1,100 results on '"RS: NUTRIM - R4 - Gene-environment interaction"'
Search Results
2. Deciphering mitochondrial and molecular pathology in Type 2 Diabetes Mellitus
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van Tienen, F.H.J., Smeets, Bert, de Coo, René, van der Kallen, Carla, Genetica & Celbiologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
3. Cellular and molecular aspects of weight regulation: the adipose tissue
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Bouwman, F.G., Mariman, Edwin, Wang, Ping, Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - HB/BW section A
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obesity ,fat molecules ,yo-yo effect ,diet ,genetic predisposition - Abstract
This dissertation studied the effects of a low-calorie diet on fat molecules and the impact of genes on body weight regulation. We discovered two different genetic variations (the FTO gene in men and the MMP2 gene in women) that predict a weight gain of at least 8 kilos over the course of a decade. Furthermore, it was shown that fat cells increase their ability to include higher levels of glucose and fatty acids following weight loss achieved with a diet. After three weeks, fat cells were found to be craving fat, a mechanism provoking old eating habits (the so-called yo-yo effect). Certain target groups, including people having a genetic predisposition, should therefore receive improved weight-loss and/or weight-maintenance counselling.
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- 2021
4. Exploratory pathway analysis
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Kelder, T.A.J., van Schooten, Frederik, Evelo, Chris, Bioinformatica, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
5. Oxidative stress responses in hepatocarcinogenesis: unravelling the mechanisms using a toxicogenomics approach
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Deferme, L., Kleinjans, Joseph, Briedé, Jacco, GezondheidsRisico Analyse en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
6. Short- and long-term cardiometabolic consequences of infant growth: size matters
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Touwslager, R.N., Zimmermann, Luc, Stehouwer, Coen, Mulder, Antonius, Gielen, Marij, Kindergeneeskunde, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
7. The role of the skeletal muscle in the early onset of the metabolic syndrome : a nutrigenomics approach
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de Wilde, J., Mariman, Edwin, Smit, Egbert, Humane Biologie, and RS: NUTRIM - R4 - Gene-environment interaction
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muscle ,digestive, oral, and skin physiology ,high-fat food ,metabolic syndrome - Abstract
The muscle plays an important role in the development of the metabolic syndrome (metabolic disease due to an imbalance between eating and exercising). The worldwide increase of the metabolic syndrome is caused by high-fat food. This dissertation describes the effect of high-fat food on the muscle by molecular changes at the gene, protein and fat metabolite level. High-fat food causes molecular changes in the muscle that indicate an increase of the capacity of the fat metabolism. By actually measuring the fat metabolism the molecular changes were confirmed. These findings show how molecular research can be successfully integrated with more applied research. (This research was financed by the Nutrigenomics Consortium of TI Food and Nutrition).
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- 2021
8. Proteomic, transcriptomic and epidemiological analysis of adipocyte-secreted proteins'towards a system biological understanding of adipocytes
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Wang, P., Renes, Johan, Keijer, J., Mariman, Edwin, Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
9. Advancement of the Brown Norway rat as a model for food allergy : route of exposure - immunomodulation - allergogenomics
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de Jonge, J.D., van Loveren, Henk, Knippels, L.M., Ezendam, J., Gezondheidsrisico Analyse en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
10. Polycyclic aromatic hydrocarbon induced effects on gene expression in relation to carcinogenic potency
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Staal, Y.C., van Schooten, Frederik, van Delft, Joseph, Gezondheidsrisico Analyse en Toxicologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
11. Toxicogenomics responses in the in vitro liver : a view on human interindividual variation
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Jetten, M.J.A., Kleinjans, Joseph, GezondheidsRisico Analyse en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
12. Pharmacokinetics and pharmacogenetics of tacrolimus in renal transplant patients
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R. Op den Buisch, Visser - van Dieijen, Marja, Bekers, Otto, MUMC+: DA CDL Algemeen (9), RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: NUTRIM - R4 - Gene-environment interaction
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Oncology ,medicine.medical_specialty ,Pharmacokinetics ,business.industry ,Renal transplant ,Internal medicine ,Medicine ,Pharmacology ,business ,Tacrolimus ,Pharmacogenetics - Published
- 2021
13. Detection of developmental toxicity using differentiating embryonic stem cells : a transcriptomic approach
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van Dartel, D.A., Kleinjans, Joseph, Piersma, A.H., Pennings, J.L., GezondheidsRisico Analyse en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
14. Epidemiology of pancreatic cancer : a global approach
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Bosetti, C., Zeegers, Maurice, La Vecchia, Carlo, Complexe Genetica, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
15. Role of neutrophils in pulmonary DNA damage and repair
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Güngör, N., van Schooten, Frederik, Godschalk, Roger, Knaapen, Ad, Gezondheidsrisico Analyse en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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- 2021
16. Protein biomarkers in chronic disease : proteomics-driven discovery
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Pulinx, B., Visser - van Dieijen, Marja, Schurink, Gerardus, Wodzig, Will, MUMC+: DA CDL Algemeen (9), and RS: NUTRIM - R4 - Gene-environment interaction
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Proteomics ,Multiple Sclerosis (MS) ,cardiovascular system ,abdominal aorta aneurysm (AAA) ,Biomarkers ,Donor kidneys - Abstract
For this dissertation proteomics techniques were used to find new/better biomarkers for aneurisms of the abdominal aorta (AAA), Multiple Sclerosis (MS) and the quality of donor kidneys. It is shown that certain proteins in the blood are associated with AAA size and growth, and can be helpful in determining a successful surgical intervention to treat the AAA. Moreover, in the perfusion liquid of donor kidneys proteins were found that are an indication for the vital strength of the transplant and the degree of protein glycation in the cerebrospinal liquid, which can play a role in unravelling the development of MS.
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- 2021
17. Dietary manipulation of fat metabolism in relation to obesity and insulin resistance
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Konings, E., Blaak, Ellen, Mariman, Edwin, Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R1 - Metabolic Syndrome
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- 2021
18. Volatile metabolites in breath strongly correlate with gut microbiome in CD patients
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Paul H. M. Savelkoul, Daisy Jonkers, Danyta I. Tedjo, Lionel Blanchet, John Penders, Marieke Pierik, Ad A.M. Masclee, Jan W. Dallinga, Agnieszka Smolinska, Frederik-Jan van Schooten, Alexander Bodelier, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, RS: NUTRIM - R2 - Gut-liver homeostasis, Promovendi NTM, Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R4 - Gene-environment interaction, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, MUMC+: DA Medische Microbiologie en Infectieziekten (5), and RS: CAPHRI - R4 - Health Inequities and Societal Participation
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0301 basic medicine ,Male ,Microorganism ,Gut flora ,Biochemistry ,Inflammatory bowel disease ,Analytical Chemistry ,0302 clinical medicine ,Crohn Disease ,TUBE MASS-SPECTROMETRY ,METABOLOMIC APPROACH ,Spectroscopy ,FERMENTATION ,biology ,Chemistry ,Gastrointestinal Microbiome ,Middle Aged ,CROHNS-DISEASE ,Crohn's disease ,CHAIN FATTY-ACIDS ,Breath Tests ,Exhalation ,030211 gastroenterology & hepatology ,Female ,PRINCIPAL COMPONENT ANALYSIS ,Adult ,Adolescent ,HUMAN EXHALED AIR ,DIAGNOSIS ,Microbiology ,03 medical and health sciences ,Young Adult ,Canonical correlation analysis ,medicine ,Environmental Chemistry ,Humans ,Microbiome ,Volatile organic compounds ,ORGANIC-COMPOUNDS ,Aged ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Pyrosequencing ,Gas chromatography–mass spectrometry ,Bacteria ,Follow-Up Studies ,INFLAMMATORY-BOWEL-DISEASE - Abstract
Microbiota composition and its metabolic capacity are very important for host health. Evidence suggests that gut microbiome is involved in the metabolites production by host-microbiome interaction. These metabolites can be absorbed in blood and excreted in exhaled air. Although, profiles of gut microbiota and exhaled metabolites were associated with gastrointestinal diseases, a direct link between them has not yet been investigated. The aim of the study was to investigate the relation between volatiles in breath and gut microbiome in active and quiescent Crohn's disease (CD) via a multivariate statistical approach. Canonical correlation analysis (CCA) was used to assess the relation between exhaled metabolites and faecal bacterial species.From 68 CD patients, 184 repeated faecal and breath samples were collected (92 active and 92 quiescent disease). The microbiota composition was assessed by the pyrosequencing of the 16 S rRNA V1-V3 gene region and breath metabolites by gas chromatography mass spectrometry.In active disease, CCA analysis identified 18 metabolites significantly correlated with 19 faecal bacterial taxa (R = 0.91 p-value 3.5*10-4). In quiescent disease 17 volatile metabolites were correlated with 17 bacterial taxa (R = 0.96 p-value 2.8*10-4). Nine metabolites and three bacteria taxa overlapped in active and inactive CD. This is the first study that shows a significant relation between gut microbiome and exhaled metabolites, and was found to differ between active and quiescent CD, indicating various underlying mechanisms. Unravelling this link is essential to increase our understanding on the functional effects of the microbiome and may provide new leads for microbiome-targeted intervention. (C) 2018 Elsevier B.V. All rights reserved.
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- 2018
19. Detection of high-risk carbapenem-resistant Klebsiella pneumoniae and Enterobacter cloacae isolates using volatile molecular profiles
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Christiaan A. Rees, Paola C. Zucchi, Katherine R. Kane, Elizabeth B. Hirsch, Orkan Sezer, Alexa E. Lewis, Yohei Doi, Jane E. Hill, Mavra Nasir, Shannon E. Kossmann, Agnieszka Smolinska, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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0301 basic medicine ,Klebsiella pneumoniae ,lcsh:Medicine ,Drug resistance ,medicine.disease_cause ,EMERGENCE ,Genotype ,polycyclic compounds ,EPIDEMIOLOGY ,lcsh:Science ,Molecular Epidemiology ,OUTCOMES ,Multidisciplinary ,biology ,Enterobacteriaceae Infections ,Enterobacteriaceae ,Anti-Bacterial Agents ,3. Good health ,Europe ,Staphylococcus aureus ,ESCHERICHIA-COLI ,INFECTIONS ,Area Under Curve ,BACTERIA ,Plasmids ,030106 microbiology ,Microbial Sensitivity Tests ,beta-Lactamases ,Article ,Microbiology ,03 medical and health sciences ,Bacterial Proteins ,Drug Resistance, Bacterial ,Enterobacter cloacae ,Escherichia coli ,medicine ,Humans ,STAPHYLOCOCCUS-AUREUS ,Molecular epidemiology ,IDENTIFICATION ,lcsh:R ,MASS-SPECTROMETRY ,biology.organism_classification ,Carbapenem-Resistant Enterobacteriaceae ,030104 developmental biology ,Carbapenems ,ROC Curve ,Genes, Bacterial ,North America ,lcsh:Q ,CLONES - Abstract
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates of K. pneumoniae, Escherichia coli, and Enterobacter cloacae. Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage in K. pneumoniae, ST131 in E. coli, and ST78 and ST171 in E. cloacae. Prior studies have demonstrated that carbapenem-resistant K. pneumoniae differs from carbapenem-susceptible K. pneumoniae at both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates of K. pneumoniae, E. coli, and E. cloacae produce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 for K. pneumoniae and 1.000 for E. cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset of K. pneumoniae isolates further accentuated the metabolic differences observed between ST258 and non-ST258.
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- 2018
20. DNA methylation in childhood asthma
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Mariona Bustamante, Francesco Forastiere, Henriette A. Smit, Petter Mowinckel, Marjan Kerkhof, Tari Haahtela, Martijn C. Nawijn, Raul Aguirre-Gamboa, Dan Mason, Mihai G. Netea, Cisca Wijmenga, Raf Azad, Vegard Hovland, John Wright, Josep M. Antó, Cilla Söderhäll, Pieter van der Vlies, William O.C.M. Cookson, Bianca van Rijkom, Lovisa E. Reinius, Soesma A Jankipersadsing, Leda Chatzi, Nour Baïz, Erik Melén, Daniela Porta, Olena Gruzieva, Juha Kere, Isabella Annesi-Maesano, Maties Torrent, Charles Auffray, Cleo C. van Diemen, Manolis Kogevinas, Davide Gori, Johann Pellet, Jose Ramon Bilbao, Harri Alenius, Göran Pershagen, Sabrina Llop, Miriam F. Moffatt, Nathanaël Lemonnier, Ashok Kumar, Simon Kebede Merid, Nanna Fyhrquist, Stephane Ballereau, Tiina Laatikainen, Cheng-Jian Xu, Johan C. de Jongste, Marc Jan Bonder, Judith Garcia-Aymerich, Karin C. Lødrup Carlsen, J Sunyer, Mikel Basterrechea, Dario Greco, Yang Li, Jean Bousquet, Ulrike Gehring, Catherine Laprise, Maria Pia Fantini, Rosemary R. C. McEachan, Bert Brunekreef, Stefano Guerra, Gerard H. Koppelman, Cornelis J. Vermeulen, Andréanne Morin, Carmen Iñiguez, Kai-Håkon Carlsen, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], University of Helsinki, King‘s College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stockholm County Council, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Keck School of Medicine [Los Angeles], University of Southern California (USC), Azienda Sanitaria Locale [ROMA] (ASL), McGill University and Genome Quebec Innovation Centre, Département des Sciences Fondamentales [Chicoutimi] (DSF), Université du Québec à Chicoutimi (UQAC), European Institute for Systems Biology and Medicine (EISBM), Arizona Respiratory Center, Radboud University Medical Center [Nijmegen], Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Dermatology, Allergology and Venereology, Clinicum, Medicum, Department of Bacteriology and Immunology, HUS Inflammation Center, One Health Chemisch, dIRAS RA-2, Pediatrics, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Matie, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charle, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manoli, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C., Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.
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Male ,0301 basic medicine ,Allergy ,Cytotoxic ,T-Lymphocytes ,[SDV]Life Sciences [q-bio] ,Respiratory System ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,CHILDREN ,Immunoglobulin E ,Epigenesis, Genetic ,Child ,POPULATION ,education.field_of_study ,biology ,Methylation ,3. Good health ,CpG site ,Child, Preschool ,DNA methylation ,Female ,BIOS Consortium ,Life Sciences & Biomedicine ,Pulmonary and Respiratory Medicine ,Population ,PHENOTYPES ,IMMUNITY ,03 medical and health sciences ,Critical Care Medicine ,Genetic ,General & Internal Medicine ,medicine ,Humans ,COHORT ,Epigenetics ,IGE ,EXPOSURE ,Preschool ,education ,Asthma ,Science & Technology ,business.industry ,RHINITIS ,DNA ,DNA Methylation ,medicine.disease ,Eosinophils ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,biology.protein ,GENOMEWIDE ASSOCIATION ,CpG Islands ,business ,COLLECTION ,T-Lymphocytes, Cytotoxic ,Epigenesis ,Genome-Wide Association Study - Abstract
Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p
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- 2018
21. Teacher-evaluated self-regulation is related to school achievement and influenced by parental education in schoolchildren aged 8-12
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Marleen A. J. van Tetering, Renate H. M. de Groot, Jelle Jolles, RS: NUTRIM - R4 - Gene-environment interaction, Psychiatrie & Neuropsychologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, Clinical Child and Family Studies, Faculty of Behavioural and Movement Sciences, LEARN! - Brain, learning and development, LEARN! - Social cognition and learning, Educational Neuroscience, RS-Theme Biopsychology of Learning, Department FEEEL, and RS-Research Line Fostering Effective, Efficient and Enjoyable Learning (FEEEL) (part of WO program)
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BRAIN-DEVELOPMENT ,School achievement ,Parental education ,Early adolescence ,education ,lcsh:BF1-990 ,Psychological intervention ,CHILDREN ,Academic achievement ,DECISION-MAKING ,INDIVIDUAL-DIFFERENCES ,050105 experimental psychology ,Developmental psychology ,MATHEMATICS ,Executive functions ,WORKING-MEMORY ,Psychology ,0501 psychology and cognitive sciences ,SOCIOECONOMIC-STATUS ,General Psychology ,Original Research ,EXECUTIVE FUNCTION ,05 social sciences ,Case-control study ,050301 education ,Late childhood ,lcsh:Psychology ,ADOLESCENCE ,Self-regulation ,IMPULSIVITY ,READING-COMPREHENSION ,0503 education ,SDG 4 - Quality Education - Abstract
There are major inter-individual differences in the school achievements of students aged 8-12. The determinants of these differences are not known. This paper investigates two possible factors: the self-regulation of the student and the educational levels obtained by their parents. The study first investigates whether children with high and low academic achievement differ in their self-regulation. It then evaluates whether there are differences in the self-regulation of children with high and moderate-to-low level of parental education (LPE). The focus was on the self-regulation of students as judged by their teacher. Teacher evaluations were assessed using an observer questionnaire: the Amsterdam Executive Functioning Inventory. Results showed that students with low school achievement had substantially lower teacher-perceived self-regulation than children with high school achievement. Furthermore, teacher-perceived self-regulation was lower for children with moderate-to-low LPE than for children with high LPE. The findings suggest that interventions on the domain of self-regulation skills should be developed and used, particularly in students at risk of poor school achievement.
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- 2018
22. Cord Blood Metabolic Signatures of Birth Weight
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Robinson, Oliver, Keski-Rahkonen, Pekka, Chatzi, Leda, Kogevinas, Manolis, Nawrot, Tim S, Pizzi, Costanza, Plusquin, Michelle, Richiardi, Lorenzo, Robinot, Nivonirina, Sunyer, Jordi, Vermeulen, Roel, Vrijheid, Martine, Vineis, Paolo, Scalbert, Augustin, Chadeau-Hyam, Marc, dIRAS RA-2, One Health Chemisch, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, Medical Research Council (MRC), Commission of the European Communities, dIRAS RA-2, and One Health Chemisch
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Male ,0301 basic medicine ,Indoles ,Physiology ,Biochemistry ,Mass Spectrometry ,Cohort Studies ,Fetal Development ,chemistry.chemical_compound ,0302 clinical medicine ,Pregnancy ,Medicine ,030212 general & internal medicine ,Vitamin A ,Chromatography, High Pressure Liquid ,TRYPTOPHAN-METABOLISM ,RISK ,OUTCOMES ,Chemistry (all) ,Tryptophan ,ASSOCIATION ,Reference Standards ,Fetal Blood ,metabolomics ,Europe ,MOTHER ,Docosahexaenoic acid ,Cord blood ,Metabolome ,Phosphatidylcholines ,cord blood ,GROWTH ,Female ,pathway perturbation ,03 Chemical Sciences ,birth weight ,fetal growth ,metabolism ,Life Sciences & Biomedicine ,Vitamin ,Biochemistry & Molecular Biology ,Mediation (statistics) ,Docosahexaenoic Acids ,Birth weight ,Carnitine shuttle ,Biochemical Research Methods ,Biological pathway ,03 medical and health sciences ,Fetus ,Metabolomics ,Carnitine ,Humans ,BREAST-CANCER ,COHORT ,VITAMIN-A ,Science & Technology ,business.industry ,Infant, Newborn ,Environmental Exposure ,General Chemistry ,PROGESTERONE ,06 Biological Sciences ,AMBIENT AIR-POLLUTION ,030104 developmental biology ,chemistry ,INMA ,Prostaglandins ,FETAL-GROWTH ,Particulate Matter ,business ,EARLY-PREGNANCY - Abstract
Birth weight is an important indicator of maternal and fetal health and a predictor of health in later life. However, the determinants of variance in birth weight are still poorly understood. We aimed to identify the biological pathways, which may be perturbed by environmental exposures, that are important in determining birth weight. We applied untargeted mass-spectrometry-based metabolomics to 481 cord blood samples collected at delivery in four birth cohorts from across Europe: ENVIRONAGE (Belgium), INMA (Spain), Piccolipiu (Italy), and Rhea (Greece). We performed a metabolome-wide association scan for birth weight on over 4000 metabolic features, controlling the false discovery rate at 5%. Annotation of compounds was conducted through reference to authentic standards. We identified 68 metabolites significantly associated with birth weight, including vitamin A, progesterone, docosahexaenoic acid, indolelactic acid, and multiple acylcarnitines and phosphatidylcholines. We observed enrichment (p < 0.05) of the tryptophan metabolism, prostaglandin formation, C21-steroid hormone signaling, carnitine shuttle, and glycerophospholipid metabolism pathways. Vitamin A was associated with both maternal smoking and birth weight, suggesting a mediation pathway. Our findings shed new light on the pathways central to fetal growth and will have implications for antenatal and perinatal care and potentially for health in later life. This work has been supported by the Exposomics EC FP7 grant (grant agreement no: 308610). Data collection in the INMA Sabadell cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176) and the Generalitat de Catalunya (CIRIT 1999SGR 00241). O.R. was supported by an MRC Early Career Fellowship. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Piccolipiii was partially funded by the Italian National Centre for Disease Prevention and Control and by the Italian Ministry of Health.
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- 2018
23. Is early life exposure to polyomaviruses and herpesviruses associated with obesity indices and metabolic traits in childhood?
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Marina Vafeiadi, Angelika Michel, Manolis Kogevinas, Leda Chatzi, Katerina Sarri, Tim Waterboer, Maria Vassilaki, Michael Pawlita, Silvia de Sanjosé, Eftichia Stiakaki, Marianna Karachaliou, Georgia Chalkiadaki, Vasiliki Leventakou, Theano Roumeliotaki, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, and RS: NUTRIM - R4 - Gene-environment interaction
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medicine.medical_specialty ,Waist ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Blood lipids ,030209 endocrinology & metabolism ,HEART-DISEASE ,Antibodies, Viral ,CYTOMEGALOVIRUS-INFECTION ,Body Mass Index ,HUMAN ADENOVIRUS-36 ,03 medical and health sciences ,0302 clinical medicine ,Seroepidemiologic Studies ,Internal medicine ,GREECE ,Epidemiology ,medicine ,Seroprevalence ,Humans ,030212 general & internal medicine ,Obesity ,Child ,MIDDLE-AGED MEN ,Herpesviridae ,RISK ,Polyomavirus Infections ,Nutrition and Dietetics ,Adiponectin ,business.industry ,Leptin ,RHEA BIRTH COHORT ,Herpesviridae Infections ,medicine.disease ,Tumor Virus Infections ,Cross-Sectional Studies ,ATHEROSCLEROSIS ,Child, Preschool ,CRETE ,business ,Polyomavirus ,BURDEN ,Body mass index - Abstract
Background Evidence for an infectious origin of obesity is emerging. We explored whether common viruses were associated with obesity and metabolic traits. Methods We used cross-sectional (n=674) and prospective (n=440) data from children participating at the 4 and 6 years of age follow-up in the Rhea birth cohort. Presence of IgG antibodies to ten polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, HPyV6, HPyV7, TSPyV, MCPyV, HPyV9, and HPyV10) and four herpesviruses (EBV, CMV, HSV-1, and HSV-2) were measured at age 4. Body mass index, waist circumference, and skinfold thickness were measured at age 4 and 6. Data on serum lipids, leptin, and adiponectin were also available. Multivariable linear regression models were used to explore the associations. Results At 4 years of age, seroprevalence to polyomaviruses ranged from 21.0% for HPyV9 to 82.0% for HPyV10. Seroprevalence for EBV, CMV, HSV-1, and HSV-2 was 53.0%, 26.0%, 3.6%, and 1.5% respectively. BKPyV seropositivity was associated with lower BMI SD score at age 4 [-0.21 (95% CI: -0.39, -0.03)] and 6 [-0.27 (95% CI:-0.48, -0.05)], waist circumference at age 4 [-1.12 cm (95% CI: -2.10, -0.15)] and 6 [-1.73 cm (95% CI: -3.33, -0.12)], sum of four skinfolds [-2.97 mm (95% CI: -5.70, -0.24)], and leptin levels at age 4 [ratio of geometric means, 0.83 (95% CI: 0.70, 0.98)]. CMV seropositivity was associated with higher BMI SD score at age 4 [0.28 (95% CI: 0.11, 0.45)] and 6 [0.24 (95% CI: 0.03, 0.45)] and sum of four skinfolds at age 6 [4.75 mm (95% CI: 0.67, 8.83)]. Having "2-3 herpesviruses infections" (versus "0 herpesvirus infections") was associated with higher BMI SD score [0.32, (95% CI: 0.12, 0.53)], waist circumference [1.22 cm (95% CI: 0.13, 2.31)], and sum of four skinfolds [3.26 mm (95% CI: 0.18, 6.35)] at age 4. Polyomaviruses burden was not associated with outcomes. Conclusions A higher herpesviruses burden and CMV seropositivity were associated with obesity traits in childhood.
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- 2018
24. High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age
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Mariza Kampouri, Stathis Papavasiliou, Georgia Chalkiadaki, Manolis Kogevinas, Andriani Kyriklaki, Vasiliki Daraki, Leda Chatzi, Katerina Margetaki, Katerina Koutra, Marina Vafeiadi, Marianna Katrinaki, Theano Roumeliotaki, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, and RS: NUTRIM - R4 - Gene-environment interaction
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Adult ,Male ,BRAIN-DEVELOPMENT ,medicine.medical_specialty ,Pediatrics ,Mothers ,NEUROCOGNITIVE DEVELOPMENT ,030209 endocrinology & metabolism ,Affect (psychology) ,SERUM ,Cohort Studies ,CHEMICALS ,03 medical and health sciences ,D DEFICIENCY ,0302 clinical medicine ,Cognition ,Pregnancy ,Behavior problems ,Developmental and Educational Psychology ,medicine ,Child and adolescent psychiatry ,Animals ,Humans ,Attention deficit hyperactivity disorder ,ADHD ,Prospective Studies ,030212 general & internal medicine ,Vitamin D ,Child ,Prenatal vitamins ,RISK ,OUTCOMES ,Greece ,D-3 ,Confounding ,Preschool children ,Brain ,General Medicine ,Strengths and Difficulties Questionnaire ,medicine.disease ,25-hydroxyvitamin D ,ADULT BRAIN ,Psychiatry and Mental health ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,Psychology - Abstract
Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother–child pairs from the prospective pregnancy cohort, “Rhea” in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity–impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p trend = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p trend = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (
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- 2018
25. WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research
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Chris T. Evelo, Marianthi Kalafati, Jacob Windsor, Martina Kutmon, Pieter Giesbertz, Alexander R. Pico, Lars M. T. Eijssen, Nuno Nunes, Andra Waagmeester, Jonathan Mélius, Egon Willighagen, Kristina Hanspers, Denise Slenter, Friederike Ehrhart, Ryan A. Miller, Anders Riutta, Susan L. Coort, Daniela Digles, Linda Rieswijk, Kozo Nishida, Elisa Cirillo, Marvin Martens, Promovendi NTM, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: FHML MaCSBio, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, RS: NUTRIM - R4 - Gene-environment interaction, Psychiatrie & Neuropsychologie, and RS: MHeNs - R3 - Neuroscience
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Quality Control ,0301 basic medicine ,WikiPathways : Pathways for the people ,Interoperability ,METABOLISM ,Biology ,computer.software_genre ,Bioinformatics ,Bridging (programming) ,World Wide Web ,03 medical and health sciences ,Annotation ,0302 clinical medicine ,Documentation ,Databases, Genetic ,Genetics ,Animals ,Data Mining ,Humans ,Metabolomics ,Database Issue ,Data Curation ,Collective intelligence ,SERVICES ,Search Engine ,Identifier ,030104 developmental biology ,Web service ,ACCESS ,INTEGRATION ,computer ,Databases, Chemical ,Metabolic Networks and Pathways ,Software ,030217 neurology & neurosurgery - Abstract
WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities.
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- 2017
26. Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva
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Scott McCulloch, Emily Oken, Marie-France Hivert, Wei Perng, Leda Chatzi, Christos S. Mantzoros, Sheryl L. Rifas-Shiman, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R3 - Respiratory & Age-related Health
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0301 basic medicine ,Leptin ,Male ,Endocrinology, Diabetes and Metabolism ,Metabolite ,BINDING-PROTEINS ,Mass Spectrometry ,Body Mass Index ,chemistry.chemical_compound ,Endocrinology ,Pregnancy ,Birth Weight ,Insulin ,LOW-BIRTH-WEIGHT ,Insulin-Like Growth Factor I ,INSULIN-RESISTANCE ,Anthropometry ,Fetal Blood ,Branched-chain amino acids ,Birth size ,Cord blood ,Female ,Adiponectin ,medicine.symptom ,CHILDHOOD OBESITY ,medicine.medical_specialty ,Cord blood hormones ,Context (language use) ,Gestational Age ,Biology ,Article ,03 medical and health sciences ,Insulin resistance ,Insulin-Like Growth Factor II ,Internal medicine ,medicine ,Humans ,Metabolomics ,FOOD FREQUENCY QUESTIONNAIRE ,Neonatal adiposity ,Fetus ,INTRAUTERINE GROWTH ,Infant, Newborn ,medicine.disease ,Low birth weight ,030104 developmental biology ,Insulin-Like Growth Factor Binding Protein 3 ,chemistry ,FETAL-GROWTH ,GLUCOSE-TOLERANCE ,EARLY-PREGNANCY ,HUMAN FETUS - Abstract
Context. Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk.Objectives. To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics.Methods. Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components ("factors"). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns.Results. Mean BW/GA z-score was 0.27 +/- 0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.871 ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern.Conclusions. Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3. (C) 2017 Elsevier Inc. All rights reserved.
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- 2017
27. Adverse outcome pathways: opportunities, limitations and open questions
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Alberto Mantovani, Tanja Waldmann, Bob van de Water, Cristina Cadenas, Hennicke Kamp, Thomas Braunbeck, Annemarie H. Meijer, Mathieu Vinken, Sylvia Escher, Domenico Gadaleta, Patricio Godoy, Anna Forsby, Stefan Schildknecht, Chris T. Evelo, Stefan Höhme, Rosemarie Marchan, Gerhard F. Ecker, Harry Vrieling, Susanne Hougaard Bennekou, Ciarán Fisher, Alice Limonciel, Enrico Mombelli, Rabea Graepel, Marcel Leist, Ahmed Ghallab, Michael Schwarz, Joost B. Beltman, Jens M. Kelm, Albert Braeuning, Olivier Taboureau, Bart van der Burg, Andrea Terron, Ferran Sanz, Frédéric Y. Bois, Steven Dooley, Dinant Kroese, Jan G. Hengstler, Paul Jennings, Egon Willighagen, Barbara Zdrazil, Barry Hardy, Erik H.J. Danen, Bjørn E. V. Koch, David A. Fluri, Christoph van Thriel, Dirk Drasdo, Ben van Ravenzwaay, Iain Gardner, Franz Oesch, Reham Hassan, Raymond Reif, Marvin Martens, Thomas Hartung, University of Konstanz, Department of Forensic Medicine and Veterinary Toxicology [Qena], Faculty of Veterinary Medicine [Qena], South Valley University [Qena]-South Valley University [Qena], Universiteit Leiden, Leibniz Research Centre for Working Environment and Human Factors [Dortmund] (IFADO), Technische Universität Dortmund [Dortmund] (TU), The Danish Epidemiology Science Centre, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Vrije Universiteit Brussel (VUB), BASF [Ludwigshafen], SimCYP Ltd, Institut National de l'Environnement Industriel et des Risques (INERIS), Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig, Medical University Graz, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), University of Heidelberg, Medical Faculty, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), InSphero [Schlieren], University of Vienna [Vienna], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BioDetection Systems, Universität Mannheim, Maastricht University [Maastricht], Institut National de la Santé et de la Recherche Médicale (INSERM), IT University of Copenhagen (ITU), Istituto Superiore di Sanità (ISS), Douglas Connect GmbH, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Carl Zeiss SMT AG, Carl Zeiss, Oberkochen, Faculty of Biology, Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University [Austria] (IMU), BASF, DRC/VIVA/METO, Institut National de l'Environnement Industriel et des Risques, Department of Experimental and Clinical Pharmacology andToxicology [Tübingen], Eberhard Karls Universität Tübingen, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Institute for Health and Consumer Protection, European Commission - Joint Research Centre, Université Grenoble Alpes - UFR Médecine [ ?-2019] (UGA UFRM [ ?-2019]), Molecular Hepatology - Alcohol Associated Diseases, Department of Medicine II, University of Heidelberg, Medical Faculty of Mannheim-University of Heidelberg, Medical Faculty of Mannheim, BigCat - Bioinformatics and Systems Biology Research Group, UMR-S973, MTi, Université Paris Diderot - Paris 7 (UPD7), Department of Immunology and Cell Biology, Mario Negri Institute, Leiden University, Vrije Universiteit [Brussels] (VUB), Universiteit Leiden [Leiden], BASF SE, 67056 Ludwigshafen, Johannes Gutenberg - University of Mainz (JGU), Centre for Alternatives to Animal Testing (CAAT EU), Universitat Pompeu Fabra [Barcelona], European Food Safety Authority = Autorité européenne de sécurité des aliments, Université Grenoble Alpes (UGA), Universität Mannheim [Mannheim], Istituto Superiore di Sanita [Rome], Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Johannes Gutenberg - Universität Mainz (JGU), IT University of Copenhagen, Molecular and Computational Toxicology, AIMMS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Promovendi NTM, RS: FHML MaCSBio, Publica, Pharmaceutical and Pharmacological Sciences, Connexin Signalling Research Group, Liver Connexin and Pannexin Research Group, and Experimental in vitro toxicology and dermato-cosmetology
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CCl4 ,0301 basic medicine ,Proof of non-toxicity ,Health, Toxicology and Mutagenesis ,CCl ,RAPID - Risk Analysis for Products in Development ,Biomedical Innovation ,Signal transduction ,Ecotoxicology ,Toxicology ,NATURAL-KILLER-CELLS ,Prioritization of compounds ,Life ,Adverse Outcome Pathway ,ACTIVATED STELLATE CELLS ,ComputingMilieux_MISCELLANEOUS ,Risk assessment ,TUMOR-NECROSIS-FACTOR ,Event (computing) ,EVIDENCE-BASED TOXICOLOGY ,ENVIRONMENTAL CHEMICALS ,General Medicine ,Toxicokinetics ,Multiple hit events Proof of non-toxicity ,Evidence-based toxicology ,Identification (information) ,Paracetamol ,Risk analysis (engineering) ,Vinyl acetate ,RISK-ASSESSMENT ,Systems biology ,Construct (philosophy) ,Healthy Living ,Human ,Quality Control ,READ-ACROSS ,Vinyl Compounds ,Plasticity ,Liver fibrosis ,Nanotechnology ,Harmonization ,Multiple hit events ,Biology ,History, 21st Century ,Risk Assessment ,Binning of events ,Adverse outcome ,03 medical and health sciences ,Adverse outcome pathway ,SDG 3 - Good Health and Well-being ,ddc:570 ,Tumor promotion ,Journal Article ,Animals ,Humans ,Vinyl acetate Tumor promotion ,Regulatory toxicology ,Set (psychology) ,Epidemiological data ,Adverse Outcome Pathways ,Interspecies extrapolation ,030111 toxicology ,SYSTEMS TOXICOLOGY ,Nonhuman ,Toxicity assay ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation ,Mice, Inbred C57BL ,Multi-scale integration ,Metabolism ,030104 developmental biology ,DEVELOPMENTAL NEUROTOXICITY ,Computational toxicology ,ELSS - Earth, Life and Social Sciences ,Pathway unidirectionality - Abstract
Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field. © 2017, Springer-Verlag GmbH Germany.
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- 2017
28. Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
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Jan Damoiseaux, Kathleen Vrolix, Marc H. De Baets, Socrates J. Tzartos, Peter C. M. Molenaar, Alexander Marx, Konstantinos Lazaridis, Barbie M. Machiels, Mario Losen, Richard Webster, Jo Stevens, Angela Vincent, Pilar Martinez-Martinez, Hakan Cetin, Gisela Nogales-Gadea, Inga Koneczny, Abhishek Saxena, Katja Simon-Keller, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Promovendi MHN, Ondersteunend personeel MHN, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, and MUMC+: MA Med Staf Spec CTC (9)
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0301 basic medicine ,lcsh:Medicine ,Protein Engineering ,FETAL ANTIGEN ,law.invention ,0302 clinical medicine ,Pregnancy ,law ,Receptors, Cholinergic ,lcsh:Science ,B-Lymphocytes ,THYMUS ,Multidisciplinary ,biology ,Chemistry ,Antibodies, Monoclonal ,Recombinant Proteins ,3. Good health ,medicine.anatomical_structure ,B-CELLS ,Recombinant DNA ,Female ,Antibody ,medicine.drug_class ,CLASSICAL COMPLEMENT ACTIVATION ,Monoclonal antibody ,Article ,Neuromuscular junction ,03 medical and health sciences ,Fetus ,FAB-ARM EXCHANGE ,Myasthenia Gravis ,medicine ,SOMATIC HYPERMUTATION ,Humans ,Amino Acid Sequence ,NICOTINIC ACETYLCHOLINE-RECEPTOR ,Binding site ,ARTHROGRYPOSIS MULTIPLEX CONGENITA ,Acetylcholine receptor ,NEUROMUSCULAR-JUNCTION ,lcsh:R ,Autoantibody ,medicine.disease ,Molecular biology ,Myasthenia gravis ,030104 developmental biology ,biology.protein ,AUTOANTIBODIES ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
We report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the γ-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines. Mab 131 blocked one of the two α-bungarotoxin binding sites on the fetal AChR, and partially blocked the binding of an antibody (mAb 637) to the α-subunit of the AChR, suggesting that both antibodies bind at or near one ACh binding site at the α/γ subunit interface. However, mAb 131 did not reduce fetal AChR ion channel currents in electrophysiological experiments. These results indicate that mAb 131, although generated from an MG patient, is unlikely to be pathogenic and may make it a potentially useful reagent for studies of myasthenia gravis, rhabdomyosarcoma and arthrogryposis multiplex congenita which can be caused by fetal-specific AChR-blocking autoantibodies.
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- 2017
29. Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood
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Fabienne Pelé, Ulrike Gehring, Carolina Moltó-Puigmartí, Marin Strøm, Tanja G. M. Vrijkotte, Emily Oken, Costanza Pizzi, Manolis Kogevinas, Leda Chatzi, Henrique Barros, Martine Vrijheid, Maurice P. Zeegers, Theano Roumeliotaki, Jordi Sunyer, Sian M. Robinson, John Mehegan, Andreia Oliveira, Lorenzo Richiardi, Maria Pia Fantini, Sylvaine Cordier, Ferran Ballester, Nina Iszatt, Herman T. den Dekker, Greet Schoeters, Monique Mommers, Hazel Inskip, Mikel Basterrechea, Carel Thijs, Renate H. M. de Groot, Alet H. Wijga, Marij Gielen, Maria Jansen, Nikos Stratakis, Merete Eggesbø, Liesbeth Duijts, Sjurdur F. Olsen, Eva Govarts, Francesco Forastiere, Davide Gori, Daniela Porta, Sheryl L. Rifas-Shiman, Cecily Kelleher, Erasmus MC other, Pediatrics, Epidemiology, Department FEEEL, RS-Research Line Fostering Effective, Efficient and Enjoyable Learning (FEEEL) (part of WO program), Instituto de Saúde Pública, Stratakis, Niko, Roumeliotaki, Theano, Oken, Emily, Ballester, Ferran, Barros, Henrique, Basterrechea, Mikel, Cordier, Sylvaine, de Groot, Renate, den Dekker, Herman T, Duijts, Liesbeth, Eggesbø, Merete, Pia Fantini, Maria, Forastiere, Francesco, Gehring, Ulrike, Gielen, Marij, Gori, Davide, Govarts, Eva, Inskip, Hazel M, Iszatt, Nina, Jansen, Maria, Kelleher, Cecily, Mehegan, John, Moltó-Puigmartí, Carolina, Mommers, Monique, Oliveira, Andreia, Olsen, Sjurdur F, Pelé, Fabienne, Pizzi, Costanza, Porta, Daniela, Richiardi, Lorenzo, Rifas-Shiman, Sheryl L, Robinson, Sian M, Schoeters, Greet, Strøm, Marin, Sunyer, Jordi, Thijs, Carel, Vrijheid, Martine, Vrijkotte, Tanja G M, Wijga, Alet H, Kogevinas, Manoli, Zeegers, Maurice P, Chatzi, Leda, LS IRAS EEPI ME (Milieu epidemiologie), dIRAS RA-2, Complexe Genetica, RS: CAPHRI - R5 - Optimising Patient Care, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: NUTRIM - R4 - Gene-environment interaction, Health Services Research, RS: CAPHRI - R2 - Creating Value-Based Health Care, and Epidemiologie
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Male ,Mediterranean diet ,Epidemiology ,CHILDREN ,Cohort Studies ,0302 clinical medicine ,Fish, Fruit and Other Food ,Surveys and Questionnaires ,Seafood consumption ,Prevalence ,030212 general & internal medicine ,seafood ,Child ,Prenatal Nutritional Physiological Phenomena ,2. Zero hunger ,medicine.diagnostic_test ,JAPANESE INFANTS ,General Medicine ,3. Good health ,Europe ,MEDITERRANEAN DIET ,LUNG-FUNCTION ,Child, Preschool ,Regression Analysis ,Female ,Generation R ,pregnancy ,FATTY-ACIDS ,medicine.symptom ,allergic rhiniti ,Cohort study ,Fish consumption ,WHEEZE ,Asthma - Children ,ECZEMA ,03 medical and health sciences ,children ,Environmental health ,Wheeze ,Fatty Acids, Omega-3 ,medicine ,Animals ,Humans ,Respiratory sounds ,Respiratory Sounds ,Asthma ,PRENATAL EXPOSURE ,fish ,Pregnancy ,allergic rhinitis ,Wheezing ,wheezing ,business.industry ,asthma ,MATERNAL FOOD-CONSUMPTION ,Infant, Newborn ,Infant ,medicine.disease ,Rhinitis, Allergic ,United States ,030228 respiratory system ,Allergic rhinitis - Children ,Relative risk ,GENERATION R ,Human medicine ,business - Abstract
Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood. This work was supported by the European Community’s Seventh Framework Program [EU- FP7- HEALTH-2009-single-stage-241604]. Details of funding per cohort are available at IJE online.
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- 2017
30. The vitamin B6 paradox
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Guido R.M.M. Haenen, Antoon Opperhuizen, Aalt Bast, Geja J. Hageman, Eugène H.J.M. Jansen, Misha F. Vrolijk, Farmacologie en Toxicologie, FSE Campus Venlo, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: NUTRIM - R4 - Gene-environment interaction, RS: CARIM - R3.05 - Vascular remodeling in cardiovascular disease, and RS: CARIM - R2.03 - ECM + Wnt signaling
- Subjects
0301 basic medicine ,Vitamin ,medicine.medical_specialty ,Cell Survival ,Pyridines ,Toxicology ,PREMENSTRUAL-SYNDROME ,VITAMERS ,03 medical and health sciences ,chemistry.chemical_compound ,Polyneuropathies ,0302 clinical medicine ,Internal medicine ,Cell Line, Tumor ,medicine ,Humans ,Viability assay ,Supplements ,OXIDATIVE STRESS ,Pyridoxal ,CONSEQUENCES ,PLASMA ,5'-PHOSPHATE ,Neurotoxicity ,NEUROPATHY ,Pyridoxine ,Lipid metabolism ,Alanine Transaminase ,Neurotoxic ,3-HYDROXYKYNURENINE ,General Medicine ,Vitamins ,Tyrosine Decarboxylase ,medicine.disease ,ALZHEIMERS-DISEASE ,030104 developmental biology ,Endocrinology ,chemistry ,Vitamin B6 ,Toxicity ,Dietary Supplements ,Pyridoxamine ,Caco-2 Cells ,Vitamin B 6 Deficiency ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, > 50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown.In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5phosphate for 24 h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24 h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested.Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine.In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
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- 2017
31. A 20-Year Temporal Change Analysis in Incidence, Presenting Phenotype and Mortality, in the Dutch IBDSL Cohort-Can Diagnostic Factors Explain the Increase in IBD Incidence?
- Author
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Dorien H E van Dongen, Mariëlle Romberg-Camps, Steven Jeuring, Anouk Wolters, Tim van den Heuvel, Wim Hameeteman, Ad A.M. Masclee, Maurice P. Zeegers, Marieke Pierik, Liekele E. Oostenbrug, Daisy Jonkers, Interne Geneeskunde, RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R2 - Gut-liver homeostasis, Complexe Genetica, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: NUTRIM - R4 - Gene-environment interaction, and MUMC+: MA Maag Darm Lever (9)
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Population ,Disease ,ENVIRONMENTAL-FACTORS ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Internal medicine ,Epidemiology ,EVIDENCE-BASED CONSENSUS ,medicine ,Prevalence ,MANAGEMENT ,Humans ,EPIDEMIOLOGY ,Registries ,education ,POPULATION ,Netherlands ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Mortality rate ,Incidence ,Gastroenterology ,General Medicine ,Middle Aged ,medicine.disease ,Inflammatory Bowel Diseases ,Ulcerative colitis ,digestive system diseases ,AMBIENT AIR-POLLUTION ,CROHNS-DISEASE ,time trend ,Phenotype ,ULCERATIVE-COLITIS ,TWINS ,030220 oncology & carcinogenesis ,Cohort ,Immunology ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,business ,INFLAMMATORY-BOWEL-DISEASE - Abstract
Background: The aim was to study temporal changes in incidence, disease phenotype at diagnosis, and mortality of adult inflammatory bowel disease [IBD] patients in South Limburg, The Netherlands, diagnosed between 1991 and 2010. In addition, the 2010 IBD prevalence was estimated.Methods: A multi-faceted approach including hospital administrations, the national pathology registry [PALGA], and general practitioners led to the identification of 1162 patients with Crohn's disease [CD], 1663 with ulcerative colitis [UC], and 84 with unclassified IBD [IBD-U]. Temporal changes in incidence, disease phenotype, and mortality were studied using linear, multinomial regression analyses, and standardised mortality rates [SMR], respectively.Results: The annual incidences increased from 17.90/100000 in 1991 to 40.36/100000 in 2010 for IBD, from 5.84/100000 to 17.49/100000 for CD, and from 11.67/100000 to 21.47/100000 for UC p Conclusions: The IBD incidence in South Limburg increased significantly between 1991 and 2010. The shift towards milder disease at diagnosis in parallel with the improved diagnostics and ability to detect low-grade inflammation was suggestive of an important role of diagnostic factors in this increase. Environmental factors probably played a role as well. The mortality was low and, together with the increasing incidence, led to the high prevalence of IBD in South Limburg.
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- 2017
32. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis
- Author
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Joris Vanderlocht, Frans Stals, Mart van der Cruys, Jan Damoiseaux, Liesbeth E. Bakker-Jonges, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
0301 basic medicine ,Autoimmunity ,Autoimmune hepatitis ,0302 clinical medicine ,Primary biliary cirrhosis ,Immunology and Allergy ,Netherlands ,Reagent Strips ,Immunoassay ,Observer Variation ,biology ,Liver Diseases ,IIf ,Reference Standards ,Mitochondria ,Gastritis ,medicine.symptom ,Antibody ,Quality Control ,Autoimmune Gastritis ,Myocytes, Smooth Muscle ,Immunology ,IMMUNOFLUORESCENCE ,DIAGNOSIS ,CLASSIFICATION ,Autoimmune Diseases ,03 medical and health sciences ,HEPATITIS ,Parietal Cells, Gastric ,Predictive Value of Tests ,medicine ,Humans ,Serologic Tests ,Autoantibodies ,Automation, Laboratory ,030203 arthritis & rheumatology ,Hepatitis ,PRIMARY BILIARY-CIRRHOSIS ,business.industry ,Autoantibody ,Reproducibility of Results ,medicine.disease ,030104 developmental biology ,ANTIBODIES ,biology.protein ,Pernicious anemia ,business ,Biomarkers - Abstract
Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested.For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program.In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. (C) 2017 Elsevier B.V. All rights reserved.
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- 2017
33. Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece
- Author
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Alexandra Pompieri, Antonios Bertsias, Dimitrios T. Boumpas, Antonis Fanouriakis, Prodromos Sidiropoulos, Michalis Tzanakakis, Christina Adamichou, Giorgis Spirou, Ioannis Tzanakis, Leda Chatzi, George Bertsias, Irini Gergianaki, Argyro Repa, Eleni Kabouraki, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R3 - Respiratory & Age-related Health
- Subjects
Male ,Rural Population ,Pediatrics ,Urban Population ,Lupus nephritis ,0302 clinical medicine ,Cost of Illness ,Epidemiology ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Registries ,030212 general & internal medicine ,DISEASE-ACTIVITY INDEX ,Community based ,education.field_of_study ,Systemic lupus erythematosus ,Greece ,Incidence ,Incidence (epidemiology) ,Lupus Vasculitis, Central Nervous System ,STAGE RENAL-DISEASE ,Middle Aged ,Lupus Nephritis ,COLLEGE-OF-RHEUMATOLOGY ,PREVALENCE ,Female ,Neuropsychiatric disease ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Population ,CLINICS CLASSIFICATION CRITERIA ,White People ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,Age Distribution ,Rheumatology ,medicine ,Humans ,DAMAGE INDEX ,NEPHRITIS ,education ,030203 arthritis & rheumatology ,business.industry ,NORTHWEST GREECE ,UPDATED VERSION ,European population ,medicine.disease ,business ,BILAG 2004 - Abstract
ObjectivesSeveral population-based studies on systemic lupus erythematosus (SLE) have been reported, yet community-based, individual-case validated, comprehensive reports are missing. We studied the SLE epidemiology and burden on the island of Crete during 1999–2013.MethodsMultisource case-finding included patients ≥15 years old. Cases were ascertained by the ACR 1997, SLICC 2012 criteria and rheumatologist diagnosis, and validated through synthesis of medical charts, administrative and patient-generated data.ResultsOverall age-adjusted/sex-adjusted incidence was 7.4 (95% CI 6.8 to 7.9) per 100 000 persons/year, with stabilising trends in women but increasing in men, and average (±SD) age of diagnosis at 43 (±15) years. Adjusted and crude prevalence (December 2013) was 123.4 (113.9 to 132.9) and 143 (133 to 154)/105 (165/105 in urban vs 123/105 in rural regions, pConclusionsBy the use of a comprehensive methodology, we describe the full spectrum of SLE from the community to tertiary care, with almost half of the cases having mild disease, yet with significant damage accrual. SLE is not rare, affects predominantly middle-aged women and is increasingly recognised in men. Neuropsychiatric disease is an emerging frontier in lupus prevention and care.
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- 2017
34. Blood pressure in young adulthood and residential greenness in the early-life environment of twins
- Author
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Ruth J. F. Loos, Marij Gielen, Robert Vlietinck, Esmée M. Bijnens, Tim S. Nawrot, Catherine Derom, Maurice P. Zeegers, Department of Environmental Sciences, RS-Research Program Learning and Innovation for Resilient Social-Ecological Systems (LIRSS), Promovendi NTM, Genetica & Celbiologie, Complexe Genetica, RS: NUTRIM - R3 - Respiratory & Age-related Health, and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
Male ,Gerontology ,Blood pressure ,Greenness ,Early-life environment ,Health, Toxicology and Mutagenesis ,CHILDHOOD ,010501 environmental sciences ,01 natural sciences ,NOISE ,0302 clinical medicine ,Belgium ,Residence Characteristics ,Interquartile range ,Medicine and Health Sciences ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Young adult ,Prospective cohort study ,PREDICTORS ,lcsh:Public aspects of medicine ,Confounding ,Environmental exposure ,ASSOCIATION ,LONG-TERM EXPOSURE ,Cohort ,lcsh:Industrial medicine. Industrial hygiene ,Female ,Adult ,Adolescent ,Birth weight ,Environment ,Young Adult ,03 medical and health sciences ,lcsh:RC963-969 ,Humans ,COHORT ,0105 earth and related environmental sciences ,HYPERTENSION ,business.industry ,Research ,MORTALITY ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,Environmental Exposure ,AIR-POLLUTION ,BIRTH-WEIGHT ,Socioeconomic Factors ,business ,Demography - Abstract
Background: Previous research shows that, besides risk factors in adult life, the early-life environment can influence blood pressure and hypertension in adults. However, the effects of residential traffic exposure and residential greenness in the early-life on blood pressure in young adulthood are currently unknown. Methods: Ambulatory (24-h) blood pressures of 278 twins (132 pairs) of the East Flanders Prospective Twins Study were obtained at the age of 18 to 25 years. Prenatal and adulthood residential addresses were geocoded and used to assign prenatal and postnatal traffic and greenness indicators. Mixed modelling was performed to investigate blood pressure in association with greenness while adjusting for potential confounding factors. Results: Night-time systolic blood pressure was inversely associated with greenness at the residential address in twins living at the same address their entire life (non-movers, n = 97, 34.9%). An interquartile increase in residential greenness exposure (1000 m radius) was associated with a 3.59 mmHg (95% CI: -6.0 to -1.23; p = 0.005) lower adult night systolic blood pressure. Among twins who were living at a different address than their birth address at time of the measurement (n = 181, 65.1%), night-time blood pressure was inversely associated with residential surrounding greenness at adult age as well as with residential greenness in early-life. However after additional adjustment for residential greenness exposure in adulthood, only residential greenness exposure in early-life was significantly associated with night systolic blood pressure. While no significant effect of adult residential greenness with adult blood pressure was observed, while accounting for the early-life greenness exposure. Conclusions: Lower residential greenness in the early-life environment was independently associated with a higher adult blood pressure. This indicates that residential greenness has persistent effects on blood pressure. This investigation is supported by the EU research council "project ENVIRONAGE" (ERC-2012-StG 310,890) and Flemish Scientific Fund (G073315 N). Since its start, the East Flanders Prospective Twin Study has been partly supported by grants from the Fund of Scientific Research Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium).
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- 2017
35. Multiplex screening of 422 candidate serum biomarkers in bladder cancer patients identifies syndecan-1 and macrophage colony-stimulating factor 1 as prognostic indicators
- Author
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Douglas G. Ward, Maurice P. Zeegers, Nicholas D. James, Naheema S. Gordon, Ben Abbotts, Richard T. Bryan, Kar Keung Cheng, RS: CAPHRI - R5 - Optimising Patient Care, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,CYSTECTOMY ,medicine.medical_treatment ,NECTIN-4 ,VALIDATION ,Cystectomy ,03 medical and health sciences ,Macrophage Colony-Stimulating Factor 1 ,Circulating tumor cell ,LUNG-CANCER ,MARKERS ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Multiplex ,Lung cancer ,Bladder cancer ,biology ,EPCAM ,syndecan-1 ,medicine.disease ,M-CSF ,CIRCULATING TUMOR-CELLS ,030104 developmental biology ,UROTHELIAL CARCINOMA ,Immunology ,biology.protein ,Biomarker (medicine) ,biomarker ,prognosis ,Antibody ,POOR SURVIVAL ,serum - Abstract
Background: Serum protein biomarkers that correlate with urothelial bladder cancer (UBC) stage and outcome could accelerate and improve clinical management, but this requires thoroughly validated high-performance biomarker(s). Unbiased discovery of serum biomarkers by mass spectrometry is challenging due to their low abundance in a complex sample, and candidate-based discovery is slow and expensive due to the number of immunoassays required. We have utilised a novel multiplex platform to assay disease-associated proteins in the sera of bladder cancer patients with the aim of identifying novel staging and prognostic biomarkers.Methods: All sera were collected as part of the Bladder Cancer Prognosis Programme. We randomly selected 10 non-UBC, 10 G1pTa, 10 G3pTa, 30 G3T1 and 30 G3T2+ UBC cases. Serum levels of proteins were determined with Proseek multiplex immunoassays (http://www.olink.com/). Multivariate linear regression analysis was used to identify significant associations between protein levels and bladder cancer stage and grade. Kaplan-Meier analyses and log-rank tests were used to identify associations between protein levels and disease-specific survival.Results: There were no significant differences in age and gender between the groups. 422 proteins were successfully measured in the sera of the 10 non-cancer controls and 80 UBC patients. Linear regression identified 5 proteins significantly associated with UBC. In order of statistical significance (lowest P value first) these were nectin-4, syndecan-1, T-cell immunoglobulin mucin receptor 1, macrophage colony-stimulating factor 1 and matrilysin. Although none of these showed clear discrimination between stages of disease, high levels of syndecan-1 and macrophage colony-stimulating factor 1 were significantly associated with worse UBC-specific survival.Conclusions: We have studied the relationship between UBC and the serum concentrations of over 400 proteins. Those which reach statistical significance include known biomarkers and new candidates that may warrant further investigation. Although bladder cancer does cause many biologically plausible changes in the serum proteome none of the proteins studied appears to be suitable for accurate non-invasive staging of bladder cancer. However, syndecan-1 and/or macrophage colony stimulating factor-1 (CSF-1) might prove useful as prognostic indicators.
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- 2017
36. Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities
- Author
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Leon A. Frenken, S. Boorsma, S. Gaertner, K.M.L. Leunissen, M. Krekels, E. Litjens, J. van der Net, J. Huitema, Chris P. M. Reutelingsperger, Frank Stifft, W. Grave, E.M. van Duijnhoven, F. de Heer, T.Y. Fung, Sjoerd A.M.E.G. Timmermans, N. ter Braak, Jeroen P. Kooman, M. Gelens, Joris J. J. M. Wirtz, Myrurgia A. Abdul-Hamid, Pieter van Paassen, Jan Damoiseaux, M. H. L. Christiaans, Gaico H. Verseput, Joris Vanderlocht, F.M. van der Sande, Interne Geneeskunde, Promovendi CD, RS: CARIM - R1.02 - Vascular aspects thrombosis and haemostasis, MUMC+: DA Pat Pathologie (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, Biochemie, MUMC+: MA Nefrologie (9), and MUMC+: MA Klinische Immunologie (9)
- Subjects
Pathology ,medicine.medical_specialty ,FACTOR-H ,Thrombotic microangiopathy ,030232 urology & nephrology ,complement dysregulation ,Complement factor I ,030204 cardiovascular system & hematology ,Gene mutation ,urologic and male genital diseases ,ACTIVATION ,03 medical and health sciences ,0302 clinical medicine ,Atypical hemolytic uremic syndrome ,medicine ,genetics ,malignant hypertension ,INHIBITOR ECULIZUMAB ,RECURRENCE ,Kidney transplantation ,medicine.diagnostic_test ,CD46 ,business.industry ,atypical hemolytic uremic syndrome ,RENAL-TRANSPLANTATION ,CLINICAL PHENOTYPE ,medicine.disease ,female genital diseases and pregnancy complications ,C3 MUTATION ,thrombotic microangiopathy ,Nephrology ,Factor H ,HEMOLYTIC-UREMIC SYNDROME ,Renal biopsy ,business ,GENE-MUTATIONS ,AHUS - Abstract
Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon. In six Out of nine patients, we found mutations C3 in three, CFI in one, CD46 in one, and/or CFH in two patients either with or without the risk CFH-H3 haplotype in four patients. Elevated levels of the soluble C5b-9 and renal deposits of C3c and C5b-9 along the vasculature and/or glomerular capillary wall, confirmed complement activation in vivo. In contrast to patients without genetic defects, patients with complement defects invariably progressed to end-stage renal disease, and disease recurrence after kidney transplantation seems common. Thus, a subset of patients with hypertension-associated TMA falls within the spectrum of complement-mediated TMA, the prognosis of which is poor. Hence, testing for genetic complement abnormalities is warranted in patients with severe hypertension and TMA on renal biopsy to adopt suitable treatment options and prophylactic measures.
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- 2017
37. A multicentre study to improve clinical interpretation of proteinase-3 and myeloperoxidase anti-neutrophil cytoplasmic antibodies
- Author
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Elena Csernok, Jan Willem Cohen Tervaert, Niels Rasmussen, Pieter Vermeersch, Xavier Bossuyt, Pieter van Paassen, B Hellmich, Bo Baslund, Daniel Engelbert Blockmans, Jan Damoiseaux, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: MHeNs - R3 - Neuroscience, Faculteit FHML Centraal, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
0301 basic medicine ,vasculitis ,CONSENSUS CONFERENCE ,030207 dermatology & venereal diseases ,0302 clinical medicine ,Proteinase 3 ,NOMENCLATURE ,Medicine ,Pharmacology (medical) ,PR3-ANCA ,Immunoassay ,Likelihood Functions ,microscopic polyangiitis ,medicine.diagnostic_test ,biology ,ANCA ,Area under the curve ,IIf ,MPO-ANCA ,myeloperoxidase ,030220 oncology & carcinogenesis ,Myeloperoxidase ,anti-neutrophil cytoplasmic antibodies ,Antibody ,Granulomatosis with polyangiitis ,Microscopic polyangiitis ,Myeloblastin ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Sensitivity and Specificity ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,Rheumatology ,Humans ,Peroxidase ,030203 arthritis & rheumatology ,GRANULOMATOSIS ,granulomatosis with polyangiitis ,Receiver operating characteristic ,business.industry ,medicine.disease ,030104 developmental biology ,VASCULITIDES ,Case-Control Studies ,Immunology ,biology.protein ,proteinase-3 ,business ,Neutrophil cytoplasmic ,Biomarkers - Abstract
Objective. The objective of this multicentre study was to improve the clinical interpretation of PR3- and MPO-ANCAs as an adjunct for the diagnosis of ANCA-associated vasculitis (AAV) by defining thresholds and test result intervals based on predefined specificities and by calculating test result interval-specific likelihood ratios (LRs).Methods. Eight different PR3- and MPO-ANCA immunoassays from seven companies were evaluated using 251 diagnostic samples from AAV patients and 924 diseased controls.Results. Thresholds for antibody levels were determined based on predefined specificities (95, 97.5, 99 and 100%) and used to delimit test result intervals. Test result interval-specific LRs were determined. For all assays, the LR for AAV increased with increasing antibody level. For all but one immunoassay, high antibodies levels (associated with LR>55) were found in a substantial fraction (>65%) of patients. The area under the curve (AUC) of receiver operating characteristics analysis of a diagnostic approach in which positive results were confirmed by IIF or another immunoassay was not substantially higher than the AUC of performing immunoassay only. The highest AUC was found when immunoassay was combined with another immunoassay or with IIF.Conclusion. To diagnose AAV based on PR3- and MPO-ANCA, it is useful to define thresholds for antibody levels and to assign test result interval-specific LRs. Higher antibody levels are associated with a higher likelihood for disease. Such information improves clinical interpretation.
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- 2017
38. A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss
- Author
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Parastoo Fazelzadeh, Edwin C. M. Mariman, Nadia J. T. Roumans, Marleen A. van Baak, Roel G. Vink, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, RS: NUTRIM - HB/BW section A, and RS: NUTRIM - R1 - Metabolic Syndrome
- Subjects
Male ,0301 basic medicine ,Integrins ,Human dietary intervention ,Gene Expression ,Medicine (miscellaneous) ,Adipose tissue ,Microarray ,Weight Gain ,Body Weight Maintenance ,Extracellular matrix ,Voeding, Metabolisme en Genomica ,chemistry.chemical_compound ,0302 clinical medicine ,Weight loss ,Adipocyte ,Adipocytes ,Leukocytes ,MACROPHAGES ,GENE-EXPRESSION ,INSULIN-RESISTANCE ,Nutrition and Dietetics ,healthy overweight/obese participants ,Middle Aged ,Metabolism and Genomics ,adipose tissue ,Extracellular Matrix ,Very low calorie diet ,Metabolisme en Genomica ,DISEASES ,Nutrition, Metabolism and Genomics ,Female ,human dietary intervention ,medicine.symptom ,microarray ,Risk ,medicine.medical_specialty ,YKL-40 ,Diet, Reducing ,Diet therapy ,food.diet ,Healthy overweight/obese participants ,Weight regain after weight loss ,030209 endocrinology & metabolism ,Biology ,weight regain after weight loss ,03 medical and health sciences ,food ,Insulin resistance ,Voeding ,Extracellular matrix and inflammation ,Internal medicine ,Weight Loss ,medicine ,Humans ,Obesity ,Triglycerides ,Nutrition ,Caloric Restriction ,OVERWEIGHT ,Body Weight ,ADULTS ,medicine.disease ,Subcutaneous Fat, Abdominal ,MAINTENANCE ,030104 developmental biology ,Endocrinology ,chemistry ,Insulin Resistance ,Energy Intake ,CATHEPSIN-S ,extracellular matrix and inflammation - Abstract
Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain. Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain. Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%). Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent. Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415.
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- 2017
39. CD4+CD28null T Cells are related to previous cytomegalovirus infection but not to accelerated atherosclerosis in ANCA-associated vasculitis
- Author
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Peter W. de Leeuw, Jan Willem Cohen Tervaert, Jan Damoiseaux, Alfons J.H.M. Houben, Abraham A. Kroon, Marjan C. Slot, Ruud Theunissen, MUMC+: MA Nefrologie (9), MUMC+: MA Alg Interne Geneeskunde (9), RS: CARIM - R3.02 - Hypertension and target organ damage, Interne Geneeskunde, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Faculteit FHML Centraal
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,MICROSCOPIC POLYANGIITIS ,Intima-media thickness ,Cytomegalovirus ,030204 cardiovascular system & hematology ,Observational Research ,Gastroenterology ,Carotid Intima-Media Thickness ,DISEASE ,0302 clinical medicine ,Immunology and Allergy ,biology ,ANCA ,Middle Aged ,Cytomegalovirus Infections ,cardiovascular system ,Female ,Antibody ,Microscopic polyangiitis ,Vasculitis ,ARTERIAL STIFFNESS ,Systemic vasculitis ,Adult ,medicine.medical_specialty ,OXIDIZED LDL ,Immunology ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,SYSTEMIC VASCULITIS ,03 medical and health sciences ,WEGENERS-GRANULOMATOSIS ,RENAL INVOLVEMENT ,GLOMERULONEPHRITIS ,Rheumatology ,CD28 Antigens ,INFLAMMATION ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Anti-neutrophil cytoplasmic antibody ,Aged ,CD4(+)CD28 T cells ,business.industry ,ACUTE CORONARY SYNDROMES ,medicine.disease ,Atherosclerosis ,030104 developmental biology ,Cross-Sectional Studies ,Arterial stiffness ,biology.protein ,CD4+CD28 T cells ,business - Abstract
Previous studies have suggested an increased risk for cardiovascular events in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). We analyzed the presence of atherosclerotic damage in patients with AAV in relation to the presence of CD4(+)CD28(null) T cells and antibodies against cytomegalovirus (CMV) and human Heat-Shock Protein 60 (hHSP60). In this cross-sectional study, patients with inactive AAV were compared with healthy controls (HC). Carotid intima-media thickness (IMT) and aortic pulse-wave velocity (PWV) were measured. In addition, CD4(+)CD28(null) T cells, anti-CMV, and anti-hHSP60 levels were determined. Forty patients with AAV were included. Patients' spouses were recruited as HC (N = 38). CD4(+)CD28(null) T cells are present in patients with AAV in a higher percentage (median 3.1, range 0.01-85) than in HC (0.28, 0-36, P
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- 2017
40. The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis
- Author
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Daisy Jonkers, Marieke Pierik, Jan W. Dallinga, Alexander Bodelier, F.J. van Schooten, Agnieszka Smolinska, Ad A.M. Masclee, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, RS: NUTRIM - R4 - Gene-environment interaction, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Interne Geneeskunde, and RS: NUTRIM - R2 - Gut-liver homeostasis
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Male ,PATHOGENESIS ,RELAPSE ,01 natural sciences ,Inflammatory bowel disease ,Gastroenterology ,Feces ,0302 clinical medicine ,FECAL CALPROTECTIN ,ENDOSCOPIC ACTIVITY ,Outpatients ,Medicine ,Pharmacology (medical) ,Aged, 80 and over ,biology ,Middle Aged ,Colitis ,Ulcerative colitis ,C-REACTIVE PROTEIN ,CROHNS-DISEASE ,Breath Tests ,Biomarker (medicine) ,Female ,030211 gastroenterology & hepatology ,Adult ,medicine.medical_specialty ,DIAGNOSIS ,Sensitivity and Specificity ,Gas Chromatography-Mass Spectrometry ,03 medical and health sciences ,Internal medicine ,Humans ,Aged ,Volatile Organic Compounds ,Hepatology ,business.industry ,ACTIVITY INDEXES ,010401 analytical chemistry ,C-reactive protein ,medicine.disease ,Faecal calprotectin ,0104 chemical sciences ,Cross-Sectional Studies ,MARKER ,Immunology ,biology.protein ,Gas chromatography–mass spectrometry ,business ,Leukocyte L1 Antigen Complex ,Biomarkers ,INFLAMMATORY-BOWEL-DISEASE - Abstract
SummaryBackground To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. Aim To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. Methods UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index
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- 2017
41. Interactions between dietary acrylamide intake and genes for ovarian cancer risk
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Janneke G. F. Hogervorst, Piet A. van den Brandt, Leo J. Schouten, Roger W. L. Godschalk, Frederik-Jan van Schooten, HOGERVORST, Janneke, van den Brandt, Piet A., Godschalk, Roger W. L., VAN SCHOOTEN, Frederik-Jan, Schouten, Leo J., Epidemiologie, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, Farmacologie en Toxicologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
0301 basic medicine ,Oncology ,EPIC COHORT ,0302 clinical medicine ,Diet and cancer ,Surveys and Questionnaires ,HEMOGLOBIN ADDUCTS ,Genotype ,EPIDEMIOLOGY ,Prospective Studies ,Prospective cohort study ,Cancer ,Ovarian Neoplasms ,Acrylamide ,ASSOCIATION ,Middle Aged ,030220 oncology & carcinogenesis ,Cohort ,GLYCIDAMIDE ,Female ,Cohort study ,Adult ,medicine.medical_specialty ,Dietary acrylamide ,Single nucleotide polymorphism ,Ovarian cancer ,Prospective cohort ,QUESTIONNAIRE ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,PROGESTERONE-RECEPTOR ,POLYMORPHISMS ,METAANALYSIS ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,SCALE PROSPECTIVE COHORT ,medicine.disease ,Diet ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
Some epidemiological studies observed a positive association between dietary acrylamide intake and ovarian cancer risk but the causality needs to be substantiated. By analyzing gene-acrylamide interactions for ovarian cancer risk for the first time, we aimed to contribute to this. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline in 1986, a random subcohort of 2589 women was sampled from the total cohort for a case cohort analysis approach. Dietary acrylamide intake of subcohort members and ovarian cancer cases (n = 252, based on 20.3 years of follow-up) was assessed with a food frequency questionnaire. We selected single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism and in genes involved in the possible mechanisms of acrylamide-induced carcinogenesis (effects on sex steroid systems, oxidative stress and DNA damage). Genotyping was done on DNA from toenails through Agena's Mass-ARRAY iPLEX platform. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions between acrylamide and gene variants after adjustment for multiple testing. However, there were several nominally statistically significant interactions between acrylamide intake and SNPs in the HSD3B1/B2 gene cluster: (rs4659175 (p interaction = 0.04), rs10923823 (p interaction = 0.06) and its proxy rs7546652 (p interaction = 0.05), rs1047303 (p interaction = 0.005), and rs6428830 (p interaction = 0.05). Although in need of confirmation, results of this study suggest that acrylamide may cause ovarian cancer through effects on sex hormones. This study was funded by the Dutch Cancer Society (KWF), grant number: UM 2011-5123. Janneke Hogervorst is a postdoctoral research fellow from the Research Foundation-Flanders (FWO), No. 12J9516N. The authors thank the study participants, the Netherlands Cancer Registry, the Dutch Pathology Registry, and the Biobank of the Maastricht University Medical Center. We thank Dr. Sandra Bausch as initiator of the NLCS study, together with Prof. Piet van den Brandt. We also thank Sacha van de Crommert, Jolanda Nelissen, Conny de Zwart, Ellen Dutman, Henny Brants, and Annemie Pisters for their assistance with data entry or data management, Harry van Montfort for programming assistance, and Stijn Lumeij, Kristien Lemmens, Joy Goessens, and Leonie Jonkers for technical assistance with DNA isolation and genotyping.
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- 2017
42. Detection of antineutrophil cytoplasmic antibodies (ANCAs)
- Author
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Pieter van Paassen, Elena Csernok, Daniel Engelbert Blockmans, Frank Moosig, Pieter Vermeersch, Bo Baslund, Xavier Bossuyt, Jan Damoiseaux, Niels Rasmussen, Jan Willem Cohen Tervaert, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: MHeNs - R3 - Neuroscience, and Faculteit FHML Centraal
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Myeloblastin ,Immunology ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,SYSTEMIC VASCULITIS ,CAPTURE ELISA ,General Biochemistry, Genetics and Molecular Biology ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,0302 clinical medicine ,WEGENERS-GRANULOMATOSIS ,Rheumatology ,Proteinase 3 ,medicine ,Immunology and Allergy ,Fluorescent Antibody Technique, Indirect ,PROTEINASE-3 ,Anti-neutrophil cytoplasmic antibody ,Peroxidase ,030203 arthritis & rheumatology ,Immunoassay ,LINKED-IMMUNOSORBENT-ASSAY ,medicine.diagnostic_test ,business.industry ,Area under the curve ,IIf ,medicine.disease ,MPO-ANCA ,030104 developmental biology ,ROC Curve ,Area Under Curve ,Case-Control Studies ,AUTOANTIBODIES ,business ,Microscopic polyangiitis ,Granulomatosis with polyangiitis ,FOLLOW-UP ,CRESCENTIC GLOMERULONEPHRITIS ,Systemic vasculitis ,INFLAMMATORY-BOWEL-DISEASE - Abstract
ObjectiveThis multicentre study was performed to evaluate the diagnostic accuracy of a wide spectrum of novel technologies nowadays available for detection of myeloperoxidase (MPO) and proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (ANCAs).MethodsSera (obtained at the time of diagnosis) from 251 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 924 disease controls were tested for the presence of cytoplasmic pattern/perinuclear pattern and atypical ANCA (A-ANCA) by indirect immunofluorescence (IIF) (at two sites) and for the presence of PR3-ANCA and MPO-ANCA by eight different immunoassays.ResultsThe area under the curve (AUC) of the receiver operating characteristic curve to discriminate AAV from controls was 0.923 (95% CI 0.902 to 0.944) and 0.843 (95% CI 0.814 to 0.871) for the two IIF methods. For the antigen-specific immunoassays, the AUC varied between 0.936 (95% CI 0.912 to 0.960) and 0.959 (95% CI 0.941 to 0.976), except for one immunoassay for which the AUC was 0.919 (95% CI 0.892 to 0.945).ConclusionsOur comparison of various ANCA detection methods showed (i) large variability between the two IIF methods tested and (ii) a high diagnostic performance of PR3-ANCA and MPO-ANCA by immunoassay to discriminate AAV from disease controls. Consequently, dual IIF/antigen-specific immunoassay testing of each sample is not necessary for maximal diagnostic accuracy. These results indicate that the current international consensus on ANCA testing for AAV needs revision.
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- 2017
43. Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study
- Author
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Frans E. S. Tan, Ronald M.A. Henry, Simone J. S. Sep, Jeroen P. Kooman, Remy J.H. Martens, Frank M. van der Sande, Otto Bekers, Marja P. van Dieijen-Visser, Pieter C. Dagnelie, Karel M.L. Leunissen, Coen D.A. Stehouwer, Carla J.H. van der Kallen, Jeroen D.E. van Suijlen, Dorien M Kimenai, Nicolaas C. Schaper, Miranda T. Schram, Abraham A. Kroon, Steven J.R. Meex, Interne Geneeskunde, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), Promovendi NTM, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, MUMC+: DA CDL Algemeen (9), MUMC+: MA Nefrologie (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, FHML Methodologie & Statistiek, RS: CAPHRI - R1 - Ageing and Long-Term Care, MUMC+: DA CDL (5), RS: NUTRIM - R4 - Gene-environment interaction, RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, MUMC+: MA Alg Interne Geneeskunde (9), RS: CARIM - R3.02 - Hypertension and target organ damage, MUMC+: MA Endocrinologie (9), RS: CAPHRI - R2 - Creating Value-Based Health Care, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and RS: CARIM - R2.02 - Cardiomyopathy
- Subjects
Male ,CHRONIC KIDNEY-DISEASE ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Gastroenterology ,Diabetic nephropathy ,Cohort Studies ,0302 clinical medicine ,TROPONIN-T ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Subclinical infection ,education.field_of_study ,biology ,CYSTATIN C ,STAGE RENAL-DISEASE ,Middle Aged ,CARDIOVASCULAR-DISEASE ,Female ,medicine.symptom ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,ACUTE MYOCARDIAL-INFARCTION ,NT-PROBNP ,Population ,Renal function ,Article ,DIABETIC-NEPHROPATHY ,03 medical and health sciences ,Internal medicine ,medicine ,Albuminuria ,Humans ,Renal Insufficiency, Chronic ,education ,Aged ,business.industry ,NATRIURETIC PEPTIDE ,Biochemistry (medical) ,medicine.disease ,Endocrinology ,Cross-Sectional Studies ,Cystatin C ,Diabetes Mellitus, Type 2 ,Heart Injuries ,biology.protein ,NONDIALYSIS PATIENTS ,business ,Biomarkers ,Kidney disease - Abstract
BACKGROUNDChronic kidney disease (CKD) is associated with an increased cardiovascular disease mortality risk. It is, however, less clear at what point in the course from normal kidney function to CKD the association with cardiovascular disease appears. Studying the associations of estimated glomerular filtration rate (eGFR) and albuminuria with biomarkers of (subclinical) cardiac injury in a population without substantial CKD may clarify this issue.METHODSWe examined the cross-sectional associations of eGFR and urinary albumin excretion (UAE) with high-sensitivity cardiac troponin (hs-cTn) T, hs-cTnI, and N-terminal probrain natriuretic-peptide (NT-proBNP) in 3103 individuals from a population-based diabetes-enriched cohort study.RESULTSAfter adjustment for potential confounders, eGFR and UAE were associated with these biomarkers of cardiac injury, even at levels that do not fulfill the CKD criteria. For example, eGFR 60–CONCLUSIONSeGFR and albuminuria were already associated with biomarkers of (subclinical) cardiac injury at levels that do not fulfill the CKD criteria. Although reduced renal elimination may partly underlie the associations of eGFR, these findings support the concept that eGFR and albuminuria are, over their entire range, associated with cardiac injury.
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- 2017
44. Seasonal Influence on the Risk of Relapse at a Rise of Antineutrophil Cytoplasmic Antibodies in Vasculitis Patients with Renal Involvement
- Author
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Kelly Broen, Pieter van Paassen, Jan Damoiseaux, Jan Willem Cohen Tervaert, Sjoerd A.M.E.G. Timmermans, Michael J. Kemna, Promovendi CD, Faculteit FHML Centraal, Interne Geneeskunde, RS: CARIM - R1.02 - Vascular aspects thrombosis and haemostasis, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL Algemeen (9), and RS: NUTRIM - R4 - Gene-environment interaction
- Subjects
Male ,ANCA-ASSOCIATED VASCULITIS ,PREDICTOR ,030232 urology & nephrology ,ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES ,SEASON ,Kidney ,DISEASE-ACTIVITY ,Gastroenterology ,0302 clinical medicine ,Recurrence ,Risk Factors ,immune system diseases ,Immunology and Allergy ,VITAMIN-D ,FOLLOWUP STUDY ,Middle Aged ,POLYANGIITIS WEGENERS ,Female ,Rituximab ,Seasons ,Vasculitis ,Granulomatosis with polyangiitis ,medicine.drug ,Adult ,medicine.medical_specialty ,Subsequent Relapse ,Cyclophosphamide ,Immunology ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,CLASSIFICATION ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,WEGENERS-GRANULOMATOSIS ,GLOMERULONEPHRITIS ,Rheumatology ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,cardiovascular diseases ,Aged ,Anti-neutrophil cytoplasmic antibody ,030203 arthritis & rheumatology ,business.industry ,Autoantibody ,medicine.disease ,PREVENTION ,VITAMIN D ,GRANULOMATOSIS WITH POLYANGIITIS ,AUTOANTIBODIES ,business - Abstract
Objective.The objective of this study was to identify risk factors for a relapse at the time of an increase in antineutrophil cytoplasmic antibodies (ANCA) in patients with renal ANCA-associated vasculitis (AAV).Methods.All patients between January 2000 and November 2011 with renal AAV having an ANCA rise during remission were included. Differences in time to relapse since the ANCA rise were assessed using a Cox regression model. The level of 25-hydroxy Vitamin D (25(OH)D) was assessed at the ANCA rise and at a subsequent relapse or time-matched during remission.Results.Sixty patients had an ANCA rise, of whom 36 patients relapsed. Three risk factors were associated with a relapse at the time of the ANCA increase: previous disease activity not treated with cyclophosphamide or rituximab (HR 3.48, 95% CI 1.60–7.59), an ANCA rise during the fall season (HR 4.37, 95% CI 1.60–11.90), and an extended ANCA rise (HR 3.57, 95% CI 1.50–8.48). Levels of 25(OH)D significantly decreased during followup in relapsing patients, but not in patients who remained in remission (difference −6.3 ± 14.4, p = 0.017 vs 2.7 ± 16.3, p = 0.430).Conclusion.ANCA rises occurring during the fall season are more frequently followed by a relapse than ANCA rises occurring during other seasons. Although it is tempting to speculate that decreasing Vitamin D levels following the ANCA rise can be held responsible for the subsequent relapse, this remains to be determined.
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- 2017
45. Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans
- Author
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Ellen E. Blaak, Nadia J. T. Roumans, Roel G. Vink, Gijs H. Goossens, Jack P.M. Cleutjens, M. A. A. Vogel, M. A. van Baak, Mark V. Boekschoten, Merima Cajlakovic, Edwin C. M. Mariman, Parastoo Fazelzadeh, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Pathologie, RS: CARIM - R3.06 - The vulnerable plaque: makers and markers, RS: NUTRIM - HB/BW section A, Promovendi NTM, and RS: NUTRIM - R1 - Metabolic Syndrome
- Subjects
Male ,0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Adipose tissue ,HYPOXIA ,Body fat percentage ,Voeding, Metabolisme en Genomica ,chemistry.chemical_compound ,0302 clinical medicine ,HUMAN OBESITY ,Weight loss ,Adipocyte ,CALORIE RESTRICTION ,Adipocytes ,Insulin ,GENE-EXPRESSION ,METABOLIC HEALTH ,Nutrition and Dietetics ,MITOCHONDRIAL BIOGENESIS ,Middle Aged ,Metabolism and Genomics ,Cell Hypoxia ,Oxygen tension ,Phenotype ,Treatment Outcome ,Metabolisme en Genomica ,Nutrition, Metabolism and Genomics ,Female ,medicine.symptom ,medicine.medical_specialty ,Diet, Reducing ,Calorie restriction ,030209 endocrinology & metabolism ,03 medical and health sciences ,Oxygen Consumption ,Voeding ,INFLAMMATION ,Internal medicine ,Weight Loss ,medicine ,Life Science ,Humans ,BETA-ADRENERGIC STIMULATION ,Obesity ,Nutrition ,VLAG ,BLOOD-FLOW ,business.industry ,Overweight ,Subcutaneous Fat, Abdominal ,DYSFUNCTION ,Oxygen ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,chemistry ,Mitochondrial biogenesis ,Insulin Resistance ,business ,Weight gain - Abstract
BACKGROUND/OBJECTIVES: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO(2)), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers and insulin sensitivity in humans.SUBJECTS/METHODS: Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week verylow-calorie diet (VLCD, 500 kcal day(-1); WL), and a subsequent 4-week weight stable diet (WS). Body composition, AT pO(2) (optochemical monitoring), ATBF (Xe-133 washout), and whole-body insulin sensitivity were determined, and AT biopsies were collected at baseline, end of WL (week 5) and end of WS (week 9).RESULTS: Body weight, body fat percentage and adipocyte size decreased significantly during the DI period. The DI markedly decreased AT pO2 and improved insulin sensitivity, but did not alter ATBF. Finally, the DI increased AT gene expression of pathways related to mitochondrial biogenesis and non-mitochondrial oxygen consumption.CONCLUSIONS: VLCD-induced WL markedly decreases abdominal subcutaneous AT pO(2), which is paralleled by a reduction in adipocyte size, increased AT gene expression of mitochondrial biogenesis markers and non-mitochondrial oxygen consumption pathways, and improved whole-body insulin sensitivity in humans.
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- 2017
46. Identification and and Characterization of Cardiac Troponin T Fragments in Serum of Patients Suffering from Acute Myocardial Infarction
- Author
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Douwe de Boer, William P. T. M. van Doorn, Marja P. van Dieijen-Visser, Edwin C. M. Mariman, Alexander S. Streng, Freek G. Bouwman, Will K. W. H. Wodzig, Otto Bekers, MUMC+: DA CDL Algemeen (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Ondersteunend personeel NTM, RS: NUTRIM - HB/BW section A, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: DA CDL (5), and RS: CARIM - R2.02 - Cardiomyopathy
- Subjects
0301 basic medicine ,LABORATORIES ,Clinical Biochemistry ,Myocardial Infarction ,CHROMATOGRAPHY ,030204 cardiovascular system & hematology ,Tandem mass spectrometry ,Proteomics ,03 medical and health sciences ,0302 clinical medicine ,Troponin complex ,Troponin T ,Tandem Mass Spectrometry ,medicine ,Humans ,ASSAYS ,RELEASE ,biology ,Chemistry ,Biochemistry (medical) ,PEPTIDES ,MASS-SPECTROMETRY ,DEGRADATION ,QUANTIFICATION ,Trypsin ,Molecular biology ,TIME ,Blot ,030104 developmental biology ,Targeted mass spectrometry ,Epitope mapping ,Acute Disease ,biology.protein ,PROTEOMICS ,Electrophoresis, Polyacrylamide Gel ,Antibody ,Biomarkers ,medicine.drug - Abstract
BACKGROUNDCardiac troponin T (cTnT) is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). It has been suggested that cTnT is present predominantly in fragmented forms in human serum following AMI. In this study, we have used a targeted mass spectrometry assay and epitope mapping using Western blotting to confirm this hypothesis.METHODScTnT was captured from the serum of 12 patients diagnosed with AMI using an immunoprecipitation technique employing the M11.7 catcher antibody and fractionated with SDS-PAGE. Coomassie-stained bands of 4 patients at 37, 29, and 16 kDa were excised from the gel, digested with trypsin, and analyzed on a Q Exactive instrument set on targeted Selected Ion Monitoring mode with data-dependent tandem mass spectrometry (MS/MS) for identification. Western blotting employing 3 different antibodies was used for epitope mapping.RESULTSTen cTnT peptides of interest were targeted. By using MS/MS, all of these peptides were identified in the 37-kDa, intact, cTnT band. In the 29- and 16-kDa fragment bands, 8 and 4 cTnT-specific peptides were identified, respectively. Some of these peptides were “semitryptic,” meaning that their C-termini were not formed by trypsin cleavage. The C-termini of these semitryptic peptides represent the C-terminal end of the cTnT molecules present in these bands. These results were confirmed independently by epitope mapping.CONCLUSIONSUsing LC-MS, we have succeeded in positively identifying the 29- and 16-kDa fragment bands as cTnT-derived products. The amino acid sequences of the 29- and 16-kDa fragments are Ser79-Trp297 and Ser79-Gln199, respectively.
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- 2017
47. Persistent transcriptional responses show the involvement of feed-forward control in a repeated dose toxicity study
- Author
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Terezinha de Souza, Danyel Jennen, Twan van den Beucken, J.C.S. (Jos) Kleinjans, Linda Rieswijk, Promovendi ODB, Bioinformatica, Promovendi NTM, RS: NUTRIM - R4 - Gene-environment interaction, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: GROW - R1 - Prevention, and Toxicogenomics
- Subjects
0301 basic medicine ,Aflatoxin B1 ,Transcription, Genetic ,Hepatocellular carcinoma ,Regulator ,Gene regulatory network ,Biology ,Toxicology ,medicine.disease_cause ,Transcriptome ,03 medical and health sciences ,medicine ,Humans ,Gene Regulatory Networks ,Transcription factor ,Genetics ,Dose-Response Relationship, Drug ,Hep G2 Cells ,Warburg effect ,Cell biology ,Oxidative Stress ,030104 developmental biology ,HIF1A ,Network motif ,Hepatocytes ,Feed-forward loop ,Oncogene MYC ,Carcinogenesis ,DNA Damage ,Transcription Factors - Abstract
Chemical carcinogenesis, albeit complex, often relies on modulation of transcription through activation or repression of key transcription factors. While analyzing extensive networks may hinder the biological interpretation, one may focus on dynamic network motifs, among which persistent feed-forward loops (FFLs) are known to chronically influence transcriptional programming. Here, to investigate the relevance a FFL-oriented approach in depth, we have focused on aflatoxin B1-induced transcriptomic alterations during distinct states of exposure (daily administration during 5 days followed by a non-exposed period) of human hepatocytes, by exploring known interactions in human transcription. Several TF-coding genes were persistently deregulated after washout of AFB1. Oncogene MYC was identified as the prominent regulator and driver of many FFLs, among which a FFL comprising MYC/HIF1A was the most recurrent. The MYC/HIF1A FFL was also identified and validated in an independent set as the master regulator of metabolic alterations linked to initiation and progression of carcinogenesis, i.e. the Warburg effect, possibly as result of persistent intracellular alterations arising from AFB1 exposure (nuclear and mitochondrial DNA damage, oxidative stress, transcriptional activation by secondary messengers). In summary, our analysis shows the involvement of FFLs as modulators of gene expression suggestive of a carcinogenic potential even after termination of exposure.
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- 2017
48. Weight loss-induced cellular stress in subcutaneous adipose tissue and the risk for weight regain in overweight and obese adults
- Author
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Roel G. Vink, Nadia J. T. Roumans, Parastoo Fazelzadeh, M. A. van Baak, Edwin C. M. Mariman, Freek G. Bouwman, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Ondersteunend personeel NTM, RS: NUTRIM - HB/BW section A, and RS: NUTRIM - R1 - Metabolic Syndrome
- Subjects
0301 basic medicine ,Male ,Galectin 1 ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Overweight ,TARGETED INHIBITION ,Weight Gain ,Body Weight Maintenance ,Voeding, Metabolisme en Genomica ,0302 clinical medicine ,Weight regain ,Weight loss ,Adipocytes ,GENE-EXPRESSION ,INSULIN-RESISTANCE ,Nutrition and Dietetics ,MEN ,Metabolism and Genomics ,DNA-Binding Proteins ,Metabolisme en Genomica ,Female ,Nutrition, Metabolism and Genomics ,medicine.symptom ,INTERVENTIONS ,Adult ,medicine.medical_specialty ,030209 endocrinology & metabolism ,Inflammation ,LOSS MAINTENANCE ,ACTIN ,RATS ,03 medical and health sciences ,Insulin resistance ,INFLAMMATION ,Voeding ,Internal medicine ,Weight Loss ,medicine ,Biomarkers, Tumor ,Life Science ,Humans ,Obesity ,Caloric Restriction ,Nutrition ,Activating Transcription Factor 2 ,business.industry ,Tumor Suppressor Proteins ,Computational Biology ,medicine.disease ,Subcutaneous Fat, Abdominal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Phosphopyruvate Hydratase ,Subcutaneous adipose tissue ,GAIN ,business ,Energy Metabolism - Abstract
BACKGROUND/OBJECTIVE: Weight loss is often followed by weight regain after the dietary intervention (DI). Cellular stress is increased in adipose tissue of obese individuals. However, the relation between cellular stress and weight regain is unclear. Previously, we observed increased adipose tissue cellular stress of participants regaining weight compared with participants maintaining weight loss. In the current study, we further investigated the relation between weight regain and changes in the expression of stress-related genes and stress protein levels to determine possible predictors of weight regain.PARTICIPANTS/METHODS: In this randomized controlled trial, sixty-one healthy overweight/obese participants followed a DI of either a 5-week very-low-calorie diet (500 kcal per day) or a 12-week low-calorie diet (1250 kcal per day; WL period) with a subsequent 4-week weight stable diet (WS period), and a 9-month follow-up. The WL and WS period taken together was named the DI. Abdominal subcutaneous adipose tissue biopsies were collected in 53 participants for microarray and liquid chromatography-mass spectrometry analysis. RNA and protein levels for a broad set of stress-related genes were correlated to the weight regain percentage.RESULTS: Different gene sets correlated to weight regain percentage during WS and DI. Bioinformatics clustering suggests that during the WS phase-defined genes for actin filament dynamics, glucose handling and nutrient sensing are related to weight regain. HIF-1 (hypoxia-inducible factor-1) is indicated as an important regulator. With regard to DI, clustering of correlated genes indicate that LGALS1, ENO1 and ATF2 are important nodes for conferring risk for weight regain.CONCLUSIONS: Our present findings indicate that the risk for weight regain is related to expression changes of distinct sets of stress-related genes during the first 4 weeks after returning to energy balance, and during the DI. Further research is required to investigate the mechanistic significance of these findings and find targets for preventing weight regain.
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- 2017
49. Genetic Predictors of >= 5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects
- Author
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Erik E. J. G. Aller, Freek G. Bouwman, Edwin C. M. Mariman, Marleen A. van Baak, Promovendi NTM, RS: NUTRIM - HB/BW section A, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Ondersteunend personeel NTM, and RS: NUTRIM - R1 - Metabolic Syndrome
- Subjects
Male ,0301 basic medicine ,Lifestyle intervention ,Multifactorial Inheritance ,Candidate gene ,Time Factors ,ACTIVATED RECEPTOR-GAMMA ,LOCI ,Medicine (miscellaneous) ,Gastroenterology ,Nutrigenomics ,0302 clinical medicine ,Weight loss ,Genotype ,Adipocytes ,POPULATION ,METABOLIC SYNDROME ,RISK ,education.field_of_study ,Tissue Inhibitor of Metalloproteinases ,Extracellular matrix ,ASSOCIATION ,Middle Aged ,Obesity, Morbid ,Weight Reduction Programs ,Matrix Metalloproteinase 2 ,Female ,Obese subjects ,medicine.symptom ,Adult ,Fat storage ,Perilipin-1 ,medicine.medical_specialty ,Population ,030209 endocrinology & metabolism ,Polymorphism, Single Nucleotide ,Weight loss maintenance ,03 medical and health sciences ,Internal medicine ,Weight Loss ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,education ,Life Style ,METAANALYSIS ,Original Paper ,Models, Genetic ,business.industry ,Predictors ,medicine.disease ,Adipocyte adaptation ,PPAR gamma ,BODY-MASS INDEX ,030104 developmental biology ,MAINTENANCE ,Metabolic syndrome ,business ,Polymorphisms ,Body mass index ,Food Science - Abstract
Background: Weight loss success is determined by genetic factors, which may differ according to treatment strategy. Methods: From a multidisciplinary obesity treatment program involving dietary advice, psychological counseling, and increased physical activity, 587 subjects (68% female; 46.1 ± 12.4 years; BMI 39.9 ± 6.3) were recruited. At baseline, a blood sample was drawn for DNA isolation. Genotypes were determined for 30 polymorphisms in 25 candidate genes. The association between genotypes and weight loss was assessed after 3 months (short-term) and after 12 months of treatment (long-term). Weight loss was categorized as ≥5% or Results: The G/G genotype of PLIN1 (rs2289487) and PLIN1 (rs2304795), the T/T genotype of PLIN1 (rs1052700), and the C/C genotype of MMP2 predicted ≥5% weight loss in the first 3 months. The C/G-G/G genotype of PPARγ (rs1801282) and the T/C genotype of TIMP4 (rs3755724) predicted ≥5% weight loss after 12 months. Subjects with the combination of PPARγ (rs1801282) C/G-G/G and TIMP4 (rs3755724) T/C lost even more weight. Conclusion: Polymorphisms in genes related to regulation of fat storage and structural adaptation of the adipocytes are predictors for weight loss success with different genes being relevant for short-term and long-term weight loss success.
- Published
- 2017
50. An overview of large-dimensional covariance and precision matrix estimators with applications in chemometrics
- Author
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Lutgarde M. C. Buydens, Jasper Engel, Lionel Blanchet, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R3 - Respiratory & Age-related Health
- Subjects
0301 basic medicine ,GAUSSIAN GRAPHICAL MODELS ,SELECTION ,METABOLOMICS DATA ,Computer science ,Gaussian ,INVERSE ,LASSO ,sparse precision matrix ,01 natural sciences ,TOTAL CORRELATION SPECTROSCOPY ,Analytical Chemistry ,010104 statistics & probability ,03 medical and health sciences ,Matrix (mathematics) ,symbols.namesake ,SPARSE ESTIMATION ,Lasso (statistics) ,Statistics ,SHRINKAGE ESTIMATION ,Graphical model ,PENALIZED NORMAL LIKELIHOOD ,0101 mathematics ,NUCLEAR-MAGNETIC-RESONANCE ,Covariance matrix ,Applied Mathematics ,Estimator ,Covariance ,sparse covariance matrix ,metabolomics ,ridge-type estimation ,030104 developmental biology ,Principal component analysis ,symbols ,eigenvalue shrinkage ,Algorithm - Abstract
The covariance matrix (or its inverse, the precision matrix) is central to many chemometric techniques. Traditional sample estimators perform poorly for high-dimensional data such as metabolomics data. Because of this, many traditional inference techniques break down or produce unreliable results. In this paper, we selectively review several modern estimators of the covariance and precision matrix that improve upon the traditional sample estimator. We focus on 3 general techniques: eigenvalue-shrinkage estimation, ridge-type estimation, and structured estimation. These methods rely on different assumptions regarding the structure of the covariance or precision matrix. Various examples, in particular using metabolomics data, are used to compare these techniques and to demonstrate that in concert with, eg, principal component analysis, multivariate analysis of variance, and Gaussian graphical models, better results are obtained.We selectively review modern estimators of the covariance and precision matrix focusing on 3 general techniques, namely, eigenvalue-shrinkage estimation, ridge-type estimation, and structured estimation. These methods rely on different structural assumptions of the covariance or precision matrix. Various examples, in particular using metabolomics data, are used to compare these techniques and to demonstrate that in concert with, eg, principal component analysis, multivariate analysis of variance, and Gaussian graphical models, better results are obtained.
- Published
- 2017
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