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Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers

van Doorn, M. (author), Vogels, J. (author), Tas, A. (author), van Hoogdalem, E.J. (author), Burggraaf, J. (author), Cohen, A. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

Aims: To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the differences in metabolite concentrations between T2DM...

article 2007

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Sensitivity of 1H NMR analysis of rat urine in relation to toxicometabonomics. Part I: Dose-dependent toxic fffects of Bromobenzene and paracetamol

Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.P.H.T.M. (author), Horbach, G.J. (author), Smit, M.J. (author), Zandberg, P. (author), Mellema, J.R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)

1H nuclear magnetic resonance (NMR) spectroscopy of rat urine in combination with pattern recognition analysis was evaluated for early noninvasive detection of toxicity of investigational chemical entities. Bromobenzene (B) and paracetamol (P) were administered at five single oral dosages between 2 and 500 mg/kg and between 6 and 1800 mg/kg,...

article 2007

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Comfort predictors for different kinds of hand tools: Differences and similarities

Kuijt-Evers, L.F.M. (author), Vink, P. (author), de Looze, M.P. (author), TNO Kwaliteit van Leven (author)

This study investigates whether the same factors underlie comfort in using different kinds of hand tools (screwdrivers, paintbrushes and handsaws). The underlying factors of the hand tools are identified using principal components analysis. The relationships between comfort descriptors (i.e. statements in end-users' own words that are related to...

article 2007

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Discovering gene expression patterns in time course microarray experiments by ANOVA-SCA

Nueda, M.J. (author), Conesa, A. (author), Westerhuis, J.A. (author), Hoefsloot, H.C.J. (author), Smilde, A.K. (author), Talón, M. (author), Ferrer, A. (author), TNO Kwaliteit van Leven (author)

Motivation: Designed microarray experiments are used to investigate the effects that controlled experimental factors have on gene expression and learn about the transcriptional responses associated with external variables. In these datasets, signals of interest coexist with varying sources of unwanted noise in a framework of (co)relation among...

article 2007

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Uniform procedure of 1H NMR analysis of rat urine and toxicometabonomics Part II: Comparison of NMR profiles classification of hepatotoxicity

Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.-P.H.T.M. (author), Smit, M.J. (author), Zandberg, P. (author), Horbach, G.J. (author), Mellema, J.-R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)

A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition is proposed for early detection of toxicity of investigational compounds in rats. The method is applied to detect toxicity upon administration of 13 toxic reference compounds and one nontoxic control compound (mianserine) in rats. The toxic compounds are...

article 2007

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Statistical validation of megavariate effects in ASCA

Vis, D.J. (author), Westerhuis, J.A. (author), Smilde, A.K. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

Background: Innovative extensions of (M) ANOVA gain common ground for the analysis of designed metabolomics experiments. ASCA is such a multivariate analysis method; it has successfully estimated effects in megavariate metabolomics data from biological experiments. However, rigorous statistical validation of megavariate effects is still...

article 2007

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Quantitative self-assessment of exposure to solvents among shoe repair men

TNO Kwaliteit van Leven (author), Hertsenberg, S. (author), Brouwer, D. (author), Lurvink, M. (author), Rubingh, C. (author), Rijnders, E. (author), Tielemans, E. (author)

Self-assessment of exposure (SAE) refers to any exposure assessment methodology wherein the worker takes an active role in establishing his or her exposure status. The objective of this study was to investigate the reliability and feasibility of SAE approaches among shoe repair workers collecting exposure data over a 3 month period. This study...

article 2007

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Comparison of coumarin-induced toxicity between sandwich-cultured primary rat hepatocytes and rats in vivo: A toxicogenomics approach

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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Multivariate analysis of microarray data by principal component discriminant analysis: Prioritizing relevant transcripts linked to the degradation of different carbohydrates in Pseudomonas putida S12

van der Werf, M.J. (author), Pieterse, B. (author), van Luijk, N. (author), Schuren, F. (author), van der Werff van der - Vat, B. (author), Overkamp, K. (author), Jellema, R.H. (author), TNO Kwaliteit van Leven (author)

The value of the multivariate data analysis tools principal component analysis (PCA) and principal component discriminant analysis (PCDA) for prioritizing leads generated by microarrays was evaluated. To this end, Pseudomonas putida S12 was grown in independent triplicate fermentations on four different carbon sources, i.e. fructose, glucose,...

article 2006

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Integration of two-dimensional LC-MS with multivariate statistics for comparative analysis of proteomic samples

Gaspari, M. (author), Verhoeckx, K.C.M. (author), Verheij, E.R. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

LC-MS-based proteomics requires methods with high peak capacity and a high degree of automation, integrated with data-handling tools able to cope with the massive data produced and able to quantitatively compare them. This paper describes an off-line two-dimensional (2D) LC-MS method and its integration with software tools for data preprocessing...

article 2006

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Simulations under uncertainty for occupant safety for a vehicle subjected to a blast load

Sun, J. (author), Vlahopoulos, N. (author), Stabryla, T.J. (author), Goetz, R. (author), van de Velde, R. (author), TNO Industrie en Techniek (author)

One of the main threats to military vehicles originates from landmine blasts. In order to improve the survivability of the occupants it is important to design a military vehicle for increased occupant safety. Simulation technology that combines modeling of the blast loads from the landmine explosion, the response of the vehicle to the blast load...

conference paper 2006

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Study of metabolite composition of eccrine sweat from healthy male and female human subjects by 1H NMR spectroscopy

Harker, M. (author), Coulson, H. (author), Fairweather, I. (author), Taylor, D. (author), Daykin, C.A. (author), TNO Voeding (author)

The aim of the study was to evaluate metabolite variability in human eccrine sweat using a metabonomics based approach. Eccrine sweat is a dilute electrolyte solution whose primary function is to control body temperature via evaporative cooling. Although the composition of sweat is primarily water, previous studies have shown that a diverse...

article 2006

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Blast event simulation for a structure subjected to a landmine explosion

Sun, J. (author), Vlahopoulos, N. (author), Stabryla, T.J. (author), Goetz, R. (author), van de Velde, R. (author), TNO Industrie en Techniek (author)

One of the main threats to military vehicles originates from landmine blasts. In order to improve the survivability of the occupants it is important to design a military vehicle for increased occupant safety. Simulation technology that combines modeling of the blast loads from the landmine explosion, the response of the vehicle to the blast load...

conference paper 2006

document

Effects of growth conditions and processing on Rehmannia glutinosa using fingerprint strategy

Chang, W.T. (author), Thissen, U. (author), Ehlert, K.A. (author), Koek, M.M. (author), Jellema, R.H. (author), Hankemeier, T. (author), van der Greef, J. (author), Wang, M. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Metabolite profiling in combination with multivariate statistics is a sophisticated method for quality assessment of natural products. For the development of a quality control strategy in Traditional Chinese Medicine (TCM), we have measured the metabolite fingerprints of Rehmannia glutinosa by GC-MS. Plants were grown under different climate and...

article 2006

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The effectiveness of high-intensity versus low-intensity back schools in an occupational setting: A pragmatic randomized controlled trial

Heymans, M.W. (author), de Vet, H.C.W. (author), Bongers, P.M. (author), Knol, D.L. (author), Koes, B.W. (author), van Mechelen, W. (author), TNO Kwaliteit van Leven (author)

Study Design. Randomized controlled trial. Objectives. To compare high- and low-intensity back schools with usual care in occupational health care. Summary of Background Data. The content and intensity of back schools vary widely and the methodologic quality of randomized controlled trials is generally weak. Until now, no back school has proven...

article 2006

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Centering, scaling, and transformations: Improving the biological information content of metabolomics data

TNO Kwaliteit van Leven (author), van den Berg, R.A. (author), Hoefsloot, H.C.J. (author), Westerhuis, J.A. (author), Smilde, A.K. (author), van der Werf, M.J. (author)

Background: Extracting relevant biological information from large data sets is a major challenge in functional genomics research. Different aspects of the data hamper their biological interpretation. For instance, 5000-fold differences in concentration for different metabolites are present in a metabolomics data set, while these differences are...

article 2006

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Response of apolipoprotein E*3-Leiden transgenic mice to dietary fatty acids: Combining liver proteomics with physiological data

de Roos, B. (author), Duivenvoorden, I. (author), Rucklidge, G. (author), Reid, M. (author), Ross, K. (author), Lamers, R.J.A.N. (author), Voshol, P.J. (author), Havekes, L.M. (author), Teusink, B. (author), TNO Kwaliteit van Leven (author)

article 2005

document

Dietary patterns and breast cancer risk: Results from three cohort studies in the DIETSCAN project

Männistö, S. (author), Dixon, L.B. (author), Balder, H.F. (author), Virtanen, M.J. (author), Krogh, V. (author), Khani, B.R. (author), Berrino, F. (author), van den Brandt, P.A. (author), Hartman, A.M. (author), Pietinen, P. (author), Tan, F. (author), Wolk, A. (author), Goldbohm, R.A. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Objective: Only a few consistent findings on individual foods or nutrients that influence breast cancer risk have emerged thus far. Since people do not consume individual foods but certain combinations of them, the analysis of dietary patterns may offer an additional aspect for assessing associations between diet and diseases such as breast...

article 2005

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Multilevel component analysis of time-resolved metabolic fingerprinting data

Jansen, J.J. (author), Hoefsloot, H.C.J. (author), van der Greef, J. (author), Timmerman, M.E. (author), Smilde, A.K. (author), TNO Kwaliteit van Leven (author)

Genomics-based technologies in systems biology have gained a lot of popularity in recent years. These technologies generate large amounts of data. To obtain information from this data, multivariate data analysis methods are required. Many of the datasets generated in genomics are multilevel datasets, in which the variation occurs on different...

article 2005

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In search of secreted protein biomarkers for the anti-inflammatory effect of β2-adrenergic receptor agonists: Application of DIGE technology in combination with multivariate and univariate data analysis tools

Verhoeckx, K.C.M. (author), Gaspari, M. (author), Bijlsma, S. (author), van der Greef, J. (author), Witkamp, R.F. (author), Doornbos, R.P. (author), Rodenburg, R.J.T. (author), TNO Kwaliteit van Leven (author)

Two-dimensional difference gel electrophoresis (DIGE) in combination with univariate (Student's t-test) and multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to study the anti-inflammatory effects of the β2-adrenergic receptor (β2-AR) agonist zilpaterol. U937...

article 2005