Biomedical subjects

E Brouwer

Publications and source records attributed to E Brouwer.

At least 55 records · Page 3Linked to original sources

PubMed1994

Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis.

We examined immunopathological changes of podocytes in vivo which, based on in vitro studies, are thought to be relevant for the pathogenesis of renal diseases. We investigated the alterations of podocytes in local inflammation in a recently developed model of pauci-immune necrotizing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plastic embedded kidney sections at different time points of the disease were incubated with antibodies directed to MHC class I, MHC class II, ICAM-1 and to relevant cytokines. Strong glomerular expression of MHC class I, II and ICAM-1 was found within 4 days, and plastic embedded sections clearly demonstrated increased cell membrane staining of podocytes. Increased glomerular interferon-gamma (IFN-gamma) was detected within 24 h of induction of NCGN, and IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) were found from day 4. The potency of these cytokines to induce adhesion molecules on podocytes was investigated on rat glomerular epithelial cells in vitro. By using FACS analysis and electron microscopical techniques, we found that the in vivo expression of MHC class I, II and ICAM-1 by podocytes could in vitro be simulated by IFN-gamma. IFN-alpha weakly induced MHC class I, while IL-1 beta and TNF-alpha were ineffective. We hypothesize that podocytes in this in vivo model are important to maintain the local inflammatory process in the glomerulus by expression of relevant adhesion molecules and MHC molecules upon stimulation with specific cytokines.

Animals↗

PubMed1994

Anti-neutrophil cytoplasmic antibodies: a new class of autoantibodies in glomerulonephritis, vasculitis and other inflammatory disorders.

Anti-neutrophil cytoplasmic antibodies (ANCA) constitute a new group of antibodies that are directed against myeloid proteins. Several antigens recognized by ANCA have been described. Antibodies directed to proteinase 3, myeloperoxidase and/or elastase are closely associated with necrotizing systemic vasculitis and/or necrotizing and crescentic glomerulonephritis. Changes in levels of anti-proteinase 3 in generally reflect disease activity in Wegener's granulomatosis. The diagnostic significance of other or still unknown specificities has not yet been definitely established. Recent data from in vitro and in vivo models suggest a role for ANCA in the pathogenesis of systemic vasculitides and/or necrotising and crescentic glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1993

Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model.

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H2O2, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra- and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN.

Animals↗

PubMed1993

Induction of an humoral and cellular (auto) immune response to human and rat myeloperoxidase(MPO) in Brown-Norway(BN), Lewis and Wistar Kyoto(WKY) rat strains.

Anti-MPO and anti-proteinase 3 antibodies are strongly associated with certain forms of vasculitis and glomerulonephritis and a pathophysiological role for the antibodies has been hypothesized (Kallenberg et al. 1991). To test this hypothesis WKY, Lewis and BN rats were immunized with human MPO. BN rats developed a strong humoral response, cross reacting with autologous MPO, and Lewis rats a strong cellular response to human MPO.

Animals↗

PubMed1993

Use of an immunoglobulin M containing preparation for treatment of two hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.

This report describes two hypogammaglobulinemic patients with persistent Campylobacter jejuni infections in spite of IgG substitution and antibiotic therapy. Since serum bactericidal activity (SBA) depends on IgM, these patients were each treated with six doses of an IgM-containing immunoglobulin preparation (Pentaglobin) at three-week intervals. During IgG therapy SBA was not seen in either patient. However, one hour following administration of the IgM preparation, SBA increased to 90%. Just before the next dose SBA was still at the 30-70% level. Both patients tolerated the therapy very well and there were no culture-confirmed relapses of Campylobacter jejuni infection. The IgM preparation may therefore be a useful alternative to conventional IgG in the treatment of hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.

Adult↗

PubMed1993

Attenuation of anti-Thy1 glomerulonephritis in the rat by anti-inflammatory platelet-inhibiting agents.

Although both ecto-ADPase and prostacyclin (PGI2) inhibit platelets and neutrophils, their action in acute glomerulonephritis is unknown. We tested the PGI2 analog Iloprost and 2chloroadenosine (2Cl-ADO), an analog of adenosine, the end product of nucleotidase activities, during anti-Thy1 nephritis. Rats received anti-Thy1 immunoglobulin G (5 mg/kg body weight, intravenously) and subsequently one subcutaneous injection of either 2Cl-ADO (10 mg/kg body weight; (n = 6) or Iloprost (1 mg/kg body weight; n = 6). Control rats received anti-Thy1 immunoglobulin G with saline (n = 6) or saline alone (n = 6). After 24 hours, kidneys were processed for light-microscopical evaluation. Proteinuria was studied in additional rats. Results showed that both drugs inhibited intraglomerular platelet activation (P < 0.005). 2Cl-ADO also reduced intraglomerular O2- production of neutrophils (P < 0.05), in contrast to Iloprost. Intraglomerular immunoglobulin G deposition, complement activation, neutrophil influx, and myeloperoxidase release were not affected by 2Cl-ADO or Iloprost. However, proteinuria was completely prevented by both drugs. It is concluded that PGI2 and nucleotidases are potentially able to attenuate this form of nephritis by inhibiting platelet activity, whereas nucleotidases also inhibit neutrophil activity in vivo.

2-Chloroadenosine↗

PubMed1991

Inhibition by lipid A-specific monoclonal antibodies of priming of human polymorphonuclear leucocytes by endotoxin.

Exposure to lipopolysaccharide (LPS) primes polymorphonuclear leucocytes (PMNL) for enhanced release of oxygen metabolites after subsequent stimulation. The metabolic response of human PMNL primed with LPS and stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP) was measured by chemiluminescence (CL) as a parameter for endotoxic activity. Polymyxin B (PMB) and monoclonal antibodies (MAbs) with specificity for lipid A were tested for inhibition of the priming effect of Re LPS of Salmonella minnesota R595, Rc LPS of Escherichia coli J5 and smooth LPS of E. coli O111. The CL response of PMNL primed with Re LPS or Rc LPS was higher than that of PMNL primed with smooth LPS. Pre-incubation of rough or smooth LPS with PMB caused dose-dependent inhibition of priming of PMNL. Two IgM MAbs, 8-2 and 26-20, which recognise different epitopes on the hydrophobic part of lipid A, also completely prevented priming of PMNL by either rough or smooth LPS. The dose-dependent inhibitory effect of both MAbs was similar to the inhibition by PMB. These results indicate that the binding of MAbs to the hydrophobic part of lipid A is important in blocking lipid A-mediated effects.

Antibodies, Monoclonal↗

PubMed1991

Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders.

In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly of the IgG1 and IgG4 subclass in all groups of patients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgG1 levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgG1 and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.

Adult↗

PubMed1990

[Polypharmacy in patients of a geriatric department of a general hospital].

At three somato-geriatric and one psychogeriatric units in the Amsterdam 'Slotervaartziekenhuis', retrospective research into the use of drugs by all patients admitted in 1985 (n = 724) was conducted. The main aim was to answer the question whether geriatric treatment can reduce the hitherto frequently described polypharmacy of the elderly. For that purpose the medication of all patients is registered as from their admission into hospital until the time of discharge from hospital. The average number of drugs used in the hospital appeared to have increased from 2.8 on admission to 3.8 on discharge. Geriatricians in Amsterdam were unable to reduce polypharmacy, probably because of the multiple pathology of their patients (4.4 diagnoses on discharge per patient). Yet, they prescribed only 0.86 drug per diagnosis on average. The most frequently prescribed drugs were vitamins, laxatives, diuretics, analgetics, sedatives/hypnotics and cardiovascular drugs. Antibiotics were used by a large percentage (46%) of the patients. On admission clearly fewer drugs (2.4) were used by patients who lived independently than by patients from residential and nursing homes (respectively 4.1 and 3.6). Eight percent of the patients was admitted because of adverse drug reactions or intoxications. On admission they used an average number of 4.1 drugs daily, which is considerably more than the number (2.7) used by other patients. Their drug use of course was reconsidered during their stay at the geriatric department.

Aged↗

PubMed1989

Binding characteristics and cross-reactivity of three different antilipid A monoclonal antibodies.

A detailed characterization of binding specificity and cross-reactivity of three antilipid A murine mAb was performed. Binding characteristics of these three mAb were investigated against Ag (ReLPS, lipid A, derivatives of lipid A) in solid phase (ELISA) and in fluid phase (C consumption, inhibition studies), and upon incorporation in membranes (E: passive hemolysis assay, and liposomes: inhibition studies). Cross-reactivity with heterologous Ag was investigated in ELISA (LPS, Gram-negative bacteria) and immunoblot experiments (LPS). The binding specificity of mAb 26-5 (IgG2b), raised against synthetic lipid A, was located in the hydrophilic region of biphospholipid A and was also exposed after membrane incorporation of lipid A or after preincubation of lipid A with polymyxin B (PMX). mAb 26-20 (IgM), also raised against synthetic lipid A, showed binding specificity for the hydrophobic region of lipid A: no binding to membrane-associated lipid A could be demonstrated, and binding in ELISA could be blocked very efficiently by PMX. The reaction pattern of mAb 8-2 (IgM), raised against the heat-killed Re mutant of Salmonella typhimurium, was in part similar to that of mAb 26-20. However, inhibition of binding with PMX was less efficient and a high specificity for ReLPS, also after membrane incorporation of this Ag, was demonstrated. In contrast to mAb 26-5 and 26-20, mAb 8-2 showed extensive cross-reactivity with heterologous LPS preparations and heat-killed as well as live Gram-negative bacteria. It is concluded that each of the three mAb binds to a different antigenic epitope in lipid A and that exposure of those epitopes for antibody binding is restricted in a differential manner, depending on mode of Ag presentation. The here defined reaction patterns provide a basis for the interpretation of potential inhibitory effects on in vitro and in vivo biologic (and toxic) activities of endotoxins and Gram-negative bacteria.

Animals↗

PubMed1982

The fate of N-nitrosodiethanolamine after oral and topical administration to rats.

14C-labelled N-nitrosodiethanolamine ([14C]NDELA) was given to Osborne-Mendel rats at two dose levels, 0.5 or 50 mg/kg, by oral or topical administration. The excreta and tissues were analysed at various times from 4 hr to 1 wk after administration to determine the distribution of radioactivity. After oral administration, [14C]NDELA was rapidly absorbed from the gastro-intestinal tract, distributed throughout all organs and tissues, and then excreted, mainly via the kidneys. The tissue concentration reached a peak at 8 hr, but some activity remained after 1 wk. After topical application NDELA was slowly absorbed percutaneously, but once absorbed was distributed as in the orally dosed rats. Metabolic profiles of urine and bile samples from both the orally and topically dosed rats were identical, although the quantities varied. In addition to unchanged NDELA, one metabolite was present. The dose level had little effect on the quantities of unchanged NDELA or the metabolite present.

Administration, Oral↗

PubMed1978

Biliary excretion of [14C]penicillic acid by rats.

Adult male rats were given [14C]penicillic acid by oral intubation, and the biliary excretion of the compound was monitored. The significance of bile as an excretory route was confirmed and compared by using open and recycle cannulation of the bile duct. The biological half-retention life of [14C]penicillic acid in the bile was 3.63 h.

Animals↗

PubMed1977

Intermediate-duration toxicity study of patulin in rats.

The toxicity of patulin was studied in two generations of Sprague-Dawley rats over a period of approximately 10 months. Patulin in 1 mM citrate buffer was administered by gavage to FO generation rats at a dose level of 0, 1.5, 7.5, or 15.0 mg/kg a body weight five times a week for 10-14 wk; females were treated seven times a week during pregnancy. High mortality and insufficient progeny in the groups given 7.5 and 15.0 mg/kg made it impossible to continue those two regimens into the second generation. The study was continued for 20-23 wk with F1A generation animals given 1.5 mg/kg and controls. The only lesion found at necropsy that could be attributed to patulin administration was gaseous distention of the gastrointestinal tract, which was probably the result of the antibiotic effect of this mycotoxin on the normal intestinal flora. A decreased weight gain in male rats of the FO generation was dose-related. An impairment in growth rates of F1A and F2A progeny of both sexes was statistically significant at the 1.5 mg/kg dose level. Fetuses taken from patulin-treated females on day 20 of pregnancy were noticeably smaller than controls fetuses and the difference was significant for F2A males. No other teratological abnormalities related to patulin dosing at the 1.5 mg/kg level were observed consistently in either F1A or F2A fetuses. Patulin did not appear to produce dominant lethal effects at dose levels up to 15.0 mg/kg when given by gavage to the males five times a week for 10 or 11 wk.

Animals↗

PubMed1973