document

Studies on the mechanism of fibrate-inhibited expression of plasminogen activator inhibitor-1 in cultured hepatocytes from cynomolgus monkey

Arts, J. (author), Kooistra, T. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Fibrates are widely used drugs in hyperlipidemic disorders. In addition to lowering serum triglyceride levels, fibrates have also been shown to reduce elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels in vivo. We demonstrate that fibrates suppress PAI-1 synthesis in cultured cynomolgus monkey hepatocytes in a concentration...

article 1997

document

Modulation of plasma fibrinogen levels by medication

de Maat, M.P.M. (author), Kodex, M. (author), Kastelein, J.J.P. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Elevated plasma fibrinogen levels represent an increased risk for cardiac events. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. Agents that have this capacity are the lipid lowering fibric acid derivatives (e.g. ciprofibrate) and the platelet aggregation inhibitor ticlopidine....

article 1996

document

Isolation and storage of DNA for population studies

Droog, S. (author), Lakenberg, N. (author), Meulenbelt, I. (author), de Maat, M.P.M. (author), Huisman, L.G.M. (author), Jie, A.F.H. (author), Slagboom, P.E. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

For genetic population studies, human genomic DNA is commonly isolated from peripheral blood. A fast, non-invasive DNA sampling method is developed involving oral samples taken with cotton swabs. In addition various procedures were compared for isolation of DNA from different sources: whole blood or buffy-coats stored at -20°C for 5-10 years or...

article 1996

document

Extracellular proteolysis and the migrating vascular smooth muscle cell

van Leeuwen, R.T.J. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Smooth muscle cells (SMC) form the major cell type in the arterial blood vessels. In the undamaged vessel wall they remain in a contractile state characterized by the absence of cell division, a low metabolic activity and a high actin-myosin content. As a reaction to injury of the vessel wall they can, however, change their phenotype and start...

article 1996

document

Genetic studies of complex diseases: Giant steps from promise to proof

Slagboom, P.E. (author), Kluft, C. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

article 1996

document

Interaction of reteplase with heparin. A comparison between reteplase and alteplase

Rijken, D.C. (author), Jie, A.F.H. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Reteplase is a protein consisting of the kringle-2 and protease domains of tissue-type plasminogen activator (t-PA). Because intravenous heparin will be used as an adjunct to thrombolytic therapy with reteplase, we investigated the interactions in vitro between heparin and reteplase as well as between heparin and recombinant t-PA (alteplase) as...

article 1996

document

Urokinase and tissue-type plasminogen activator stimulate human vascular smooth muscle cell migration

Wijnberg, M.J. (author), Nieuwenbroek, N.M.E. (author), Slomp, J. (author), Quax, P.H.A. (author), Verheijen, J.H. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

The objective of this study was to investigate the role of the plasminogen activation system in the migration of human vascular smooth muscle cells in vitro. After wounding of confluent human smooth muscle cell cultures by stripping cells from their extracellular matrix, cells start to migrate from the wounded edge into the denuded area....

article 1996

document

Prolonged circulation of tissue-type plasminogen activator in vivo by blocking mannose receptor- and lrp-mediated liver uptake

Kuiper, J. (author), van Teijlingen, M. (author), Vietsch, H. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Blessen, E.A.L. (author), Division of Biopharmaceutics, LACDR, Leiden, Netherlands Gaubius Laboratory TNO Preventie en Gezondheid (author)

A major complication of the use of of tissue-type plasminogen activator (t-PA) as fibrinolytic agent is its rapid clearance from the bloodstream. We have studied whether t-PA clearance can be reduced by preventing receptor-mediated endocytosis of t-PA in vivo via the mannose receptor and the low-density lipoprotein receptor related protein (LRP)...

article 1996

document

Regulation of t-pa expression by retinoic acid in cultured human endothelial cells in vitro and in rats in vivo

Lansink, M. (author), Toet, K. (author), Emeis, J.J. (author), Kooistra, T. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

We and others have previously shown that retinoids (vitamin A derivatives) regulate t-PA synthesis in human endothelial cells in vitro and in rats in vivo. Retinoids exert their effect on t-PA expression via specific nuclear receptors, retinoic acid receptors (RARs). of which several subtypes and isoforms exist. Using subtype-specific retinoids...

article 1996

document

The use of Stabilyte® plasma may cause changes in pH in the assay of some fibrinolysis analytes and might effect results

Meijer, P. (author), van der Ham, F. (author), Kluft, C. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

The use of Stabilyte® plasma in the Coaliza® t-PA, Coaliza® PAI-1 and Enzygnost® PAP micro was evaluated. For PAI-1 antigen no, for t-PA antigen only small differences were observed between measurements in citrate and Stabilyte® plasma. For PAP-complexes significant lower (72%) results were obtained when Stabilyte® plasma was applied. This is...

article 1996

document

On the mechanism of the fibrin-specificity of staphylokinase

Sakharov, D.V. (author), Rijken, D.C. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Staphylokinase (STA), a protein of bacterial origin, was recently demonstrated to induce highly fibrin-specific thrombolysis both in human plasma in vitro and in limited clinical trials. Using fluorescence microscopy, we investigated the spatial distribution of FITC-labelled STA during lysis of a plasma clot and its binding to purified fibrin...

article 1996

document

The plasminogen activation system plays a role in the migration of human smooth muscle cells in vitro (abstract)

Wijnberg, M.J. (author), Nieuwenbroek, N.M.E. (author), Ouax, P.H.A. (author), Verheijen, J.H. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

The plasminogen activation system is known to be involved in several cell migration processes. A role for plasminogen activators in smooth muscle cell migration after vascular injury has been suggested from several animal studies. However, not much is known about their involvement in human vascular remodelling. In this study, the role of the...

article 1996

document

Coamatic® plasmin inhibitor: A new specific method for determination of plasmin inhibitor activity in plasma

Clason, S.B. (author), Meijef, P. (author), Kluft, C. (author), Ersdal, E. (author), Chromogenix AB, Mölndal, Sweden Gaubius Laboratory, TNO Preventie en Gezondheid (author)

It has recently been described that many commercial methods for the determination of plasmin inhibitor (PI) activity are not specific at low plasmin inhibitor concentrations (1, 2). This non-specificity results in values of 10-30 % when analysing PI-deficient plasmas. We have now developed a sensitive method which meets the criteria for a...

article 1996

document

Fibrinogen and atherosclerosis: A study in transgenic mice

Koopman, J. (author), Havekes, L. (author), Verheijen, J. (author), Gijbels, M. (author), Haverkate, F. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular disease as compared to the individual risk factors....

article 1996

document

Criteria for a specific plasmin inhibition test (SPIT) in human plasma

Meijer, P. (author), Kluft, C. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Test procedures of several commercially available functional test kits for α2-antiplasmin were investigated. The importance of the plasmin concentration, the amount of plasma used in the test and the preincubation time for a specific test for the determination of α2-antiplasmin were discussed. A Specific Plasmin Inhibition Test (SPIT) suitable...

article 1996

document

In vitro stabililty of a tissue-type plasminogen activator mutant, BM 06.022, in human plasma

Rijken, D.C. (author), Groeneveld, E. (author), Barrett-Bergshoeff, M.M. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

BM 06.022 is a non-glycosylated mutant of human tissue-type plasminogen activator (t-PA) comprising only the kringle-2 and proteinase domains. The in vivo half-life of BM 06.022 antigen is 4- to 5-fold longer than that of t-PA antigen. The in vitro half-life of the activity of BM 06.022 at therapeutic concentrations in plasma is shorter than...

article 1994

document

Sex steroids and lipoprotein metabolism

Gevers Leuven, J.A. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Lipoprotein metabolism is involved in atherogenesis. Female sex-hormones have substantial effects on both lipoprotein metabolism and the vessel wall. Cholesterol, one of the major lipids in lipoproteins, is both the substrate for, and the target of, the steroidal sex hormones.

article 1994

document

An improved method for the detection of α2-antiplasmin activity on the automated coagulation analyzer MLA Electra 1000C

Meijer, P. (author), Westerveld, W. (author), Huisman, L.G.M. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Comparison of the results for α2-antiplasmin activity of plasma samples (n = 61, range 0-125%) obtained by the 'immediate plasmin inhibition test' (IPIT) and by the automated method for the MLA Electra 1000C of Dade® shows a good correlation (R = 0.935) but a systematic disagreement especially relevant in the range below 40%. An improved method...

article 1994

document

Genistein reduces tumor necrosis factor α-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells

van Hinsbergh, V.W.M. (author), Vermeer, M. (author), Koolwijk, P. (author), Grimbergen, J. (author), Kooistra, T. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory...

article 1994

document

A bio-immuno assay to determine free tissue-type plasminogen activator (t-PA) in Stabilyte® plasma

Bos, R. (author), Revet, M. (author), Nieuwenhuizen, W. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

This article describes a two-step bio-immuno assay (BIA), which determines active (free) tissue-type plasminogen activator (t-PA) in (acidified) plasma. Plasma samples, diluted in buffer of pH 6.0, are added to the wells of a microtiter plate containing an immobilised monoclonal antibody which binds t-PA without affecting t-PA activity. After an...

article 1994