Cornelis Kluft - Academia.edu (original) (raw)

Papers by Cornelis Kluft

American Heart Journal, 1991

Metabolites

Variation in metabolite levels reflects individual differences in genetic and environmental facto... more Variation in metabolite levels reflects individual differences in genetic and environmental factors. Here, we investigated the role of these factors in urinary metabolomics data in children. We examined the effects of sex and age on 86 metabolites, as measured on three metabolomics platforms that target amines, organic acids, and steroid hormones. Next, we estimated their heritability in a twin cohort of 1300 twins (age range: 5.7–12.9 years). We observed associations between age and 50 metabolites and between sex and 21 metabolites. The monozygotic (MZ) and dizygotic (DZ) correlations for the urinary metabolites indicated a role for non-additive genetic factors for 50 amines, 13 organic acids, and 6 steroids. The average broad-sense heritability for these amines, organic acids, and steroids was 0.49 (range: 0.25–0.64), 0.50 (range: 0.33–0.62), and 0.64 (range: 0.43–0.81), respectively. For 6 amines, 7 organic acids, and 4 steroids the twin correlations indicated a role for shared e...

Translational psychiatry, Jan 21, 2012

Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but ... more Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but the exact nature of this association is still unknown and may be restricted to specific subgroups. This study examines the association between depressive disorders, depression characteristics and antidepressant medication with inflammation in a large cohort of controls and depressed persons, taking possible sex differences and important confounding factors into account. Persons (18-65 years) with a current (N = 1132) or remitted (N = 789) depressive disorder according to DSM-IV criteria and healthy controls (N = 494) were selected from the Netherlands Study of Depression and Anxiety. Assessments included clinical characteristics (severity, duration and age of onset), use of antidepressant medication and inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)). After adjustment for sociodemographics, currently depressed men, but not women,...

Journal of the American College of Cardiology, 1990

Cellular Oncology, 2005

A consensus development meeting was held to evaluate whether or not in the Netherlands all requir... more A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2-3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2-3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2-3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2-3 years...

EJIFCC, 2000

Background Proficiency testing of enzymatic methods for plasminogen activator inhibitor 1 (PAI-1)... more Background Proficiency testing of enzymatic methods for plasminogen activator inhibitor 1 (PAI-1) showed a systematic variability indicating the aspecificity of some methods. Methods To define and detect specificity of enzymatic methods for PAI-1, experts of the ISTH/SSC subcommittee defined criteria and test samples to check the criteria. 16 samples were prepared to test (a) specificity in depleted plasma, (b) interference by added PAI-2 or PAI-3, (c) interference by added tissue-type plasminogen activator (t-PA), (d) performance in dose response. To exercise the test procedure participants were recruited via the subcommittee, literature and company data. Coded samples were distributed to participants. The NIBSC standard for PAI-1 activity was included for the normalisation of results. Adherence to the predetermined criteria was judged blind in the ISTH/SSC subcommittee meeting. Results In total 17 laboratories with 15 different assay methods participated in the study. Methods were...

The Journal of clinical endocrinology and metabolism, 2018

Luteinizing hormone-releasing hormone (LHRH) agonists have replaced estrogens for endocrine treat... more Luteinizing hormone-releasing hormone (LHRH) agonists have replaced estrogens for endocrine treatment of advanced prostate cancer (PC) because of cardiovascular side effects. The fetal estrogen estetrol (E4) may be safer for PC treatment and is expected to decrease testosterone (T) and prevent estrogen deficiency. To investigate the safety and T-suppressive effect of E4 in healthy men. Double-blind, randomized, placebo-controlled, dose-escalating study. The study was conducted at a phase I clinical unit (QPS, Netherlands). Healthy male volunteers aged 40 to 70 years. Three treatment cohorts of 15 volunteers with placebo (n = 5) and E4 (n = 10). Estetrol doses tested were 20, 40, and 60 mg/d. Subjects were treated for 4 weeks. Subjective side effects, pharmacodynamic effects on hemostatic variables, lipids, glucose, bone parameters, and endocrine parameters related to T metabolism. Total and free T decreased dose-dependently and significantly. Nipple tenderness occurred in 40% and de...

Frontiers in cardiovascular medicine, 2018

Treatment with the second and third generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) increas... more Treatment with the second and third generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) increases cardiovascular risk in chronic myeloid leukemia (CML) patients. We investigated the vascular adverse effects of three generations of TKIs in a translational model for atherosclerosis, the APOE*3Leiden.CETP mouse. Mice were treated for sixteen weeks with imatinib (150 mg/kg BID), nilotinib (10 and 30 mg/kg QD) or ponatinib (3 and 10 mg/kg QD), giving similar drug exposures as in CML-patients. Cardiovascular risk factors were analyzed longitudinally, and histopathological analysis of atherosclerosis and transcriptome analysis of the liver was performed. Imatinib and ponatinib decreased plasma cholesterol (imatinib, -69%, < 0.001; ponatinib 3 mg/kg, -37%, < 0.001; ponatinib 10 mg/kg-44%, < 0.001) and atherosclerotic lesion area (imatinib, -78%, < 0.001; ponatinib 3 mg/kg, -52%, = 0.002; ponatinib 10 mg/kg, -48%, = 0.006), which were not affected by nilotinib. In addition, ima...

Clinical chemistry and laboratory medicine, 2018

Antithrombin (AT) is a critical regulator of coagulation, and its overall activity is typically m... more Antithrombin (AT) is a critical regulator of coagulation, and its overall activity is typically measured using functional tests. A large number of molecular forms of AT have been identified and each individual carries multiple molecular proteoforms representing variable activities. Conventional functional tests are completely blind for these proteoforms. A method that ensures properly defined measurands for AT is therefore needed. We here assess whether mass spectrometry technology, in particular multiple reaction monitoring (MRM), is suitable for the quantification of AT and the qualitative detection of its molecular proteoforms. Plasma proteins were denatured, reduced and alkylated prior to enzymatic digestion. MRM transitions were developed towards tryptic peptides and glycopeptides using AT purified from human plasma. For each peptide, three transitions were measured, and stable isotope-labeled peptides were used for quantitation. Completeness of digestion was assessed using dig...

Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, Jan 4, 2018

To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and s... more To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and subretinal fluid (SRF) of rhegmatogenous retinal detachment (RRD) patients and to validate and further specify our earlier finding of increased thrombin activity in patients with proliferative vitreoretinopathy (PVR). F1+2 and TAT were measured in 31 vitreous and 16 SRF samples using the Enzygnost® immunoassays. We found significant levels of F1+2 and TAT in the vitreous of all patients with RRD compared to patients with macular hole or macular pucker. However, there was no significant difference between patients who would develop PVR in the future, had established PVR, and patients with uncomplicated RRD both in vitreous concentrations of F1+2 (Kruskal-Wallis p = 0.963) and TAT (p = 0.516). The analysis of F1+2 and TAT confirmed significant thrombin generation in both vitreous and SRF of patients with RRD. An imbalance between the thrombin regulation mechanisms TAT and α2-macroglobulin p...

Cellular and molecular gastroenterology and hepatology, 2018

The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechan... more The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involv...

Fibrinolysis

... independent epidemiological studies have shown that risk for cardiovascular events is associa... more ... independent epidemiological studies have shown that risk for cardiovascular events is associated with increased molar concentrations of t-PA or PAT-1, or ... sensitivity&quot; and in tPA and PAI1 are correlated in cases with variable insulin sensitivity.&quot;,&#x27; As shown by Potter van Loon et W ...

Journal of Human Genetics

Acta ophthalmologica, Jun 27, 2017

Biomarkers in Medicine, 2016

Aim: Neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) are biomarkers for dis... more Aim: Neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) are biomarkers for disease development, for whom little is known about causes of variation in the general population. Materials & methods: We estimated the heritability of PLR and NLR and examined their association with gender, demographic, lifestyle and environmental factors in a Dutch nonpatient twin family population (n = 8108). Results: Heritability was estimated at 64% for PLR and 36% for NLR. Men had on average higher NLR, but lower PLR levels than women. PLR and NLR increased significantly with age, decreased in colder months and showed small but significant sex- and age-specific associations with body composition and smoking. Conclusion: NLR and PLR levels are heritable and influenced by age, sex and environmental factors, such as seasonal conditions and lifestyle.

Clinical chemistry, Jan 27, 2016

Levels of hemostasis factors vary between and within individuals as a result of genetic and envir... more Levels of hemostasis factors vary between and within individuals as a result of genetic and environmental factors and analytical variation of the assays. The current state of the art for defining analytical precision requirements for analytical testing is based on this between- and within-individual (biological) variation. However, information on biological variation in hemostasis variables is still limited.The aim of this study was to determine the biological variation of coagulation variables involved in thrombosis and bleeding to provide a recommendation for performance specifications and to assess whether hemostasis assays fulfill the recommendation. We performed a longitudinal study by repeated blood sampling (in total 13 times over a 1-year period) in 40 healthy individuals and measured prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, factor VIII, factor IX, von Willebrand factor (VWF), protein C, and protein S. We evaluated the ef...

J Thromb Thrombolysis, 1996