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Jespersen, S. (author), Ploemen, J.H.T.M. (author), Bladeren, P.J. (author), Niessen, W.M.A. (author), Tjaden, U.R. (author), van der Greef, J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)A mass spectrometric method providing qualitative site-specific information regarding covalent modification of proteins is described. The method involves comparison of unmodified and modified proteins by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) peptide mapping in combination with site-specific mutagenesis of...article 1996
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Arts, J. (author), Grimbergen, J. (author), Bosma, P.J. (author), Rahmsdorf, H.J. (author), Kooistra, T. (author), Gaubius Laboratory, TNO-PG, Leiden, Netherlands Institut für Genetik, Forschungszentrum Karlsruhe, Germany TNO Preventie en Gezondheid (author)Experiments were designed to clarify the role of c-Jun/c-Fos and of putative phorbol 12-myristate-13-acetate-(PMA)-responsive elements (TREs) in the induction of plasminogen-activator inhibitor 1 (PAI-1) gene transcription in the human hepatoma cell line HepG2 by activators of protein kinase C (PKC). Treatment of HepG2 cells with the phorbol...article 1996
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Haddeland, U. (author), Sletten, K. (author), Bennick, A. (author), Nieuwenhuizen, W. (author), Brosstad, F. (author), Gaubius Instituut TNO (author)The present paper shows that conformationally changed fibrinogen can expose the sites Aα-(148-160) and γ-(312-324) involved in stimulation of the tissue-type plasminogen activator (t-PA)-catalysed plasminogen activation. The exposure of the stimulating sites was determined by ELISA using mABs directed to these sites, and was shown to coincide...article 1996
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Kuiper, J. (author), van 't Hof, A. (author), Otter, M. (author), Biessen, E.A.L. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratory, P. O. Box 9503, 2300 RA Leiden, Netherlands Gaubius Laboratory, TNO Prevention and Health, P.O. Box 430, 2300 AK Leiden, Netherlands (author)The fibrin-specific thrombolyticum tissue-type plasminogen activator (t-PA) has proven to be a potent drug in several clinical trials, but its clinical application is complicated by the rapid clearance of t-PA from the circulation. The rapid plasma clearance of t-PA results from the uptake of t-PA in the liver. t-PA consists of several domains...article 1996
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van Setten, P.A. (author), Monnens, L.A.H. (author), Verstraten, R.G.G. (author), van den Heuvel, L.P.W.J. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)The epidemic form of the hemolytic uremic syndrome (HUS) has been associated with a verocytotoxin producing Escherichia coli infection. Endothelial cell damage of glomeruli and arterioles of the kidney plays a central role in the pathogenesis of HUS. A number of observations in vivo and in vitro indicate that inflammatory mediators contribute to...article 1996
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TNO Preventie en Gezondheid Gaubius Instituut TNO (author), Biessen, E.A.L. (author), Noorman, F. (author), van Teijlingen, M.E. (author), Kuiper, J. (author), Barrett-Bergshoeff, M.M. (author), Bijsterbosch, M.K. (author), Rijken, D.G. (author), van Berkel, T.J.G. (author)In search of synthetic high affinity ligands for the mannose receptor, we synthesized a series of lysine-based oligomannosides containing two (M2L) to six (M6L5) terminal alpha-D-mannose groups that are connected with the backbone by flexible elongated spacers (16 Å). The synthesized cluster mannosides were all able to displace binding of...article 1996
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Gaubius Instituut TNO (author), Bakker, A.H.F. (author), Weening-Verhoeff, E.J.D. (author), Verheijen, J.H. (author)To describe the role of the lysyl binding site in the interaction of tissue-type plasminogen activator (t-PA, FGK1K2P) with a forming fibrin clot, we performed binding experiments with domain deletion mutants GK1K2P, K2P, and the corresponding point mutants lacking the lysyl binding site in the absence and the presence of ε-amino caproic acid ...article 1995
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Lang, M.S. (author), Oostendorp, R.A.J. (author), Simons, P.J. (author), Boersma, W. (author), Knegt, P. (author), van Ewijk, W. (author)Both retroviral infections as well as human tumors may cause immunosuppression. One of the factors involved in immunosuppression in patients with squamous cell carcinoma of the head and neck (SCC-HN) is a protein related in the retroviral protein p15E. A conserved, 17-amino acid sequence represents the immunosuppressive epitope of retroviral...article 1994
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Gaubius Instituut TNO (author), Bakker, A.H.F. (author), van der Greef, W. (author), Rehberg, E.F. (author), Marotti, K.R. (author), Verheijen, J.H. (author)Despite the high overall similarity in primary structure between kringle one (K1) and kringle two (K2) of tissue-type plasminogen activator (t-PA) there exists an enormous functional difference. It is thought that, in contrast to K1, K2 mediates lysine binding and fibrin binding and is involved in stimulation of plasminogen activation by fibrin...article 1993
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Wang, M. (author), Sedee, N.J.A. (author), Heidekamp, F. (author), Snaar-Jagalska, B.E. (author)We report the existence of several families of GTP-binding proteins in barley aleurone protoplasts. Partial purified plasma membrane proteins were separated by SDS-PAGE, transferred to a nitrocellulose filter and incubated with either antisera raised against a highly conserved animal G protein alpha subunit peptide/or Ras protein, or with [alpha...article 1993
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van Eijsden, R.R. (author), Hoedemaeker, F.J. (author), Díaz, C.L. (author), Lugtenberg, B.J.J. (author), de Sylvia Pater, B. (author), Kijne, J.W. (author)As part of a strategy to determine the precise role of pea (Pisum sativum) lectin, Psl, in nodulation of pea by Rhizobium leguminosarum, mutations were introduced into the genetic determinant for pea lectin by site-directed mutagenesis using PCR. Introduction of a specific mutation, N125D, into a central area of the sugar-binding site resulted...article 1992
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Instituut voor verouderings- en vaatziekten onderzoek TNO (author), Yonekawa, O. (author), Voskuilen, M. (author), Nieuwenhuizen, W. (author)In previous publications [e.g. Voskuilen, Vermond, Veeneman, Van Boom, Klasen, Zegers and Nieuwenhuizen (1987) J. Biol. Chem. 262, 5944-5946] we have shown that fibrin(ogen) chain fragment Aα-(148-160) contains a site that contributes to the acceleration of Glu-plasminogen activation by tissue-type plasminogen activator (t-PA). In contrast with...article 1992
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Otter, M. (author), Kuiper, J. (author), Bos, R. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Gaubius Laboratory Instituut voor verouderings- en vaatziekten onderzoek TNO (author)The interaction of 125I-labelled tissue-type plasminogen activator (125I-t-PA) with freshly isolated rat parenchymal and endothelial liver cells was studied. Binding experiments at 4°C with parenchymal cells and endothelial liver cells indicated the presence of 68000 and 44000 high-affinity t-PA-binding sites, with an apparent K(d) of 3.5 and 4...article 1992
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van Raaij, J.A.G.M. (author), van den Berg, K.J. (author), Notten, W.R.F. (author), Medisch Biologisch Laboratorium TNO (author)Previous results have indicated that hexachlorobenzene (HCB)-induced hypothyroidism may be caused by its main metabolite pentachlorophenol (PCP), and by tetrachlorohydroquinone (TCHQ), rather than by the parent compound. In the present experiments it was investigated whether hormone displacement from serum carriers could be a factor in the...article 1991
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Instituut CIVO-Toxicologie en Voeding TNO (author), van Ommen, B. (author), Ploemen, J.H.T.M. (author), Bogaards, J.J.P. (author), Monks, T.J. (author), Gau, S.S. (author), van Bladeren, P.J. (author)The irreversible inhibition of the rat glutathione S-transferase (GST) isoenzyme 1-1 by a series of halogenated 1,4-benzoquinones and their GSH conjugates was studied quantitatively by analysing the time course of enzyme inactivation. With increasing numbers of chlorine substituents, the rate of inhibition greatly increased. Incorporation of a...article 1991
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Rijken, D.C. (author), Groeneveld, E. (author), Gaubius Instituut TNO (author)Recent studies suggest that plasminogen activators not only hydrolyse a specific arginine-valine bond in plasminogen, but may also cleave other proteins such as fibronectin. We studied the substrate specificity, particularly the preference for arginyl over lysyl peptide bonds, of tissue-type plasminogen activator (t-PA) as well as of two-chain...article 1991
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Medisch Biologisch Laboratorium TNO (author), van den Berg, K.J. (author)Previous results (Brouwer and van den Berg, Toxicol. Appl. Pharmacol., 85 (1986) 301) indicated preferential binding of a hydroxylated metabolite of tetrachlorobiphenyl to transthyretin (TTR) a carrier of thyroxine (T4). In the present study it was investigated whether the T4 binding site of TTR could be occupied specifically by hydroxylated...article 1990
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Wasser, M.N.J.M. (author), Koppert, P.W. (author), Arndt, J.W. (author), Emeis, J.J. (author), Feitsma, R.I.J. (author), Pauwels, E.K.J. (author), Nieuwenhuizen, W. (author), Gaubius Instituut TNO (author)Balb/c mice were immunized with human plasmin-generated fibrinogen degradation product Y. Spleen cells were fused with P3X63-Ag8.653 myeloma cells. A clone (Y22) was found that produces monoclonal antibodies (MoAbs) with a strong reactivity with human fibrin and only a weak reactivity with fibrinogen in an enzyme immunoassay (EIA). Y22 also...article 1989
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Gaubius instituut TNO (author), Rijken, D.C. (author), Emeis, J.J. (author)In order to assess which part of the tissue-type plasminogen activator (t-PA) molecule should be (genetically) modified to obtain more-slowly-clearing mutants, two-chain t-PA and its isolated heavy and light chains were radiolabelled and injected into rats. The vast majority of t-PA and the heavy chain disappeared from the blood circulation with...article 1986
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TNO Gaubius Institute for Cardiovascular Research, 2313 AD Leiden, Netherlands (author), Rijken, D.C. (author), Groeneveld, E. (author)Two-chain tissue-type plasminogen activator (t-PA), which consists of a heavy chain (M(r) ??? 38,000) and a light chain (M(r) ??? 31,000) connected by a disulfide bridge, was reduced with 2-mercaptoethanol and then air-reoxidized at a low protein concentration and carboxamidomethylated. The two chains were separated by means of zinc chelate...article 1986