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Urokinase-type plasminogen activator system predicts risk of cardiovascular events in patients with angina pectoris: Results of the ECAPTURE study

de Maat, M.P.M. (author), Dooijewaard, G. (author), Meijer, P. (author), Binder, B.R. (author), Keber, D. (author), Risberg, B. (author), Kluft, C. (author), Jespersen, J. (author), Gaubius Instituut TNO (author)

In most Westernized societies cardiovascular diseases are the leading cause of death over the age of 45 years and one-quarter of these deaths occur in men below the age of 65 years. The haemostasis system has been identified as an important system in cardiovascular disease (CVD). The European Concerted Action on Prevention from Thrombosis by...

article 2001

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Markers of fibrinolytic potency and clotting activation in stable angina pectoris: Role of urokinase, assessment of atrioventricular differences and correlation with coronary patency

Páramo, U.A. (author), Panizo, C. (author), Montes, R. (author), Orbe, J. (author), Alegría, E. (author), Martínez-Caro, D. (author), Dooijewaard, G. (author), Gaubius instituut TNO (author)

To characterize the extent of activation of the hemostatic system and to detect local alterations which may favour thrombus formation we obtained samples from the right atrium (RA) and left ventricle (LV) of 60 stable angina patients (mean age 59 years, M/F: 49/11) during the cardiac catheterization procedure. None of the patients had a recent...

article 1999

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Alpha- and beta-adrenergic influences on the tissue and urokinase plasminogen activator systems

Larsson, P.T. (author), Wallén, N.H. (author), Wiman, B. (author), Dooijewaard, G. (author), Gaubius instituut TNO (author)

Objective: To study the influence of α- and β-adrenoceptor stimulation in vivo on fibrinolysis in healthy male volunteers. Design: Infusions were given in a single blind fashion and in a randomized order if placebo infusions were included. Setting: University Department (Karolinska Hospital). Subjects: Thirty-four healthy, non-smoking male...

article 1999

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Fibrinolytic properties of activated factor XII

Eam, B. (author), Dooijewaard, G. (author), Rijken, D.C. (author), Gaubius Instituut TNO (author)

Activated factor XII (FXIIa), the initiator of the contact activation system, has been shown to activate plasminogen in a purified system. However, the quantitative role of FXIIa as a plasminogen activator in (factor XH-dependent) fibrinolysis in plasma is still unclear. The aim of our study was to investigate plasminogen activator activity (PAA...

article 1998

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A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)

Braat, E.A.M. (author), Nauland, U. (author), Dooijewaard, G. (author), Rijken, P.C. (author), Gaubius Instituut TNO (author)

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA) for the assessment of tcu-PA/T in human body...

article 1996

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A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids

Braat, E.A.M. (author), Nauland, U. (author), Dooijewaard, G. (author), Rijken, D.C. (author), Gaubius Instituut TNO (author)

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA) for...

article 1996

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An amino acid polymorphism in histidine-rich glycoprotein (HRG) explains 59% of the variance in plasma HRG levels

Hennis, B.C. (author), Boomsma, D.I. (author), van Boheemen, P.A. (author), Engesser, L. (author), Kievit, P. (author), Dooijewaard, G. (author), Kluft, C. (author), TNO Preventie en Gezondheid (author)

A pedigree-based maximum likelihood method developed by Lange et al. (12) was used to study the contribution of a newly defined di-allelic polymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritability of 70%, an age effect of 3% and an effect of individual...

article 1995

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Identification and genetic analysis of a common molecular variant of histidine-rich glycoprotein with a difference of 2KD in apparent molecular weight

Hennis, B.C. (author), van Boheemen, P.A. (author), Wakabayashi, S. (author), Koide, T. (author), Hoffmann, J.J.M.L. (author), Kievit, P. (author), Dooijewaard, G. (author), Jansen, J.G. (author), Klutf, C. (author), TNO Preventie en Gezondheid (author)

Two forms of histidine-rich glycoprotein (HRG) were detected on SDS-PAGE by silver staining and immunoblotting after isolation of the protein from pooled plasma using immune-affinity chromatography followed by chromatography with heparin-Sepharose. Both forms were single-chain molecules and the apparent molecular weights of form 1 and form 2...

article 1995

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Protection of single-chain urokinase-type plasminogen activator (scu-PA) in aprotinin treated cardiac surgical patients undergoing cardiopulmonary bypass

Spannagl, M. (author), Dooijewaard, G. (author), Dietrich, W. (author), Kluft, C. (author), TNO Preventie en Gezondheid (author)

Intraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity during and after cardiopulmonary bypass (CPB)....

article 1995

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The acute-phase reaction of the fibrinolytic system in acute myocardial infarction and unstable angina

Six, A.J. (author), Liem, M.K. (author), Dooijewaard, G. (author), Brommer, E.J.P. (author), Haas, F. (author), Hollander-van Zalk, A. (author), de Bart, A.C.W. (author), van Hemel, N.M. (author), Kluft, C. (author), TNO Preventie en Gezondheid (author)

bookPart 1995

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Impaired fibrinolysis in the hemolytic-uremic syndrome of childhood

Menzel, D. (author), Levi, M. (author), Dooijewaard, G. (author), Peters, M. (author), ten Cate, J.W. (author), TNO Preventie en Gezondheid Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

article 1994

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The rationale of prevention of thrombosis by enhancing blood levels of single-chain urokinase-type plasminogen activator (scuPA)

Dooijewaard, G. (author), van Boheemen, P.A. (author), Binnema, D.J. (author), Kluft, C. (author), Gaubius Laboratory, VVO-TNO, PO Box 430, 2300 AK Leiden, Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

Chemicals/CAS: Tissue Plasminogen Activator, EC 3.4.21.68; Urinary Plasminogen Activator, EC 3.4.21.73

article 1992

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Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise

de Boer, A. (author), Kluft, C. (author), Dooijewaard, G. (author), Kasper, F.J. (author), Kroon, J.M. (author), Breimer, D.D. (author), Stiekema, J.C. (author), Cohen, A.F. (author)

The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran) (3,250 anti-Xa units i.v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized...

article 1992

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Impaired fibrinolysis in haemolytic uremic syndrome of childhood (abstract)

Menzel, D. (author), Levi, M. (author), Peters, M. (author), Dooijewaard, G. (author), Monnens, L. (author), ten Cate, J.W. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

article 1991

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Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma

Dooijewaard, G. (author), de Boer, A. (author), Turion, P.N.C. (author), Cohen, A.F. (author), Breimer, D.D. (author), Kluft, C. (author), Gaubius Instituut TNO (author)

The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA). Six healthy male volunteers (age 21-25 years) were screened...

article 1991

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An analysis of the activators of single-chain urokinase-type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction of normal plasma and of plasmas deficient in factor XII and prekallikrein

Binnema, D.J. (author), Dooijewaard, G. (author), Turion, P.N.C. (author), Gaubius Instituut TNO (author)

An analysis was made of the various possible activators of single-chain urokinase-type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction (DEF) of human plasma. scu-PA activators were detected in an assay system in which the substrate scu-PA, in physiological concentration (50 pM), was immuno-immobilized. After activation...

article 1991

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The contact-system dependent plasminogen activator from human plasma: Identification and characterization

Binnema, D.J. (author), Dooijewaard, G. (author), van Iersel, J.J.L. (author), Turion, P.N.C. (author), Kluft, C. (author), Gaubius Instituut TNO (author)

Apart from tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), a third PA appears to occur in human plasma. Its activity is initiated when appropriate triggers of the contact system are added, and the activation depends on the presence of factor XII and prekallikrein in plasma. The activity of this, so...

article 1990

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Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells

van Hinsbergh, V.W.M. (author), van den Berg, E.A. (author), Fiers, W. (author), Dooijewaard, G. (author), Gaubius Instituut TNO (author)

Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells, whereas they have no...

article 1990

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Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products

van Hinsbergh, V.W.M. (author), Bauer, K.A. (author), Kooistra, T. (author), Kluft, C. (author), Dooijewaard, G. (author), Sherman, M.L. (author), Nieuwenhuizen, W. (author), Gaubius instituut TNO (author)

Several investigators have reported that tumor necrosis factor (TNF) can alter the production of plasminogen activator type-1 (PAI-1) and plasminogen activators (PAs) by endothelial cells in vitro. We have examined the in vivo effects of recombinant human TNF administration on fibrinolysis as assessed by parameters in plasma during a 24-hour...

article 1990

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DDAVP induces systematic release of urokinase-type plasminogen activator

Levi, M. (author), ten Cate, J.W. (author), Dooijewaard, G. (author), Sturk, A. (author), Brommer, E.J. (author), Agnelli, G. (author), Gezondheidsorganisatie TNO Gaubius instituut TNO (author)

The desamino-d-arginine vasopressin (DDAVP) induced enhancement of endogenous fibrinolysis is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. The observation of concurrent release of urokinase-type plasminogen activator (u-PA), which eventually might cooperate in the enhanced fibrinolytic...

article 1989