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Verbeek, R. (author), van der Mark, K. (author), Wawrousek, E.F. (author), Plomp, A.C. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire...article 2007
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Meesters, R.J.W. (author), van Eijk, H.M.H. (author), ten Have, G.A.M. (author), de Graaf, A.A. (author), Venema, K. (author), van Rossum, B.E.J. (author), Deutz, N.E.P. (author), TNO Kwaliteit van Leven (author)A new method involving zinc sulphate deproteinization was developed to study short chain fatty acids (SCFA) production in the colon and subsequent occurrence of SCFA in blood. SCFA were baseline separated in a 30 min cycle using ion-exclusion chromatography and detected by mass spectrometry. Concentrations could be measured down to 10 μM and...article 2007
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van Bezooijen, R.L. (author), Svensson, J.P. (author), Eefting, D. (author), Visser, A. (author), van der Horst, G. (author), Karperien, M. (author), Quax, P.H.A. (author), Vrieling, H. (author), Papapoulos, S.E. (author), ten Dijke, P. (author), Löwik, W.G.M.C. (author), TNO Kwaliteit van Leven (author)Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family...article 2007
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Maas, W.J. (author), van Herwijnen, M. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with...article 2007
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Mulder, M. (author), Koopmans, G. (author), Wassink, G. (author), Mansouri, G.A. (author), Simard, M.-L. (author), Havekes, L.M. (author), Prickaerts, J. (author), Blokland, A. (author), TNO Kwaliteit van Leven (author)An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired...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), van der Hoogt, C.C. (author), de Haan, W. (author), Westerterp, M. (author), Hoekstra, M. (author), Dallinga-Thie, G.M. (author), Romijn, J.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)In addition to efficiently decreasing VLDL-triglycerides (TGs), fenofibrate increases HDL-cholesterol levels in humans. We investigated whether the fenofibrate-induced increase in HDL-cholesterol is dependent on the expression of the cholesteryl ester transfer protein (CETP). To this end, APOE*3-Leiden (E3L) transgenic mice without and with the...article 2007
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TNO Kwaliteit van Leven (author), Gautier, T. (author), Tietge, U.J.F. (author), Boverhof, R. (author), Perton, F.G. (author), Le Guern, N. (author), Masson, D. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Lagrost, L. (author), Kuipers, F. (author)The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (...article 2007
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TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Pires, N.M.M. (author), van Mierlo, G.J.D. (author), Kleemann, R. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...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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TNO Kwaliteit van Leven (author), Hassane, S. (author), Claij, N. (author), Lantinga-van Leeuwen, I.S. (author), van Munsteren, J.C. (author), van Lent, N. (author), Hanemaaijer, R. (author), Breuning, M.H. (author), Peters, D.J.M. (author), de Ruiter, M.C. (author)OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in...article 2007
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TNO Kwaliteit van Leven (author), Moen, C.J.A. (author), Tholens, A.P. (author), Voshol, P.J. (author), de Haan, W. (author), Havekes, L.M. (author), Gargalovic, P. (author), Lusis, A.J. (author), van Dyk, K.W. (author), Frants, R.R. (author), Hofker, M.H. (author), Rensen, P.C.N. (author)The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on the BALB/cJ background. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hypertriglyceridemia....article 2007
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TNO Kwaliteit van Leven (author), Pires, N.M.M. (author), Pols, T.W.H. (author), de Vries, M.R. (author), Tiel, C.M.van (author), Bonta, P.I. (author), Vos, M. (author), Arkenbout, E.K. (author), Pannekoek, H. (author), Jukema, J.W. (author), Quax, P.H.A. (author), de Vries, C.J.M. (author)BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...article 2007
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...article 2006
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Zadelaar, A.S.M. (author), Boesten, L.S.M. (author), Pires, N.M.M. (author), van Nieuwkoop, A. (author), Biessen, E.A.L. (author), Jukema, W. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Here we describe a means to conditionally modify genes at a predefined and localized region of the vasculature using a perivascular drug delivery device (PDD). A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre...article 2006
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Fiehn, O. (author), Kristal, B. (author), van Ommen, B. (author), Sumner, L.W. (author), Sansone, S.-A. (author), Taylor, C. (author), Hardy, N. (author), Kaddurah-Daouk, R. (author), TNO Kwaliteit van Leven (author)Metabolite concentrations in cellular systems are very much dependent on the physiological, environmental, and genetic status of an organism and are regarded as the ultimate result of cellular regulation, resulting in the visible phenotypes. Therefore, the comprehensive analysis of metabolite levels and fluxes renders a suitable tool for...article 2006
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Marco, M.L. (author), Pavan, S. (author), Kleerebezem, M. (author), TNO Kwaliteit van Leven (author)The possibility that certain microorganisms might be beneficial to human health is highlighted by the numerous consumer products containing probiotic bacteria. Probiotics are typically administered in food that, following entry into the gastro-intestinal tract, results in measurable health-promoting effects. Although there is a growing list of...article 2006
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Pires, N.M.M. (author), Jukema, J.W. (author), Daemen, M.J.A.P. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical...article 2006