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van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)
Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...
article 2009
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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...
article 2009
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Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)
Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...
article 2009
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Kersten, S. (author), Lichtenstein, L. (author), Steenbergen, E. (author), Mudde, K. (author), Hendriks, H.F.J. (author), Hesselink, M.K. (author), Schrauwen, P. (author), Müller, M. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human....
article 2009
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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)
This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...
article 2008
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Groux-Degroote, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), Neumann, S. (author), Theos, A.C. (author), de Mazière, A.M. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)
Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1)...
article 2008
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Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)
Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...
article 2008
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Fabriek, B.O. (author), Møller, H.J. (author), Vloet, R.P.M. (author), van Winsen, L.M. (author), Hanemaaijer, R. (author), Teunissen, C.E. (author), Uitdehaag, B.M.J. (author), van den Berg, T.K. (author), Dijkstra, C.D. (author), TNO Kwaliteit van Leven (author)
The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present...
article 2007
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Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)
As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...
article 2007
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Halter, D. (author), Neumann, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), de Mazière, A.M. (author), Vieira, O.V. (author), Mattjus, P. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)
Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate...
article 2007
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van Zanden, J.J. (author), van der Woude, H. (author), Vaessen, J. (author), Usta, M. (author), Wortelboer, H.M. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3′-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4...
article 2007
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Lammers, J.H.C.M. (author), Emmen, H.H. (author), Muijser, H. (author), Hoogendijk, E.M.G. (author), McKee, R.H. (author), Owen, D.E. (author), Kulig, B.M. (author), TNO Kwaliteit van Leven (author)
To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in...
article 2007
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Ferreira, V. (author), van Dijk, K.W. (author), Groen, A.K. (author), Vos, R.M. (author), van der Kaa, J. (author), Gijbels, M.J.J. (author), Havekes, L.M. (author), Pannekoek, H. (author), TNO Kwaliteit van Leven (author)
Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor κB (NF-κB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-κB activation is specifically inhibited in macrophages by overexpressing...
article 2007
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Bsibsi, M. (author), Bajramovic, J.J. (author), van Duijvenvoorden, E. (author), Persoon, C. (author), Ravid, R. (author), van Noort, J.M. (author), Vogt, M.H.J. (author), TNO Kwaliteit van Leven (author)
Human astrocytes express a limited repertoire of Toll-like receptor (TLR) family members including TLR1-4, which are expressed on the cell surface. Also, TLR3 but not TLR4 activation on astrocytes induces expression of several factors involved in neuroprotection and down-regulation of inflammation rather than in the onset of traditional pro...
article 2007
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Ousman, S.S. (author), Tomooka, B.H. (author), van Noort, J.M. (author), Wawrousek, E.F. (author), O'Conner, K. (author), Hafler, D.A. (author), Sobel, R.A. (author), Robinson, W.H. (author), Steinman, L. (author), TNO Kwaliteit van Leven (author)
αB-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has anti-apoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain. The...
article 2007
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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
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TNO Kwaliteit van Leven (author), Alkemade, F.E. (author), de Gittenberger-Groot, A.C. (author), Schiel, A.E. (author), van Munsteren, J.C. (author), Hogers, B. (author), van Vliet, L.S.J. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), de Ruiter, M.C. (author)
OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of...
article 2007
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McKee, R.H. (author), Lammers, J.H.C.M. (author), Hoogendijk, E.M.G. (author), Emmen, H.H. (author), Muijser, H. (author), Barsotti, D.A. (author), Owen, D.E. (author), Kulig, B.M. (author), TNO Kwaliteit van Leven (author)
As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to...
article 2006
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Parnham, M.J. (author), Bogaards, J.J.P. (author), Schrander, F. (author), Schut, M.W. (author), Orešković, K. (author), Mildner, B. (author), TNO Kwaliteit van Leven (author)
PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with S9 fractions and NADPH was determined by HPLC,...
article 2005
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Portengen, L. (author), Preller, L. (author), Tielen, M. (author), Doekes, G. (author), Heederik, D. (author), TNO Kwaliteit van Leven (author)
Background: Recent studies have reported a low prevalence of atopic sensitization and respiratory allergy in children growing up on farms. Objectives: We sought to evaluate the dose-response relationship between endotoxin and atopic sensitization in adult farmers and to assess the effect on respiratory health outcomes. Methods: Data on endotoxin...
article 2005
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