PubMed Health⌕ Search

Biomedical subjects

A C Dash

Publications and source records attributed to A C Dash.

12 recordsLinked to original sources

Passive immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta protects from LPS enhancing glomerular injury in nephrotoxic nephritis in rats.

Glomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/- 3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/- 6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1 beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19, anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24 h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha.

Animals↗

Exaggerated glomerular albuminuria after cobra venom factor in anti-glomerular basement membrane disease.

The mechanisms by which intercurrent bacterial infections are associated with increased tissue injury in some forms of glomerulonephritis may include complement activation by bacteria and subsequent increased glomerular neutrophil (PMN) infiltration. We have studied the effect of complement activation after cobra venom factor (CVF) in anti-glomerular basement membrane (GBM) antibody-mediated disease. A single injection of CVF 24 h before the administration of heterologous nephrotoxic globulin (NTG) to Sprague-Dawley rats resulted in greatly increased albuminuria in some animals on the second day of this model. This phenomenon was reproducible and depended on the presence of circulating PMN and complement. We have previously shown that the administration of CVF on days 9 and 11 of the HgCl2 model in inbred Brown Norway rats, resulted in increased albuminuria in all animals at day 17 (p less than 0.05). The administration of small amounts of CVF with consequent complement activation in antibody-mediated disease represents a model for the increased injury seen after infection in human disease.

Albuminuria↗

The effect of a protein meal on three fluid-phase assays for circulating immune complexes.

Serial blood samples were taken from eight patients with systemic lupus erythematosus and five normal controls before and after a standard meal containing 20 g of protein. The samples were assayed for circulating immune complexes by the fluid-phase C1q, monoclonal rheumatoid factor and conglutinin-binding assays. No significant differences were seen in the post- as compared to the pre-prandial levels of circulating immune complexes. In neither controls nor patients did circulating complexes appear for the first time within 90 min after starting the meal. We conclude that if systemic antigen--antibody reactions occur soon after a protein meal they are not detected by the polyethylene glycol-dependent tests in current use and do not appear to influence the immediate clearance of endogenous immune complexes.

Antigen-Antibody Complex↗

Comparative clinical study of protein SAP (amyloid P component) and C-reactive protein in serum.

The serum concentration of protein SAP (amyloid P component) has been measured for the first time in a substantial series of normal individuals and patients with various diseases, and the results contrasted with the levels of the related protein C-reactive protein (CRP). The mean +/- s.d. concentration of protein SAP was 43 +/- 14 microgram/ml in seventy-six normal men, 33 +/- 10 microgram/ml in eighty-six normal women and 4 +/- 2 microgram/ml in thirty-six normal cord sera. Unlike CRP, whick is a major acute phase reactant, protein SAP was only slightly elevated in inflammatory and neoplastic diseases in which CRP was greatly increased. The level of protein SAP was significantly depressed in patients with hepatic disease, suggesting that its measurement might be of value in their management.

Amyloid↗

Isolation and study of murine C3.

C3 was isolated in purified form from fresh murine serum and plasma by precipitation as euglobulin followed by removal of other proteins on immunoadsorbent columns bearing antibodies raised against specifically C3 depleted serum. Recovery was 30--55% and the C3 was all in its native form. Functional activity was demonstrated by fixation of the C3 on EAC142gp cells and by interaction with lymphocyte C3 receptors. Mouse C3 in plasma and after isolation had a molecular weight of 240,000. Its cleavage by classical pathway and cobra factor induced C3 convertases and by trypsin yielded a major conversion product with molecular weight not less than 210,000, the electrophoretic mobility of which differed when it was generated from isolated C3 rather than in plasma.

Animals↗

Enumeration of immunoglobulin-bearing lymphocytes in whole peripheral blood.

A new method is described for the detection by immunofluorescence of lymphocyte populations in whole peripheral blood. Lymphocytes are identified by their lack of intracellular peroxidase, and the absolute number of different populations can be accurately enumerated by avoiding procedures for isolating mononuclear cells before fluorescent staining. Among twenty-two normal individuals the mean +/- s.d. percentage and absolute number of lymphocytes with stable surface immunoglobulin were as follows: IgM, 8-1+/-2-3%, 142+/-60/mu1; IgD,8-9+/-2-2%, 212+/-85/mu1;IgA, 2-2+/-1-0%, 41+/-24/mu1; IgG, 2-3+/-1-6%, 60+/-47/mu1. It was confirmed that the detection of true IgG-bearing lymphocytes depends on washing the blood at 37degrees before staining or the use of F(ab)2 anti-IgG antibodies. The proportion of lymphocytes stained by whole IgG polyvalent anti-immunoglobulin antibody, which detects both true immunoglobulin-bearing lymphocytes (B cells) and Fc receptor cells was constant (20-5+/-1-0%) both in and between individuals, but the absolute numbers (380+/-117/mu1) varied with the lymphocyte count.

Adult↗

Immunological studies in inflammatory bowel disease.

Three aspects of immunological function were studied in patients with Crohn's disease and ulcerative colitis (inflammatory bowel disease): atopic status and serum IgE levels; serum concentration of C-reactive protein; and C3 activation. The incidence of atopy, assessed by prick testing with common allergens, did not differ in patients with inflammatory bowel disease from healthy controls. 12 of 39 patients with Crohn's disease and 5 of 20 with ulcerative colitis, among whom were some non-atopic subjects, had elevated serum levels of IgE. Serum levels of C-reactive protein in patients were significantly greater than normal, even in those in whom the disease was clinically quiescent. Symptomatic patients with Crohn's disease had significantly higher levels than similar patients with ulcerative colitis and in Crohn's disease the levels correlated well with an overall assessment of severity and disease activity. Although conversion of C3 was detected in fresh serum samples from inflammatory bowel disease patients and not controls, only minimal traces were present in just 7 of 89 samples of EDTA--plasma from 47 patients; this finding did not correlate with disease activity. However, there were low titres of immunoconglutinin in the sera of some patients, but not in controls, suggesting that complement activation may be occurring in vivo.

C-Reactive Protein↗