Publications by authors named "Vermylen Jos"

It was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its possible association with vascular outcomes. The prevalence of non-responders to aspirin in 64 populations from 53 studies, comprising 6,450 subjects, had a median value of 0.27.

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Megakaryocytes and platelets express the Gs-coupled VPAC1 receptor, for which the pituitary adenylyl cyclase-activating peptide (PACAP) and the vasointestinal peptide (VIP) are agonists. We here demonstrate a regulatory role for VPAC1 signaling during megakaryopoiesis. A total of 2 patients with trisomy 18p with PACAP overexpression and transgenic mice overexpressing PACAP in megakaryocytes have thrombopathy, a mild thrombocytopenia, and a reduced number of mature megakaryocytes in their bone marrow.

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Background: The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hypothesized that the metabolic syndrome, of which obesity is an important component, might be related to genetic variation in RGS2.

Methods And Results: We screened the human RGS2 gene.

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Objectives: A clinical trial, "Belgian Improvement Study on Oral Anticoagulation Therapy (BISOAT)," significantly improved the quality after implementing four different quality-improving interventions in four randomly divided groups of general practitioners (GPs). The quality-improving interventions consisted of multifaceted education with or without feedback reports on their performance, international normalized ratio (INR) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy. The quality improvement in INR control versus baseline was similar in the four groups.

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Objective And Importance: We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with immediate and important pain relief for 3 years.

Clinical Presentation: A 12-year-old boy experiencing primary erythromelalgia had a 4-year history of recurrent attacks of severe burning pain in both feet, accompanied by local reddening, swelling, and heating of the skin. The attacks were triggered by warmth and exercise.

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The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only.

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Objective: In Belgium oral anticoagulation therapy is mainly supervised by general practitioners (GPs). This study aims to evaluate the quality of management of oral anticoagulation by Belgian GPs and to verify the relation between time in range and a set of potentially influencing co-variables.

Methods: In a retrospective cross-sectional study, involving 66 GP-practices, the INR-values obtained over a 6-month period were analysed.

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The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. beta1-tubulin is the major isoform within platelet and megakaryocyte microtubules. In 24.

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Aims: In Belgium, general practitioners (GPs) mainly manage oral anticoagulation therapy. To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions, a randomized clinical trial was performed.

Methods And Results: Stratified randomization divided 66 GP-practices into four groups.

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Background: Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).

Methods And Results: We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 microg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy.

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Shear stress triggers von Willebrand factor (VWF) binding to platelet glycoprotein Ibalpha and subsequent integrin alpha(IIb)beta(3)-dependent platelet aggregation. Concomitantly, nucleotides are released from plateletdense granules, and ADP is known to contribute to shear-induced platelet aggregation (SIPA). We found that the impaired SIPA of platelets from a Hermansky-Pudlak patient lacking dense granules was restored by exogenous l-beta,gamma-methylene ATP, a stable P2X(1) agonist, as well as by ADP, confirming that in addition to ADP (via P2Y(1) and P2Y(12)), ATP (via P2X(1)) also contributes to SIPA.

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The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide of the vasoactive intestinal peptide/secretin/glucagon superfamily. Studies in two related patients with a partial trisomy 18p revealed three copies of the PACAP gene and elevated PACAP concentrations in plasma. The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels.

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Although drugs exist for the primary and secondary prevention of thrombosis, more potent antiplatelet drugs with sufficiently wide therapeutic windows to avoid bleeding complications are needed. Both academic and pharmaceutical laboratories are working to develop such drugs. This chapter reviews the potential of inhibiting interactions between von Willebrand factor (vWF) and the second most abundant receptor on the platelet, the glycoprotein (GP) Ib/IX/V complex, interactions that are essential for the activation of circulating platelets, contacting a vessel wall injury.

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The ATP-gated P2X1 ion channel is the only P2X subtype expressed in human platelets. Via transmission electron microscopy, we found that P2X1 mediates fast, reversible platelet shape change, secretory granule centralization, and pseudopodia formation. In washed human platelets, the stable P2X1 agonist alpha,beta-methylene ATP (alpha,beta-meATP) causes rapid, transient (2-5 s), and dose-dependent myosin light chain (MLC) phosphorylation, requiring extracellular Ca2+.

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The C2 domain of factor VIII (FVIII) mediates FVIII binding to von Willebrand factor (VWF) and phospholipids (PLs), thereby determining the stability and the activity of FVIII. A deletion of Ala2201 (Del2201) was identified in the FVIII C2 domain of 2 unrelated patients with mild hemophilia A (FVIII:C 11%-33%). This mutation prevents FVIII binding to a human monoclonal antibody recognizing the C2 domain and inhibiting FVIII binding to VWF and phospholipids.

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Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEPs) are prothrombotic. Here, we investigated the time course and the mechanisms.

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The paternally expressed extra-large stimulatory G protein gene (XLalphas) is a splice variant of the stimulatory G-protein gene (Gsalpha) consisting of XL-exon1 and exons 2-13 of Gsalpha. A second open reading frame (ORF) in XL-exon1, that completely overlaps the XL-domain ORF, encodes ALEX, which is translated from the XLalphas mRNA and binds the XL-domain of XLalphas. We previously demonstrated that a paternally inherited functional polymorphism in XL-exon1, consisting of a 36 bp insertion and two nucleotide substitutions, is associated with Gs hyperfunction in platelets, leading to an increased trauma-related bleeding tendency and is accompanied by neurological problems and brachydactyly in two families.

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We have generated transgenic mice overexpressing the human P2X(1) ion channel in the megakaryocytic cell lineage. Platelets from transgenic mice exhibited a gain of P2X(1) ionotropic activity as determined by more prominent P2X(1)-mediated Ca(2+) influx and platelet shape change. P2X(1) overexpression enhanced platelet secretion and aggregation evoked by low doses of collagen, convulxin, or the thromboxane A(2) mimetic U46619.

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Erythroid and megakaryocytic lineage differentiation and maturation are regulated via cooperation between transcription factor GATA1 and its essential cofactor friend-of-GATA1 (FOG1). The interaction between these two murine proteins is well studied in vitro and depends on the binding of Fog1 to the N-terminal zinc finger (N-finger) of Gata1. We identified the human FOG1 gene on chromosome 16q24 and found expression mainly in hematopoietic cells and also in several other tissues.

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Platelet adhesion to damaged vessel wall and shear-induced platelet aggregation necessitate binding of the von Willebrand factor (VWF) A1 domain to platelet GPIbalpha. Blocking this interaction represents a promising approach to the treatment of arterial thrombosis. Comparison of amino acid sequences of the VWF A1 domain in several species, expressing VWF recognized by the blocking monoclonal antibody AJvW-2, suggested 9 residues (His563, Ile566, Asp570, Ala581, Val584, Ala587, Arg616, Ala618, and Met622) to contribute to the epitope for AJvW-2 or to be part of the GPIbalpha-binding site.

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We previously showed that beta(2)-glycoprotein I (beta(2)GPI)-dependent lupus anticoagulants (LAs) form bivalent antigen-antibody complexes with high affinity for phospholipids; these complexes are responsible for their in vitro anticoagulant effect. We now studied the role of these bivalent complexes in arterial thrombosis in the hamster. Three monoclonal antibodies (mAbs) raised against human beta(2)GPI were selected on the basis of their cross-reactivity with hamster beta(2)GPI.

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Mild/moderate hemophilia A patients carrying certain mutations in the C1 domain of factor VIII (FVIII) have a higher risk of inhibitor occurrence. To analyze the mechanisms responsible for inhibitor development in such patients, we characterized FVIII-specific CD4(+) T-cell clones derived from a mild hemophilia A patient carrying an Arg2150His substitution in the C1 domain and who presented with a high titer inhibitor toward normal but not self-FVIII. All T-cell clones recognized synthetic peptides encompassing Arg2150.

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Pseudohypoparathyroidism Ib (PHPIb), characterized by parathyroid hormone-resistant hypocalcemia and hyperphosphatemia, is caused by a deregulation in the imprinting status of the GNAS1 cluster, comprising exons XL, NESP55 and 1A and the coding exons of Gsalpha. Differences in methylation of exon 1A and sporadically also of exons XL and NESP55 were found and thought to result in long-range effects on Gsalpha expression, limited to the proximal renal tubules. The exact imprinting defect is not precisely localized, and the expected differences in Gsalpha protein level and function are mainly hypothetical.

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