horsfall protein were identified in veins or interstitial capillaries. Extratubular Tamm-Horsfall protein was not associated with diminished graft survival. These findings delineate, in detail, one of several mechanisms of escape of Tamm-Horsfall protein from tubules into the interstitium; they may be applicable for the genesis of this abnormality in other forms of acute interstitial nephritis.

Biopsy, Needle↗
PubMed1983

Role of immunoglobulin class in mediation of experimental mesangial glomerulonephritis.

The contribution of immunoglobulin class to the histology and ultrastructure of renal lesions were examined in an experimental model of glomerulonephritis in which the glomerular deposits were selected to be predominantly IgM or IgG. The selection was accomplished by immunizing and then injecting rabbits with a carrier preparation plus heat-denatured (HD) DNA (n = 11) or ultraviolet-irradiated (uv) DNA [n = 11). It has been shown previously that HD DNA gives rise to an IgM antibody response and uv DNA to an IgG response. Groups of rabbits immunized with each preparation produced largely IgM (HD DNA) or IgG (uv DNA) anti-DNA antibody. After 10 and 20 weeks of injections, animals receiving both antigens developed diffuse mesangial hypercellularity with either IgM or IgG deposits accompanied by C3; by ultrastructural analysis all deposits were confined to the mesangium. By 28 weeks, heavy mesangial IgM and IgG deposits were noted but no quantitative or qualitative differences in the renal histology was observed. Individual animals developed sporadic hematuria and azotemia but proteinuria was not found. These results show that both IgM and IgG can mediate experimental mesangial proliferative glomerulonephritis and that the immunoglobulin class of the glomerular deposits does not influence the appearance of the renal lesion.

Animals↗
PubMed1983

Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit.

Intravenous cationic bovine serum albumin (BSA, pI > 9.5) induces membranous nephropathy in immunized rabbits. In this study, unimmunized rabbits received intravenous injections of cationic (n = 3) or native (n = 3) or native (n = 3) BSA, followed by ex vivo isolated left renal perfusions with sheep anti-BSA antibody. Capillary wall deposits of IgG and C3 were seen exclusively in the group receiving cationic BSA, confirming an in situ pathogenesis for cationic, BSA-induced membranous nephropathy, and demonstrating the importance of a cationic antigen for its production. We then explored whether membranous nephropathy in this model is prevented by the concomitant injection of protamine sulfate, a filterable, relatively non-immunogenic polycation. An in vitro study demonstrated that protamine sulfate incubated with glomerular basement membrane (GBM) decreased the subsequent binding of radiolabeled cationic BSA (P < 0.05). In vivo, protamine sulfate was shown to bind to anionic sites in the glomerular capillary wall after intravenous injection.Groups of rabbits received 3 wk of daily intravenous injections of cationic BSA alone (n = 15) or cationic BSA and protamine (n = 18). After 2 wk of injection of cationic BSA alone, typical membranous nephropathy developed. Granular deposits of IgG and C3 were present along the GBM associated with subepithelial dense deposits, foot process effacement, and marked albuminuria. Protamine significantly reduced or prevented the formation of deposits (P < 0.001) and in6 of 18 protamine-treated animals, existing deposits decreased or disappeared between 2 and 3 wk of injection. Albuminuria was significantly reduced in protamine-treated animals with a mean of 124+/-55 mg/24 h compared to 632+/-150 mg/24 h in the control group receiving cationic BSA alone. No significant differences between the groups were noted in serum lev9lsof IgG, C3, anti-BSA antibody, or circulating immune complex size. Studies in additional animals (n = 5) given radiolabeled cationic BSA showed that protamine did not alter the clearance of cationic BSA from serum. Control experiments showed that protamine's beneficial effects were not related to its weak anticoagulant property or toits theoretical ability to deplete tissue histamine. The administration of heparin (n = 6) or diphenhydramine (n = 6) had no effect on the development of the epimembranous lesion compared to the group receiving cationic BSA alone. In addition, homogenized whole kidney histamine content was not significantly different in the group receiving cationic BSA alone compared to the group receiving cationic BSA and protamine. This work shows that a cationic BSA-induced glomerular lesion can be produced by a renal perfusion technique involving in situ complex formation and that this process requires a cationic antigen for its development. We believe that the demonstrated beneficial effects of protamine are due to its ability to bind to glomerular anionic sites, and that this electrostatic interaction results in inhibition for the further binding of the cationic antigen, thereby limiting the severity of glomerulonephritis in this model.

Animals↗
PubMed1983

Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis.

We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group.

Adult↗
PubMed1982

Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen.

We examined the role of antigenic electrical charge as a determinant of glomerular immune complex localization in the rabbit. Serum sickness nephritis was induced in groups of New Zealand white rabbits by daily 25-mg intravenous injections of bovine serum albumin (BSA) chemically modified to be cationic (pI > 9.5) or more anionic (pI, 3.5-4.6); an additional group received unmodified native BSA (pI, 4.5-5.1). Factors known to influence immune complex localization, e.g., molecular size of the administered antigen and resulting circulating immune complexes, immunogenicity, and disappearance time from the circulation were examined and found to be similar for both anionic and cationic BSA. Charge modification did increase the nonimmune clearance of cationic and anionic BSA compared with native BSA. Injected cationic BSA was shown in paired label experiments to bind directly to glomeruli compared with native BSA. The renal lesion produced by cationic BSA was markedly different from that found in rabbits given anionic or native BSA. Animals receiving cationic BSA uniformly developed generalized diffuse granular capillary wall deposits of IgG, C3, and BSA detected after 2 wk of injections and increasing until death at 6 wk. Qualitatively similar deposits were produced by the administration of low doses of cationic BSA of only 1 or 10 mg/d. In contrast, the injection of both anionic and native BSA resulted in mesangial deposits at 2 and 4 wk with capillary wall deposits appearing by 6 wk. Ultrastructural examination of animals receiving cationic BSA revealed pure, extensive formation of dense deposits along the lamina rara externa of the glomerular basement membrane whereas such deposits were absent or rare in animals injected with the anionic or native BSA. Albuminuria was significantly greater at 6 wk in the groups receiving cationic BSA with a mean of 280 mg/24 h compared with 53 mg/24 h in the combined groups injected with anionic or native BSA. Blood urea nitrogen values were similar in all groups at 2 and 4 wk but higher in the animals receiving cationic BSA at 6 wk. These experiments describe the reproducible induction of epimembranous immune deposits by administration of an exogenous cationic antigen. They suggest that antigenic charge can play an important role in the pathogenesis of membranous nephropathy by permitting direct glomerular binding of an antigen and predisposing to in situ immune complex formation.

Albuminuria↗
PubMed1982

Henoch-Schönlein purpura: simultaneous demonstration of IgA deposits in involved skin, intestine, and kidney.

Recent reports indicate that circulating IgA immune complexes may play a primary role in the pathogenesis of Henoch-Schönlein vasculitis and are responsible for the granular deposits of IgA seen in biopsy specimens of skin and kidney. A patient had classic Henoch Schönlein syndrome, including hematuria, purpura, and abdominal pain; tissue taken simultaneously from the small intestine, skin, and kidney was examined by light immunofluorescent, and electron microscopy. Granular deposits of IgA were found in small-vessel walls of the intestinal tissue and skin, and in the glomerular mesangium. This provides further support for the notion that IgA deposits produce tissue injury in intestine, skin, and kidney in Henoch-Schönlein syndrome.

Adult↗
PubMed1981

Crescentic glomerulonephritis: immune vs. nonimmune mechanisms.

An immunopathological study of renal biopsies from 38 patients with glomerulonephritis with greater than 30% crescents was performed. All had evidence of immune deposits in glomeruli: 9 were characterized by linear fluorescence staining (antiglomerular basement membrane antibodies) and 29 had granular capillary wall and/or mesangial deposits. In the former group, 3 (33%) had associated pulmonary hemorrhage. In the latter group, the glomerular lesions in 18 (62%) were part of well-defined systemic illnesses, whereas in the remainder, the abnormalities were apparently limited to the kidney. The prognosis was uniformly grave, for all patients with adequate follow-up developed end-stage renal failure or died. In contrast to other reports of crescentic glomerulonephritis, we could not document the existence of an 'immunofluorescence negative' form of crescentic glomerulonephritis.

Adolescent↗
PubMed1981

Cell elastimetry in the detection of antineutrophil antibodies.

Cell elastimetry has been applied to the measurement of antineutrophil antibodies. This technique measures, under direct visualization, the negative pressure required of aspirate PMNs into small-pored pipettes. Two groups of studies were carried out: (A) In the first group of studies, normal PMNs were incubated with 1 of 8 known antineutrophil serums. Each serum significantly decreased membrane deformability--i.e., cells became more rigid. The study was conducted in an entirely blind fashion. Randomly coded serums from patients and controls were studied for deformability by observers unaware of the code. (B) In the second group of studies, sera containing immune complexes were incubated with normal PMNs. No significant effects were noted upon deformability. As a single cell assay that partially reflects membrane rigidity, elastimetry may, therefore, have potential in the further characterization of mechanisms by which such antineutrophil antibodies compromise neutrophil functions.

Adult↗
PubMed1980

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus.

Serial serum samples from 48 patients with systemic lupus erythematosus (SLE) were assayed for C3, anti-DNA antibody, and circulating immune complexes (CIC). CIC were measured by the fluid phase (FClq) and solid phase (SClq) Clq binding assays. Elevations of the SClq results were associated with the presence of manifestations of SLE (P less than 0.001), including active renal disease (P less than 0.005) and arthritis (P less than 0.001), as well as changes in degree of disease activity which prompted physician action. A change in the SClq results correctly predicted a change in disease activity 82% of the time (P less than 0.005). Abnormalities of FClq, anti-DNA antibody, and C3 were neither associated with nor predictive of changes in disease activity of SLE. These data suggest that the SClq method of determining CIC is the most reliable laboratory indicator of clinical activity in SLE.

Adolescent↗
PubMed1980

Renal biopsy diagnosis of clinically silent multiple myeloma.

Acute renal failure due to multiple myeloma is uncommon but may be the presenting feature of the disease. When it occurs, the underlying multiple myeloma is usually easily diagnosed by the presence of a serum M protein, hypercalcemia, skeletal pain, or typical bone lesions. We report here four cases of patients who, at the time they developed acute renal failure, had none of these findings nor any other historical or physical evidence of multiple myeloma. A renal biopsy in all four cases revealed the typical diagnostic features of "myeloma kidney" and led to confirmation of the diagnosis by bone marrow examination. Tamm-Horsfall protein was identified within myeloma casts and the glomerular urinary space, suggesting that tubular obstruction and retrograde urine flow precedes the development of "myeloma kidney" and acute renal failure.

Acute Kidney Injury↗
PubMed1980

Circulating immune complexes in rats with autologous immune complex nephritis.

Autologous immune complex nephritis (Heymann nephritis) was actively induced in rats by immunization with high (10 mg.) and low (1 mg.) doses of renal tubular epithelial antigen in complete Freund's adjuvant. The development of proteinuria and granular capillary wall deposition of IgG confirmed the previously well described membranous nephropathy which characterizes this experimental disease. Circulating immune complexes were demonstrated by both the fluid phase and solid phase C1q binding assays in both high and low dose experimental groups. The prevalence of such immune complexes was significantly greater in the experimental than in the control groups immunized with adjuvant alone or liver homogenate in adjuvant. The circulating immune complexes bound to C1q were 16 to 23 S in size and were proven to contain a renal tubular antigen. These data, in combination with the previous demonstration of renal tubular antigen and its antibody in kidneys from rats with autologous immune complex nephritis, are consistent with a circulating immune complex pathogenesis of this model of the actively induced autologous immune complex nephritis in rats.

Animals↗
PubMed1980

Non-specificity of circulating immune complexes in patients with acute and chronic liver disease.

Circulating immune complexes have been described in viral hepatitis and primary biliary cirrhosis but their significance is unclear. Seventy-three patients with acute and chronic liver diseases were evaluated to determine the specificity of immune complex detection for a given liver disease. Immune complexes were measured by the fluid- and solid-phase Clq-binding assays. They were demonstrated frequently in all patients with liver disease, including those with viral hepatitis, alcoholic cirrhosis, chronic active and persistent hepatitis, drug-induced hepatitis and hepatic metastases. The presence of immune complexes was not specific for a given type of liver disease and did not correlate with hepatic dysfunction. We conclude that the detection of immune complexes is of no apparent diagnostic use in liver disease. Further evaluation of the antigen-antibody composition would be required to determine any pathogenic significance of the detected circulating immune complexes.

Acute Disease↗