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Biomedical subjects

B Ringertz

Publications and source records attributed to B Ringertz.

At least 19 recordsLinked to original sources
PubMed1997

Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.

The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.

Adolescent↗
PubMed1997

Olsalazine-induced lupus syndrome.

A 73 year-old woman with ulcerative colitis developed skin rashes after long-standing sulphasalazine treatment. After a switch to olsalazine, she developed a severe SLE with multiorgan involvement. When the treatment was terminated, the disease manifestations and serological findings resolved.

Aged↗
PubMed1995

Mechanisms for lipoxin A4-induced neutrophil-dependent cytotoxicity for human endothelial cells.

In a model of vasculitis we have evaluated mechanisms for how neutrophil polymorphonuclear granulocytes (PMNs) kill cultured human umbilical vein endothelial cells (HUVECs) in vitro (as release of chromium 51) in response to the double dioxygenation product of arachidonic acid, lipoxin A4 (LXA4) and to formyl-methionyl-leucyl-phenylalanine (fMLP). The cytolysis induced by LXA4 and fMLP was dose dependent, with maximum values at 100 nmol/L (which caused a 2.7-fold and 2.3-fold increases of 51Cr release, respectively, relative to buffer-treated controls). LXA4 also conferred a peak of cytotoxicity at 0.1 nmol/L (which caused a 2.2-fold increase in 51Cr release). Leukotriene B4, platelet activating factor (PAF), and zymosan-activated serum were inefficient. Phorbol myristate acetate caused the most prominent cytotoxicity, which was first evident at 1 mumol/L. The LXA4 effect was abrogated by superoxide dismutase, catalase, alpha 2-macroglobulin, and alpha 1-antitrypsin but not by mannitol. Addition of a monoclonal antibody (mAb) to CD18 also inhibited neutrophil-dependent cytotoxicity to LXA4 and fMLP. MAbs to intercellular adhesion molecule-1 or P-selectin blocked 100% and 52%, respectively, of the LXA4-induced cytotoxicity. Neutrophils from a patient with chronic granulomatous disease were incapable of mediating any cytotoxicity. The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086 and by treating neutrophils with pertussis toxin. Thus this novel effect of LXA4, as a potent promoter of neutrophil-mediated cytotoxicity for HUVECs, is a process dependent on PMN adhesion proteins, oxygen radicals, and proteases, and it is apparently associated with endogenous PAF expression and requires pertussis-sensitive G proteins.

Catalase↗
PubMed1995

Neutrophil membrane potential changes and homotypic aggregation kinetics are pH-dependent: studies of chronic granulomatous disease.

Activated polymorphonuclear neutrophil granulocytes (PMN) from patients with chronic granulomatous disease (CGD) show reduced electron-proton shifts and an inability to acidify the cell. We studied whether this impaired pH-regulating capacity affected PMN membrane potential changes and the kinetics of homotypic aggregation by changing the extracellular pH over a wide range. At pH 7.4 normal PMN showed a rapid, transient membrane depolarization to leukotriene B4 (LTB4) and a slower response to N-formyl-methionyl-leucyl-phenylalanine. In contrast, PMN from 13 patients with CGD exhibited no or minute depolarization to these stimuli and 77% of tested patients with CGD displayed absence or marked reductions of the disaggregation to LTB4. On acidification of pH 5.0 to 6.4, PMN membrane depolarization appeared in six of nine tested patients. Likewise, disaggregation became evident in all of three patients. On alkalinization of normal PMN to pH 8.0 to 9.0, membrane depolarization and disaggregation to LTB4 disappeared, and cells reacted as CGD PMN. This change was not due to inefficient signal transduction, because normal PMN enhanced the superoxide ion production to N-formyl-methionyl-leucyl-phenylalanine on this alkalinization. Cytosolic pH changes in resting and LTB4-activated CGD cells at pH 6.0, 7.4, and 8.5 were similar those in control cells but for absence of an initial acidification. Thus neutrophil membrane potential changes and aggregation kinetics to LTB4 are abnormal in patients with CGD and return toward normal on extracellular acidification.

Adolescent↗
PubMed1994

Lipoxin A4 induces neutrophil-dependent cytotoxicity for human endothelial cells.

The authors have assessed the capacity of neutrophil granulocytes (PMN) to kill cultured human umbilical-vein endothelial cells (HUVEC) in vitro (as release of 51Cr) in response to the recently described double dioxygenation product of arachidonic acid, lipoxin A4 (LXA4). LXA4 conferred a marked cytotoxicity, whereas formyl-methionyl-leucyl-phenylalanine (fMLP) was less potent. The LXA4 and fMLP effects were dose dependent, with a maximum at 100 nM (which caused 2.7- and 2.3-fold increases of 51Cr release, respectively, relative to buffer-treated controls). The LXA4 and fMLP responses increased with the PMN concentration, depended on the fetal calf serum concentration, incubation temperature and duration and the presence of calcium and magnesium ions.

Cells, Cultured↗
PubMed1994

[Rheumatologists' current tasks].

The main tasks for contemporary rheumatology include finding methods for the early identification of patients with inflammatory arthropathy, the use and development of prognostic indicators of the degree of aggressiveness required in treatment, and well structured and comprehensive follow-up treatment modalities administered in new ways and of the many new modalities that are under development. Success in these respects will entail close liaison with primary care and with other related disciplines. Dynamic developments are to be expected concerning the introduction of new generations of immunoregulatory agents.

Adjuvants, Immunologic↗
PubMed1993

The effect of endothelin, neuropeptide Y, calcitonin gene-related peptide and substance P on neutrophil functions.

Neuropeptides are putative mediators of inflammation. At physiological concentrations substance P has been shown to prime polymorphonuclear neutrophil granulocyte (PMN) chemiluminescence (CL). In the present study we show also that both endothelin and neuropeptide Y (NPY), but not calcitonin gene-related peptide (CGRP) are able to prime PMN oxidative metabolism. At similar nanomolar concentrations SP and endothelin (but not NPY) also primed formyl-methionyl-leucyl-phenylalanine (fMLP)-induced rises of cytosolic calcium. On the other hand, NPY caused a direct and dose-related increase of cytosolic calcium concentrations. None of the mentioned neuropeptides primed PMN aggregation or directly induced CL, aggregation or chemotaxis over a wide range of concentrations (1 fM-1 microM).

Calcitonin Gene-Related Peptide↗
PubMed1991

Ethanol impairs certain aspects of neutrophil adhesion in vitro: comparisons with inhibition of expression of the CD18 antigen.

Since ethanol impairs polymorphonuclear leukocyte (PMNL) delivery to inflammatory sites, the effect of ethanol on PMNL adhesiveness was studied in vitro. Ethanol inhibited PMNL aggregation induced by formylmethionylleucylphenylalanine (FMLP) but not by phorbol myristate acetate (PMA), whereas responses to both stimuli were abolished by treating PMNL with monoclonal antibody 60.3 (against the adhesion protein CD18). This antibody also abrogated spontaneous and FMLP-stimulated PMNL adhesion to plastic, whereas ethanol reduced spontaneous but not FMLP-induced adherence. Chemotaxis in Boyden or agarose systems was not diminished by ethanol, but high concentrations of MAb 60.3 inhibited migration under agarose. Nonetheless, upregulation of cell surface expression of CD18 (assessed by immunofluorescence flow cytometry) induced by FMLP or PMA was similarly reduced by ethanol. Thus, ethanol inhibited only certain of PMNL adhesion, and although the stimulated up-regulation of CD18 expression was reduced it is unlikely that ethanol effects were mediated only by this inhibition.

Antigens, CD↗
PubMed1991

The effect of 20-trifluoromethyl leukotriene B4 on neutrophil functional responses.

20-trifluoromethyl-leukotriene B4 (20CF3-LTB4) is a stable derivative of leukotriene B4 (LTB4) that is not subjected to omega-oxidation to less active metabolites. 20CF3-LTB4 was as potent as LTB4 as a chemotactic, adhesion-promoting and aggregatory agent for human neutrophils, but had only 11 +/- 3% of the ability to induce an oxidative response. Nonetheless, both compounds were equally efficient in order to confer a rapid and monophasic increment of the concentration of cytosolic calcium. The kinetics of the calcium, aggregatory and chemiluminescent responses to 20CF3-LTB4 were similar to that of LTB4. These findings suggest that the insertion of the trifluoromethyl group into the LTB4 molecule causes a shift of the biological activity profile, suggesting that 20CF3-LTB4 binds mainly to high affinity LTB4 receptors. Moreover, the similarity of the response kinetics of LTB4 and 20CF3-LTB4 suggests that the mechanism for the rapid and transient responses of LTB4 is not due to its omega-oxidation.

Calcium↗
PubMed1991

Effects of an essential fatty acid-supplemented diet on leukotriene B4-induced rat neutrophil functions.

This study evaluated the effect of dietary supplementation with the essential fatty acid linoleic acid to 10% of the energy content of a diet on the stimulus-response coupling of rat peritoneal neutrophils. When stimulated with leukotriene B4 neutrophils from essential fatty acid supplemented rats responded with a significantly more pronounced oxidative metabolism (assessed as luminol augmented chemiluminescence) relative to control cells from rats on a normal 3% of total energy essential fatty acid diet. Chemiluminescence response to the formylpeptide N-formyl-norleucyl-leucyl-phenylalanine-norleucyl-thyrosyl-leucine was similarly enhanced. In contrast, responses elicited by the lectin concanavalin A did not differ between the two dietary groups. In response to leukotriene B4 a dose-related inhibition of neutrophil aggregation was observed, whereas chemotaxis did not differ between the two groups. Thus, linoleate supplementation is associated with a stimulus-specific modulation of neutrophil oxidative and aggregatory responses suggesting an effect on early, conceivably receptor-linked, steps of the stimulus-response coupling.

Animals↗
PubMed1991

Antirheumatic effects of fasting.

Total fasting induces within a few days a substantial reduction of joint pain, swelling, morning stiffness, and other arthritic symptoms in patients with rheumatoid arthritis. This remission subsides slowly after discontinuation of fasting. Its mechanisms are complex and involves diminished activation of neutrophils and lymphocytes and decreased generation of leukotrienes and of concentrations of serum complement factors, as well as of other proinflammatory systems. Moreover, ketosis and other metabolic and endocrine changes may be of significance for symptom expression and recognition.

Arthritis, Rheumatoid↗
PubMed1990

Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium.

As the neutrophil granulocyte plays an important part in rheumatoid inflammation the effect of sulphasalazine on neutrophil function was studied. The results show that sulphasalazine, and its metabolite sulphapyridine, inhibit neutrophil superoxide production elicited by the receptor mediated stimulus N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and by the calcium ionophore A23187. This effect seems to be dependent on inhibition of intracellular Ca++ increase as both substances reduce this increase upon cell activation with fMLP and A23187. Sulphasalazine and sulphapyridine do not inhibit superoxide production after stimulation with the ester phorbol myristate acetate, a stimulus response coupling which is independent of intracellular Ca++ increase. The reported inhibition of superoxide generation may explain, at least partly, the antirheumatic property of sulphasalazine.

Calcimycin↗