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Rotterdam, Netherlands

Raess P.W.,University of Pennsylvania | van de Geijn G.-J.M.,Sint Franciscus Gasthuis | Njo T.L.,Sint Franciscus Gasthuis | Klop B.,Diabetes and Vascular Center | And 5 more authors.
American Journal of Hematology | Year: 2014

The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index of suspicion to prompt bone marrow studies as well as subjective assessment of dysplastic morphology. We sought to determine if data collected by automated hematology analyzers during complete blood count (CBC) analysis might help to identify MDS in a routine clinical setting. We collected CBC parameters (including those for research use only and cell population data) and demographic information in a large (>5,000), unselected sequential cohort of outpatients. The cohort was divided into independent training and test groups to develop and validate a random forest classifier that identifies MDS. The classifier effectively identified MDS and had a receiver operating characteristic area under the curve (AUC) of 0.942. Platelet distribution width and the standard deviation of red blood cell distribution width were the most discriminating variables within the classifier. Additionally, a similar classifier was validated with an additional, independent set of >200 patients from a second institution with an AUC of 0.93. This retrospective study demonstrates the feasibility of identifying MDS in an unselected outpatient population using data routinely collected during CBC analysis with a classifier that has been validated using two independent data sets from different institutions. © 2013 Wiley Periodicals, Inc. Source

Klop B.,Diabetes and Vascular Center | Van Der Pol P.,Leiden University | Van Bruggen R.,Sanquin Research | Wang Y.,Leiden University | And 13 more authors.
Journal of Biological Chemistry | Year: 2014

Lipoproteins can induce complement activation resulting in opsonization and binding of these complexes to complement receptors. We investigated the binding of opsonized native LDL and acetylated LDL (acLDL) to the complement receptor 1 (CR1). Binding of complement factors C3b, IgM, C1q, mannosebinding lectin (MBL), and properdin to LDL and acLDL were investigated by ELISA. Subsequent binding of opsonized LDL and acLDL to CR1 on CR1-transfected Chinese Hamster Ovarian cells (CHO-CR1) was tested by flow cytometry. Both native LDL and acLDL induced complement activation with subsequent C3b opsonization upon incubation with normal human serum. Opsonized LDL and acLDL bound to CR1. Binding to CHO-CR1 was reduced by EDTA, whereas MgEGTA only reduced the binding of opsonized LDL, but not of acLDL suggesting involvement of the alternative pathway in the binding of acLDL to CR1. In vitro incubations showed thatLDLbound C1q, whereas acLDL bound to C1q, IgM, and properdin. MBL did neither bind to LDL nor to acLDL. The relevance of these findings was demonstrated by the fact that ex vivo up-regulation of CR1 on leukocytes was accompanied by a concomitant increased binding of apolipoprotein B-containing lipoproteins to leukocytes without changes in LDL-receptor expression. In conclusion, CR1 is able to bind opsonized native LDL and acLDL. Binding of LDL to CR1 is mediated via the classical pathway, whereas binding of acLDL is mediated via both the classical and alternative pathways. Binding of lipoproteins to CR1 may be of clinical relevance due to the ubiquitous cellular distribution of CR1. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source

De Vries M.,Diabetes and Vascular Center | Klop B.,Diabetes and Vascular Center | Castro Cabezas M.,Diabetes and Vascular Center
Atherosclerosis | Year: 2014

Current guidelines for the management of dyslipidaemias recommend measuring lipid profiles in the fasting state. The primary lipid targets are traditionally plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. However, triglycerides, apolipoprotein (apo) B and non-high-density lipoprotein-cholesterol (non-HDL-C) are also suitable parameters to assess cardiovascular risk and to guide lipid-lowering therapy. The advantage of the use of these variables is that they can be used in both the fasting and non-fasting state. In most cases, postprandial lipid profiles in combination with apo B are as useful as fasting lipid profiles for the differentiation between familial lipid disorders, such as heterozygous familial hypercholesterolemia, familial combined hyperlipidemia and familial hypertriglyceridemia. This article will address the interpretation, applications and limitations of a non-fasting lipid profile for daily clinical practice. © 2014 Elsevier Ireland Ltd. Source

Klop B.,Diabetes and Vascular Center | van de Geijn G.-J.M.,Sint Franciscus Gasthuis | Bovenberg S.A.,Diabetes and Vascular Center | van der Meulen N.,Diabetes and Vascular Center | And 7 more authors.
PLoS ONE | Year: 2013

Introduction:Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms.Methods:Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis.Results:Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80±0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57±0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56±0.94 a.u.) when compared to subjects with blood group A (0.89±1.15 a.u), blood group B (0.73±0.1.12 a.u.) or blood group AB (0.69±0.69 a.u.) (P-ANOVA = 0.002).Conclusion:Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant. © 2013 Klop et al. Source

Klop B.,Diabetes and Vascular Center | Elte J.W.F.,Diabetes and Vascular Center | Cabezas M.C.,Diabetes and Vascular Center
Nutrients | Year: 2013

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia. © 2013 by the authors; licensee MDPI, Basel, Switzerland. Source

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