document

A comparison of molecular technologies and genomotyping for tracing and strain characterization of Campylobacter isolates

van der Vossen, J. (author), Keijser, B. (author), Schuren, F. (author), Nocker, A. (author), Montijn, R. (author)

Thermophilic Campylobacter species are the most common cause of gastroenteritis in developed countries. Campylobacter spp. are ubiquitous in nature and widespread in livestock. Infections occur sporadically, and are believed to occur through consumption of contaminated meat products and from environmental sources. DNA-based techniques are...

conference paper 2011

document

Effect of neutralizing sera on factor X-mediated adenovirus serotype 5 gene transfer

Parker, A.L. (author), Waddington, S.N. (author), Buckley, S.M.K. (author), Custers, J. (author), Havenga, M.J.E. (author), van Rooijen, N. (author), Goudsmit, J. (author), McVey, J.H. (author), Nicklin, S.A. (author), Baker, A.H. (author), TNO Kwaliteit van Leven (author)

The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based...

article 2009

document

Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo

de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...

article 2008

document

The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI

TNO Kwaliteit van Leven (author), Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)

LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...

article 2008

document

ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency

TNO Kwaliteit van Leven (author), Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)

Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...

article 2008

document

The effect of interleukin-10 knock-out and overexpression on neointima formation in hypercholesterolemic APOE*3-Leiden mice

Eefting, D. (author), Schepers, A. (author), de Vries, M.R. (author), Pires, N.M.M. (author), Grimbergen, J.M. (author), Lagerweij, T. (author), Nagelkerken, L.M. (author), Monraats, P.S. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

Objective: Inflammatory factors are thought to play a regulatory role in restenosis. Interleukin-10 (IL10) is an important anti-inflammatory cytokine with anti-atherogenic potentials. The aim of this study was to assess the effects of IL10 modulation on cuff-induced neointima formation in hypercholesterolemic APOE*3-Leiden mice. Methods: The...

article 2007

document

Prolonged in vivo gene silencing by electroporation-mediated plasmid delivery of small interfering RNA

Eefting, D. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), van Weel, V. (author), Kaijzel, E.L. (author), Que, I. (author), Moon, R.T. (author), Löwik, C.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

For the successful application of RNA interference in vivo, it is desired to achieve (local) delivery of small interfering RNAs (siRNAs) and long-term gene silencing. Nonviral electrodelivery is suitable to obtain local and prolonged expression of transgenes. By intramuscular electrodelivery of a plasmid in which two opposing human polymerase...

article 2007

document

Insertion sequence-driven diversification creates a globally dispersed emerging multiresistant subspecies of E. faecium

TNO Kwaliteit van Leven TNO Voeding (author), Leavis, H.L. (author), Willems, R.J.L. (author), van Wamel, W.J.B. (author), Schuren, F.H. (author), Caspers, M.P.M. (author), Bonten, M.J.M. (author)

Enterococcus faecium, an ubiquous colonizer of humans and animals, has evolved in the last 15 years from an avirulent commensal to the third most frequently isolated nosocomial pathogen among intensive care unit patients in the United States. E. faecium combines multidrug resistance with the potential of horizontal resistance gene transfer to...

article 2007

document

Tissue inhibitor of metalloproteinase-3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo without affecting antitumor efficacy in malignant glioma

Lamfers, M.L.M. (author), Gianni, D. (author), Tung, C.H. (author), Idema, S. (author), Schagen, F.H.E. (author), Carette, J.E. (author), Quax, P.H.A. (author), van Beusechem, V.W. (author), van der Top, W.P. (author), Dirven, C.M.F. (author), Chiocca, E.A. (author), Gerritsen, W.R. (author), TNO Kwaliteit van Leven (author)

Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To...

article 2005

document

ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression

TNO Kwaliteit van Leven (author), Gerritsen, G. (author), Rensen, P.C.N. (author), Kypreos, K.E. (author), Zannis, V.I. (author), Havekes, L.M. (author), van Dijk, K.W. (author)

Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by...

article 2005

document

Generation of a recombinant apolipoprotein E variant with improved biological functions: Hydrophobic residues (LEU-261, TRP-264, PHE-265, LEU-268, VAL-269) of apoE can account for the apoE-induced hypertriglyceridemia

TNO Kwaliteit van Leven (author), Kypreos, K.E. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Zannis, V.I. (author)

To identify the residues in the carboxyl-terminal region 260-299 of human apolipoprotein E (apoE) that contribute to hypertriglyceridemia, two sets of conserved, hydrophobic amino acids between residues 261 and 283 were mutated to alanines, and recombinant adenoviruses expressing these apoE mutants were generated. Adenovirus-mediated gene...

article 2005

document

The Aspergillus nidulans amdS gene as a marker for the identification of multicopy T-DNA integration events in Agrobacterium-mediated transformation of Aspergillus awamori

Michielse, C.B. (author), Ram, A.F.J. (author), van den Hondel, C.A.M.J.J. (author), TNO Voeding (author)

The Aspergillus nidulans amdS selection marker was used for the identification of multicopy T-DNA insertions in Agrobacterium-mediated transformation of Asp. awamori. The selection of transformants on agar plates containing acetamide as sole nitrogen source and hygromycin resulted in a six-fold decrease in the transformation frequency, compared...

article 2004

document

The relevance of gene transfer to the safety of food and feed derived from genetically modified (GM) plants

van den Eede, G. (author), Aarts, H. (author), Buhk, H.J. (author), Corthier, G. (author), Flint, H.J. (author), Hammes, W. (author), Jacobsen, B. (author), Midtvedt, T. (author), van der Vossen, J. (author), von Wright, A. (author), Wackernagel, W. (author), Wilcks, A. (author), TNO Voeding (author)

In 2000, the thematic network ENTRANSFOOD was launched to assess four different topics that are all related to the testing or assessment of food containing or produced from genetically modified organisms (GMOs). Each of the topics was linked to a European Commission (EC)-funded large shared cost action (see http://www.entransfood.com). Since the...

article 2004

document

ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglycerides (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis

TNO Preventie en Gezondheid (author), Schaap, F.G. (author), Rensen, P.C.N. (author), Voshol, P.J. (author), Vrins, C. (author), van der Vliet, H.N. (author), Chamuleau, R.A.F.M. (author), Havekes, L.M. (author), Groen, A.K. (author), van Dijk, K.W. (author)

ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 108 plaque-forming units/mouse) dose...

article 2004

document

TR3 orphan receptor is expressed in vascular endothelial cells and mediates cell cycle arrest

Arkenbout, E.K. (author), van Bragt, M. (author), Eldering, E. (author), van Bree, C. (author), Grimbergen, J.M. (author), Quax, P.H.A. (author), Pannekoek, H. (author), de Vries, C.J.M. (author), Gaubius Instituut TNO (author)

Objective - Endothelial cells play a pivotal role in vascular homeostasis. In this study, we investigated the function of the nerve growth factor-induced protein-B (NGFI-B) subfamily of nuclear receptors comprising the TR3 orphan receptor (TR3), mitogen-induced nuclear orphan receptor (MINOR), and nuclear orphan receptor of T cells (NOT) in...

article 2003

document

Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: Efficient human cell infection and bypass of preexisting adenovirus immunity

Vogels, R. (author), Zuijdgeest, D. (author), van Rijnsoever, R. (author), Hartkoorn, E. (author), Damen, I. (author), de Béthune, M.-P. (author), Kostense, S. (author), Penders, G. (author), Helmus, N. (author), Koudstaal, W. (author), Cecchini, M. (author), Wetterwald, A. (author), Sprangers, M. (author), Lemckert, A. (author), Ophorst, O. (author), Koel, B. (author), van Meerendonk, M. (author), Quax, P. (author), Panitti, L. (author), Grimbergen, J. (author), Bout, A. (author), Goudsmit, J. (author), Havenga, M. (author)

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the...

article 2003

document

Gene transfer of the urokinase-type plasminogen activator receptor-targeted matrix metalloproteinase inhibitor TIMP-1.ATF suppresses neointima formation more efficiently than tissue inhibitor of metalloproteinase-1

Lamfers, M.L.M. (author), Grimbergen, J.M. (author), Aalders, M.C. (author), Havenga, M.J. (author), de Vries, M.R. (author), Huisman, L.G.M. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius instituut TNO (author)

Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit both protease systems...

article 2002

document

Adenovirus-mediated transfer of the 39 kD receptor-associated protein increases fibrinolytic capacity

Goedde, M.F. (author), Grimbergen, J.M. (author), Toet, K.H. (author), Sitter, T. (author), Quax, P.H. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Background. The mesothelium has an important role in maintaining an adequate fibrinolytic capacity in the peritoneal cavity and thus in preventing the formation of fibrinous peritoneal adhesions by secreting the fibrinolytic enzyme tissue-type plasminogen activator (t-PA). The fibrinolytic activity of human mesothelial cells (HMCs) is...

article 2001

document

In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI

Lamfers, M.L.M. (author), Lardenoye, J.H.P. (author), de Vries, M.R. (author), Aalders, M.C. (author), Engelse, M.A. (author), Grimbergen, J.M. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius Instituut TNO (author)

Injury-induced neointimal development results from migration and proliferation of vascular smooth muscle cells (SMC). Cell migration requires controlled proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is a major contributor to this process by degrading various matrix proteins directly, or indirectly by activating...

article 2001

document

Apolipoprotein E2 (Lys146→Gln) causes hypertriglyceridemia due to an apolipoprotein E variant-specific inhibition of lipolysis of very low density lipoproteins-triglycerides

de Beer, F. (author), van Dijk, K.W. (author), Jong, M.C. (author), van Vark, L.C. (author), van der Zee, A. (author), Hofker, M.H. (author), Fallaux, F.J. (author), Hoeben, R.C. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

The apolipoprotein E2 (Lys146→Gln) variant is associated with a dominant form of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E (apoE). It was hypothesized that the high amounts of triglycerides in the very low density lipoprotein (VLDL)...

article 2000