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Biomedical subjects

J Jansen

Publications and source records attributed to J Jansen.

At least 109 records · Page 6Linked to original sources

Identification of type-2 phosphatidic acid phosphohydrolase (PAPH-2) in neutrophil plasma membranes.

Plasma membrane phosphatidic acid phosphohydrolase (PAPH) plays an important role in signal transduction by converting phosphatidic acid to diacylglycerol. PAPH-2, a Mg(2+)-independent, detergent-dependent enzyme involved in cellular signal transduction, is reportedly absent from the plasma membranes of neutrophilic leukocytes, a cell that responds to metabolic stimulation with abundant phospholipase D-dependent diacylglycerol generation. The present study was designed to resolve this discrepancy, focusing on the influence of cellular disruption techniques, detergent availability and cation sensitivity on the apparent distribution of PAPH in neutrophil subcellular fractions. The results clearly indicate the presence of two distinct types of PAPH within the particulate and cytosolic fractions of disrupted cells. Unlike the cytosolic enzyme, the particulate enzymes was not potentiated by magnesium and was strongly detergent-dependent. The soluble and particulate enzymes displayed dissimilar pH profiles. Separation of neutrophil particulate material into fractions rich in plasma membranes, specific granules and azurophilic granules by high speed discontinuous density gradient centrifugation revealed that the majority of the particulate activity was confined to plasma membranes. This activity was not inhibited by pretreatment with n-ethyl-maleimide in concentrations as high as 25 mM. PAPH activity recovered in the cytosolic fraction of disrupted neutrophils was almost completely inhibited by 5.0 mM n-ethylmaleimide. We conclude that resting neutrophils possess n-ethylmaleimide-resistant PAPH (type 2) within their plasma membranes. This enzyme may markedly influence the kinetics of cell activation by metabolizing second messengers generated as a result of activation of plasma membrane phospholipase D.

Cell Membrane↗

Two-dimensional one-pulse rotational echo spectra.

Recently a two-dimensional representation of one-dimensional spinning sideband magic-angle spinning (MAS) spectra has been published with applications to deuteron MAS nuclear magnetic resonance (NMR). The introduction of a new time axis, based on the rotor period, allows the separation of isotropic and anisotropic chemical shifts. It is shown here that, in addition to untangling spinning sideband spectra, data-processing steps can be incorporated which enabled applications of the method to signals from nuclei with anisotropies smaller than those of the quadrupole coupling of deuterons. This is achieved by linear prediction of the rotary echo signals. Advantages and limitations of the algorithm are discussed and demonstrated with experimental results of 13C cross-polarization (CP) MAS spectra of glycine.

Algorithms↗

Soluble receptors for tumor necrosis factor as predictors of progression to AIDS in asymptomatic human immunodeficiency virus type 1 infection.

Serum concentrations of soluble receptors for tumor necrosis factor-alpha (sTNF alpha R) types I and II, beta 2-microglobulin, and CD4 cell counts were determined at entry and 3-5 months before AIDS diagnosis in 20 untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1)-seropositive subjects, who progressed to AIDS within 5.5 years of study entry, and in an equal number of HIV-seronegative and untreated seropositive controls, who remained asymptomatic. At entry, concentrations of sTNF alpha R type II and beta 2-microglobulin were elevated and increased further in progressors. The odds ratio (OR) for sTNF alpha R type II concentrations > or = 6.5 ng/mL was 18.4 and for beta 2-microglobulin concentrations > or = 3 mg/L was 6.6; CD4 cell counts were not predictive. Five months before diagnosis, the OR was 102.0 for sTNF alpha R type II concentrations > or = 7.5 ng/mL, 13.5 for beta 2-microglobulin concentrations > or = 4 mg/L, and 6.9 for CD4 cell counts < 250/mm3 (counts < 500/mm3 were not predictive). Of the three variables, sTNF alpha R type II was proved by bivariate analysis to be the strongest and earliest predictor of disease progression.

Acquired Immunodeficiency Syndrome↗

Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood.

Sepsis and lipopolysaccharide (LPS) trigger the systemic release of both cytokines and catecholamines. Cytokines are known to be capable of eliciting a stress hormone response in vivo. The present study sought insight into the effect of noradrenaline on LPS-induced release of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6) in human whole blood. Whole blood was incubated with LPS for 4 h at 37 degrees C in the presence and absence of noradrenaline and/or specific alpha and beta antagonists and agonists. Noradrenaline caused a dose-dependent inhibition of LPS-induced TNF and IL-6 production. This effect could be completely prevented by addition of the specific beta 1, antagonist metoprolol, while it was not affected by the alpha antagonist phentolamine. Specific beta-adrenergic stimulation by isoprenaline mimicked the inhibiting effect of noradrenaline on LPS-evoked cytokine production, whereas alpha-adrenergic stimulation by phenylephrine had no effect. Fluorescence-activated cell sorter analysis demonstrated that beta-adrenergic stimulation had no effect on LPS binding to and internalization into mononuclear cells or on the expression of CD14, the major receptor for LPS on mononuclear cells. In acute sepsis, enhanced release of noradrenaline may be part of a negative feedback mechanism meant to inhibit ongoing TNF and IL-6 production.

Adult↗

Polarised interleukin 8 secretion by HT 29/19A cells.

Interleukin 8 is a neutrophil chemotactic and stimulating cytokine induced by various inflammatory stimuli, including tumour necrosis factor, interleukin 1, and endotoxin. The ability of HT 29/19A enterocytes to synthesise interleukin 8 was studied. The results show that interleukin 1 is an important stimulus for interleukin 8 synthesis and secretion by HT 29/19A cells, being more potent than tumour necrosis factor. The tumour necrosis factor and interleukin 1 induced interleukin 8 secretion by HT 29/19A cells was seen to be polarised according to the direction of stimulation. These results support the concept that mucosal cells (enterocytes) may play an important part in initiating mucosal inflammation. Furthermore, it is proposed that HT 29/19A cells constitute a tool to study stimulus directed polarised cytokine secretion.

Calcimycin↗

Treatment of methyl bromide poisoning with haemodialysis.

Acute accidental methyl bromide poisoning was treated with haemodialysis. The treatment was successful in removing bromide from the blood but the patient persists with severe neuropsychiatric sequelae. To the best of our knowledge haemodialysis has not been used previously for the treatment of organic bromide poisoning.

Acute Disease↗

Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection.

We investigated whether tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) are involved in the inflammatory reaction of Helicobacter pylori infection. In 23 patients with H. pylori infection and 16 patients with negative cultures for H. pylori and normal antral mucosa, the mucosal production of TNF-alpha, IL-1 beta, and IL-8 was measured in antral biopsy specimens after 23 h of in vitro culture. The levels of TNF-alpha and IL-1 beta appeared to be significantly higher in H. pylori-positive patients (p = 0.0002 for both TNF-alpha and IL-1 beta). IL-8 production was also higher in H. pylori-infected subjects, but this difference did not reach statistical significance (p = 0.057). No significant differences were found between the level of the cytokines in H. pylori-infected patients with or without duodenal ulcer disease. A strong correlation was found between the production of IL-1 beta and IL-8. The biologic effects of these cytokines may explain the conspicuous recruitment, influx, and activation of neutrophils in the gastric mucosa during H. pylori infection.

Adult↗

Increase of sTNF receptor levels in acute renal allograft rejection after treatment with OKT3.

The use of OKT3 is associated with severe clinical side-effects. Adverse reactions are partly attributed to release of tumour necrosis factor (TNF). TNF binds to two receptors on the outer membranes of most human cell lines. Shedding of these proteins (sTNFR-p55 and sTNFR-p75) may block biological effects of TNF. Here we show a fair correlation between serum levels of sTNFRs and renal function as measured by glomerular filtration rate (GFR). In addition we assessed levels of sTNFR-p55 and sTNFR-p75, corrected for reduced renal clearance, in renal allograft rejection and following treatment with OKT3. Corrected serum levels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12 renal allograft patients treated for an acute rejection episode with either OKT3 or methylprednisolone (MPNS). Serum levels of CSLsTNFR-p55 and CSLsTNFR-p75 in both groups prior to anti-rejection treatment were not elevated. CSLsTNFRs peaked at 1 h after the administration of OKT3, whereas in the MPNS group CSLsTNFRs remained unchanged. We conclude that in acute renal transplant rejection CSLsTNFRs increase after treatment with OKT3. In spite of high circulating sTNFRs levels all OKT3-treated patients suffered from clinical side-effects.

Adult↗

Parallel up-regulation of CD11B and CD45 on neutrophilic leukocytes exposed to soluble factors of oral pathogens.

We tested culture supernatants from a battery of oral bacterial strains for their ability to influence the expression of CD11b and CD45 on the neutrophil plasma membrane. Several bacterial extracts stimulated the up-regulation of both CD11b and CD45 simultaneously. Two supernatants in particular (a clinical isolate of A. actinomycetemcomitans and F. nucleatum ATCC25586) potently stimulated the deployment of CD11b and CD45 from their intracellular storage site to the plasma membrane. Both supernatants inhibited superoxide release stimulated by exposure of neutrophils to formyl methionyl leucyl phenylalanine (FMLP) but had variable effects on superoxide release stimulated by phorbol myristate acetate (PMA). The ability of products of oral bacteria to modulate neutrophil plasma membrane antigen composition may regulate functional reactivity and thus be an important factor in the pathogenesis of periodontal infection and inflammation.

Antigens, CD↗

[Value, concept and efficacy of medical psychological examinations. Comments on the critique by A. Müller].

The authors discuss the re-orientation regarding the withdrawal of driving licences, aptitude tests, re-training of drivers and therapy for DUI offenders as proposed by Müller in "Blutalkohol" in 1993. The authors note that Müller's analysis refers to an examination practice which is outdated and no longer compatible with the current development of examination and consultation techniques used by officially recognised medico-psychological examination centres in Germany. Methodological misunderstandings and miscalculations in Müller's analysis are pointed out. In contrast, a diagnostic strategy is presented aiming not only at improving traffic safety but also at optimising justice for each individual case. This also aims at giving advice to DUI offenders on how to improve their fitness for driving using appropriate measures. Special emphasis is put on procedures which enable DUI-offenders to use their time of suspension to genuinely improve their driving fitness with the help of diagnostic and advisory bodies in the medico-psychological examination centres.

Adolescent↗

[Toxocara ova in parks and sand-boxes in the city of Utrecht].

An investigation was carried out for the presence of Toxocara spp. eggs in public parks and children's sand-boxes in the city of Utrecht. The pollution of parks with the eggs of the dog's ascarid Toxocara canis is comparable with reports from other European cities. The eggs of Toxocara cati were found in small numbers only. Interestingly there was no difference between parks with or without formal exclusion of dogs. Most sand-boxes are polluted with the eggs of the ascarid of cats T. cati. Incidentally eggs of T. canis were found. Sand-boxes which were obviously kept clean or could be closed contained lower numbers of eggs. As children playing in sand-boxes have far more chances to contaminate themselves with Toxocara eggs than when playing in parks or on playgrounds, the question arises if not T. cati eggs constitute a greater menace, at least in urban areas, to public health than T. canis eggs.

Animals↗

Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum.

The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of Plasmodium falciparum has been cloned. The Pfs48/45 gene is a non-interrupted, single copy gene that codes for a hydrophobic, non-repetitive protein of 448 amino acid residues containing a putative signal peptide at the N-terminus, a hydrophobic C-terminus and 7 potential N-glycosylation sites. Antibodies directed against a Pfs48/45-glutathione-S-transferase fusion protein reacted with both the 45-kDa and 48-kDa proteins of gametocytes. When Pfs48/45 is expressed in the baculovirus-insect cell system the recombinant Pfs48/45 protein is targeted and exposed to the insect cell surface in such a configuration that it is recognized by transmission-blocking anti-45/48-kDa monoclonal antibodies.

Amino Acid Sequence↗

Cost-benefit analysis of a screening strategy for Salmonella enteritidis in poultry.

Salmonella enteritidis is an emerging problem in several industrial countries. Outbreaks caused by this organism are almost always associated with the consumption of eggs and egg-products originating from infected poultry flocks. To reduce human infection, elimination of contaminated flocks could be considered. In this study we estimated the effectiveness of such a measure to reduce human infections. If poultry flocks are screened for S. enteritidis only once during their laying period, there is a 43.7% reduction in contaminated eggs. The effectiveness increases if the frequency of screening is increased, resulting in a 65.4% reduction in contaminated eggs after three screenings. The costs of this intervention strategy are determined by both the costs of screening and the economic losses of destroying poultry flocks.

Animals↗

Release of soluble receptors for tumor necrosis factor in clinical sepsis and experimental endotoxemia.

To assess the role of tumor necrosis factor (TNF) in the appearance of soluble TNF receptors (sTNFRs), 20 consecutive patients with a clinical diagnosis of sepsis were studied as were 7 chimpanzees after administration of endotoxin (4 ng/kg) with or without pentoxifylline. The patients had markedly elevated serum levels of sTNFR-p55 and sTNFR-p75 compared with healthy controls (P < .0001 for both receptors). The levels of both soluble receptors correlated with simultaneously measured immunoreactive TNF concentrations (p55: r = .63, P < .01; p75: r = .69, P < .001). In the chimpanzees, endotoxin induced subsequent rises in the serum concentrations of TNF and sTNFRs. Although pentoxifylline reduced the TNF response to intravenous endotoxin to 20% (P < .05), the appearance of sTNFRs was only moderately inhibited (sTNFR-p55 to 79% on average, P < .05; sTNFR-p75 to 77%, P = .12). These results indicate that TNF either does not play an important role in the appearance of sTNFRs in systemic infection or that a small amount of TNF remaining in the circulation after some bacterial challenges is sufficient to preserve the secretion of its soluble receptors.

Adult↗