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TNO Kwaliteit van Leven (author), Heijboer, A.C. (author), Donga, E. (author), Voshol, P.J. (author), Dang, Z.C. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author)Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA...article 2005
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TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Verloop, R.E. (author), Pulskens, W.P.C. (author), Velema, E. (author), Grimbergen, J.M. (author), Quax, P.H. (author), Goumans, M.J. (author), Pasterkamp, G. (author), Kleijn, D.P.V.de (author)Background: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been...article 2005
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TNO Kwaliteit van Leven (author), Verschuur, M. (author), Jong, M.de (author), Felida, L. (author), Maat, M.P.M.de (author), Vos, H.L. (author)An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation...article 2005
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TNO Kwaliteit van Leven (author), Duivenvoorden, I. (author), Teusink, B. (author), Rensen, P.C.N. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author)Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely...article 2005
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TNO Kwaliteit van Leven (author), Monraats, P.S. (author), Rana, J.S. (author), Nierman, M.C. (author), Pires, N.M.M. (author), Zwinderman, A.H. (author), Kastelein, J.J.P. (author), Kuivenhoven, J.A. (author), de Maat, M.P.M. (author), Rittersma, S.Z.H. (author), Schepers, A. (author), Doevendans, P.A.F. (author), de Winter, R.J. (author), Tio, R.A. (author), Frants, R.R. (author), Quax, P.H.A. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author)OBJECTIVES: We sought to identify polymorphisms in genes that predispose to restenosis. BACKGROUND: Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined...article 2005
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Clish, C.B. (author), Davidov, E. (author), Oresic, M. (author), Plasterer, T.N. (author), Lavine, G. (author), Londo, T. (author), Meys, M. (author), Snell, P. (author), Stochaj, W. (author), Adourian, A. (author), Zhang, X. (author), Morel, N. (author), Neumann, E. (author), Verheij, E. (author), Vogels, J.T.W.E. (author), Havekes, L.M. (author), Afeyan, N. (author), Regnier, F. (author), van der Greef, J. (author), Naylor, S. (author), TNO Preventie en Gezondheid (author)Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden ...article 2004
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van Weel, V. (author), Deckers, M.M.L. (author), Grimbergen, J.M. (author), van Leuven, K.J.M. (author), Lardenoye, J.W.H.P. (author), Schlingemann, R.O. (author), van Nieuw Amerongen, G.P. (author), van Bockel, J.H. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius Instituut TNO (author)Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization, as evaluated by angiography...article 2004
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Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)Objective-Cholesterol 7α-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. Methods and Results-Female mice received a chow or...article 2004
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Lindeman, J.H.N. (author), Hanemaaijer, R. (author), Mulder, A. (author), Dijkstra, P.D.S. (author), Szuhai, K. (author), Bromme, D. (author), Verheijen, J.H. (author), Hogendoorn, P.C.W. (author)Giant cell tumor (GCT) of bone is a neoplasm of bone characterized by a localized osteolytic lesion. The nature of GCT is an enigma and the cell type(s) and protease(s) responsible for the extensive localized clinicoradiological osteolysis remain unresolved. We evaluated protease expression and cellular distribution of the proteolytic machinery...article 2004
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Hollestelle, S.C.G. (author), de Vries, M.R. (author), van Keulen, J.K. (author), Schoneveld, A.H. (author), Vink, A. (author), Strijder, C.F. (author), van Middelaar, B.J. (author), Pasterkamp, G. (author), Q́uax, P.H.A. (author), de Kleijn, D.P.V. (author), TNO Preventie en Gezondheid (author)Background-Toll-like receptor 4 (Tlr4) is the receptor for exogenous lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in arthritic and oncological specimens in which matrix turnover is an important feature. In atherosclerosis, outward remodeling...article 2004
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Plaisier, M. (author), Kapiteijn, K. (author), Koolwijk, P. (author), Fijten, C. (author), Hanemaaijer, R. (author), Grimbergen, J.M. (author), Mulder-Stapel, A. (author), Quax, P.H.A. (author), Helmerhorst, F.M. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)In the endometrium, angiogenesis is a physiological process, whereas in most adult tissues neovascularization is initiated only during tissue repair or pathological conditions. Pericellular proteolysis plays an important role in angiogenesis being required for endothelial cell migration, invasion, and tube formation. We studied the expression of...article 2004
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Heijne, W.H.M. (author), Slitt, A.L. (author), van Bladeren, P.J. (author), Groten, J.P. (author), Klaassen, C.D. (author), Stierum, R.H. (author), van Ommen, B. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while...article 2004
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Price, R.J. (author), Scott, M.P. (author), Walters, D.G. (author), Stierum, R.H. (author), Groten, J.P. (author), Meredith, C. (author), Lake, B.G. (author), TNO Voeding (author)The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets containing 1457 and 10,155 ppm butylated...article 2004
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TNO Preventie en Gezondheid (author), Mandard, S. (author), Zandbergen, F. (author), Nguan, S.T. (author), Escher, P. (author), Patsouris, D. (author), Koenig, W. (author), Kleemann, R. (author), Bakker, A. (author), Veenman, F. (author), Wahli, W. (author), Müller, M. (author), Kersten, S. (author)The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was previously identified as a novel adipocytokine that was up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. To further characterize FIAF, we studied regulation of FIAF mRNA and protein in liver and adipose cell lines as well as in...article 2004
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TNO Preventie en Gezondheid (author), Ha-Vinh, R. (author), Alanay, Y. (author), Bank, R.A. (author), Campos-Xavier, A.B. (author), Zankl, A. (author), Superti-Furga, A. (author), Bonafé, L. (author)Bruck syndrome (BS) is a recessively-inherited phenotypic disorder featuring the unusual combination of skeletal changes resembling osteogenesis imperfects (OI) with congenital contractures of the large joints. Clinical heterogeneity is apparent in cases reported thus far. While the genes coding for collagen 1 chains are unaffected in BS, there...article 2004
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Lu, K.Q. (author), Brenneman, S. (author), Burns Jr., R. (author), Vink, A. (author), Gaines, E. (author), Haake, A. (author), Gaspari, A. (author)Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-α) production by monocytes. However, its mechanism of action in the skin is not known....article 2003
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Beauchamp, N.J. (author), van Achterberg, T.A.E. (author), Engelse, M.A. (author), Pannekoek, H. (author), de Vries, C.J.M. (author), Gaubius Instituut TNO (author)Migration and proliferation of vascular smooth muscle cells (SMCs) are key events in atherosclerosis. However, little is known about alterations in gene expression upon transition of the quiescent, contractile SMC to the proliferative SMC. We performed serial analysis of gene expression (SAGE) of cultured, human SMCs, either grown under resting...article 2003
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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
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Lopatinskaya, L. (author), Boxel van-Dezaire, A.H.H. (author), Barkhof, F. (author), Polman, C.H. (author), Lucas, C.J. (author), Nagelkerken, L. (author)In this longitudinal study, we examined the expression of Fas, FasL, CCR3, CCR5 and CXCR3 mRNA in peripheral blood mononuclear cells (PBMCs) of secondary progressive (SP) and relapsing-remitting (RR) multiple sclerosis (MS) patients. In RR patients, FasL, CCR3 and CCR5 mRNA levels were increased prior to the exacerbations, but these decreased...article 2003
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Heijne, W.H.M. (author), Stierum, R.H. (author), Slijper, M. (author), van Bladeren, P.J. (author), van Ommen, B. (author)Toxicogenomics is a novel approach integrating the expression analysis of thousands of genes (transcriptomics) or proteins (proteomics) with classical methods in toxicology. Effects at the molecular level are related to pathophysiological changes of the organisms, enabling detailed comparison of mechanisms and early detection and prediction of...article 2003