Papers by Robert de Jonge
Arthritis Research & Therapy, 2019
Journal of Reproductive Immunology, 2016
Pregnancies complicated by preeclampsia (PE) are characterised by an enhanced maternal and fetal ... more Pregnancies complicated by preeclampsia (PE) are characterised by an enhanced maternal and fetal inflammatory response with increased numbers of leukocytes in maternal peripheral blood. The impact of PE on newborn umbilical cord blood cell (UCBC) populations however, has been scarcely studied. We hypothesise that PE deranges fetal haematopoiesis and subsequently UCBC populations. Therefore, the objective of this study was to investigate newborn umbilical cord blood cell populations in early-(EOPE) and late-onset PE (LOPE). A secondary cohort analysis in The Rotterdam Periconceptional Cohort was conducted comprising 23 PE cases, including 11 EOPE and 12 LOPE, and 195 controls, including 153 uncomplicated and 23 fetal growth restriction-and 19 preterm birth complicated controls. UCBC counts and differentials were quantified by flow cytometry and analysed as main outcome measures. Multivariable regression analysis revealed associations of EOPE with decreased leucocyte-(monocytes, neutrophils, eosinophils, immature granulocytes) and thrombocyte counts and increased NRBC counts (all p < 0.05). EOPE remained associated with neutrophil-(-0.92, 95%CI −1.27,−0.57, p < 0.001) and NRBC counts (1.11, 95%CI 0.27,1.95, p = 0.010) after adjustment for gestational age and birth weight. LOPE did not reveal any significant association. We conclude that derangements of fetal haematopoiesis, in particular of neutrophil-and NRBC counts, are associated with EOPE only, with a potential impact for future health of the offspring. This heterogeneity in UCBC should be considered as confounder in epigenetic association studies examining EOPE.
Clinical Chemistry and Laboratory Medicine (CCLM), 2016
The aim of this study was to compare different analytical methods that are currently in use in th... more The aim of this study was to compare different analytical methods that are currently in use in the Netherlands for the measurement of whole blood vitamin B6.This method comparison study consisted of two separate parts. (1) Four laboratories participated in a pilot study in which the commercial Chromsystems and INstruchemie method, and a laboratory developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and HPLC method were compared. Sixty-nine frozen whole blood samples and six lyophilized whole blood samples were used for comparison. (2) In the nationwide part of the study, 49 laboratories participated in the analysis of three identical sets of two whole blood samples of which one set was freshly analyzed, one set was analyzed after storage at −20 °C and one set was analyzed after lyophilization.In both parts of the study, the HPLC and LC-MS/MS methods showed equivalent results for all sample types tested. The Chromsystems method showed a positive bias of 45% (pi...
Therapeutic Drug Monitoring, 2012
The Journal of Rheumatology, 2014
Objective.Low-dose methotrexate (MTX) is the anchor drug in the treatment for rheumatoid arthriti... more Objective.Low-dose methotrexate (MTX) is the anchor drug in the treatment for rheumatoid arthritis (RA). Response to MTX is related to the intracellular MTX-polyglutamate (MTX-PG) levels and little is known about its determinants. We aimed to define the determinants of erythrocyte MTX-PG concentrations in 2 prospective cohorts of patients with RA.Methods.Patients with RA treated with MTX from 2 longitudinal cohorts were included: 93 from the MTX-R study (Rotterdam, the Netherlands derivation cohort), and 247 from the treatment in Rotterdam Early Arthritis Cohort study (validation cohort). MTX-PG concentrations were measured at 3 months of treatment using liquid chromatography/mass spectrometry. The MTX-PG were used as outcome measure. Various sociodemographic, clinical, biochemical, and genetic factors were assessed at baseline. Associations with MTX-PG levels were analyzed using multivariate regression analysis.Results.Age was positively associated with MTX-PG1 (stβ 0.23, p = 0.033...
The Pharmacogenomics Journal, 2014
New England Journal of Medicine, 2004
Journal of Molecular and Cellular Cardiology, 1998
Journal of Chromatography B, 2012
Vitamin B6 is a cofactor in numerous biologic processes that include gluconeogenesis, neurotransm... more Vitamin B6 is a cofactor in numerous biologic processes that include gluconeogenesis, neurotransmitter synthesis and amino acid metabolism. The aim of this study was to develop a method to measure the concentration of the biologically active form of vitamin B6 (pyridoxal-5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-phosphate, PLP) in whole blood with stable isotope dilution LC-ESI-MS/MS and compare this new procedure with an established HPLC method based on derivatization of pyridoxal-5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-phosphate. 50 μl of stable isotope (PLP-d3) was added to 250 μl of sample, followed by deproteinization with 10% trichloroacetic acid. After centrifugation, 20 μl of the supernatant was injected into the LC-ESI-MS/MS. Reversed phase chromatography was performed on a UPLC system, using a Waters™ Symmetry C18 column, with a gradient of 0.1% formic acid in methanol. PLP was measured on a tandem MS with a mass transition of 247.8&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;149.8 in the positive ion mode with a collision energy of 14 eV. The chromatographic run lasted 4 min. The method was linear from 4 to 8000 nmol/l. The intra-day and inter-day precision ranged between 1.7-2.8% and 3.0-4.1%, respectively. The mean absolute matrix-effect was 99.3% [97-102%]. The relative matrix-effect was 98.8%. The mean recovery was 98% [89-103%]. The lower limit of quantification was 4 nmol/l. The comparison of the LC-ESI-MS/MS method with our current HPLC method yielded the following equation: LC-ESI-MS/MS=1.11 [confidence interval, CI: 1.03-1.20] × HPLC+4.6 [CI: -1.3 to 11.0] (r²=0.94). This LC-ESI-MS/MS based method is characterized by simple sample processing and a short run time. The comparison with the current HPLC method is excellent although a significant proportional bias was detected. To conclude, the LC-ESI-MS/MS method is an appropriate method to determine PLP in whole blood.
Journal of Bone and Mineral Research, 2007
The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate a... more The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk.Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ≥55 y...
Bioanalysis, 2011
A new analytical MS method using isotope dilution combined with MALDI-triple quadrupole MS/MS has... more A new analytical MS method using isotope dilution combined with MALDI-triple quadrupole MS/MS has been developed and validated for the determination of methotrexate and 7-hydroxymethotrexate in plasma. Methotrexate, methotrexate-d3, 7-hydroxymethotrexate and 7-hydroxymethotrexate-d3 were monitored by selected reaction monitoring using the transitions m/z 455.2→308.2, 458.2→311.2, 471.2→324.2 and 474.2→327.2 for methotrexate, methotrexate-d3, 7-hydroxymethotrexate and 7-hydroxymethotrexate-d3, respectively.
Rapid communications in mass spectrometry : RCM, Jan 30, 2011
A new ultrafast quantitative and high-throughput mass spectrometric method using matrix-assisted ... more A new ultrafast quantitative and high-throughput mass spectrometric method using matrix-assisted laser desorption/ionization triple quadrupole tandem mass spectrometry has been developed and validated for determination of intracellular erythrocyte concentrations of the antifolate drug methotrexate (MTX) and its polyglutamate metabolites. The method consists of a solid-phase extraction of MTX and MTX-polyglutamate metabolites from deproteinized erythrocyte lysates spiked with aminopterin as internal standard. The newly developed method was validated according to the most recent FDA guidelines on linearity, recovery, within-run and between-run accuracy and precision and stability of the analytes. The low limit of quantification (LLOQ) was 10 nmol/L for all analytes while the limit of detection (LOD) determined at a signal-to-noise (S/N) ratio = 3:1 in drug- free erythrocyte lysate was on average 0.3 nmol/L. After validation, the new method was used in the measurement of intracellular ...
European Journal of Pharmacology, 2001
We tested whether ischemic preconditioning of the rat heart is mediated by reduced glycogenolysis... more We tested whether ischemic preconditioning of the rat heart is mediated by reduced glycogenolysis during ischemia, an event triggered by adenosine A1 receptor activation. Rat hearts (n=40) were studied with [31P] and [13C] nuclear magnetic resonance (NMR) spectroscopy, using the Langendorff perfusion technique (5.5 mM [1-13C]glucose, 10 U/l insulin). In parallel experiments, hearts (n=43) were freeze-clamped at different time-points throughout the protocol. They were subjected to either ischemic preconditioning (PC), PC in the presence of 50 microM adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (SPT), or intermittent infusion of 0.25 microM adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA). After 30 min ischemia and reperfusion, recovery of heart ratexpressure product was improved in hearts treated with preconditioning (33+/-13%) or CCPA (58+/-14%) compared with the SPT and ischemic control (IC) groups, which both failed to recover (P&amp;amp;amp;amp;lt;0.05). CCPA administration induced a 58% increase in pre-ischemic [13C]glycogen (P&amp;amp;amp;amp;lt;0.05 vs. all groups). In the PC and SPT groups, [13C]glycogen decreased by 25 and 47%, respectively (P&amp;amp;amp;amp;lt;0.05) due to the short bouts of ischemia, resulting in lower pre-ischemic glycogen compared to ischemic control and CCPA hearts (P&amp;amp;amp;amp;lt;0.05). The rate of [13C]glycogen utilization during the first 15 min of ischemia (in micromol/min g wwt) was not statistically different between IC (0.42+/-0.03), PC (0.30+/-0.04), and CCPA (0.38+/-0.05) hearts, but was reduced in SPT hearts (0.24+/-0.05; P&amp;amp;amp;amp;lt;0.05). Total glycogen depletion during 30-min ischemia was reduced in PC hearts (0.61 mg/g wwt) compared to IC (1.84 mg/g wwt) and CCPA (1.75 mg/g wwt) hearts; SPT did not block reduced glycogenolysis during ischemia in PC hearts (0.77 mg/g wwt vs. IC). This study adds further strong evidence that in rat hearts, adenosine is involved in ischemic preconditioning. However, protection is unrelated to pre-ischemic glycogen levels and glycogenolysis during ischemia.
European Journal of Clinical Investigation, 2010
Coronary Artery Disease, 2006
, considers the reporting of the research by Feringa et al. [1] to have been negligent and scient... more , considers the reporting of the research by Feringa et al. [1] to have been negligent and scientifically incorrect according to two criteria: the inclusion and exclusion criteria reported in the publication were not applied consistently, with the result that the patient population actually studied differs in material ways from the published description; and, there are material differences between the source documentation (the patients' dossier), the case record form used in the study, the study database, and the publication. For this reason the article by Feringa et al. [1] is retracted from publication.
Clinica Chimica Acta, 2005
The most common 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C/844ins68 in... more The most common 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C/844ins68 in cis double mutation in the cystathionine beta synthase (CBS) gene probably is non-pathogenic because the 68-bp insertion eliminates the 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C mutation due to alternative splicing. However, allele frequency and effects of the isolated 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C mutation are unclear. DNA was isolated from 500 volunteers and used directly for PCR-RFLP of CBS gene exon-8. A new primer design was developed to create annealing sites upstream and downstream of exon-8 for forward and reverse primers, respectively. The design was made to exclude sequence homology of the forward primer with the insert fragment and to introduce an internal Bsr1 digestion site. A new 9276G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A mutation was found in intron 8. Because of this mutation, an extra Bsr1 digestion site is created in intron 8. In Caucasian volunteers, the following allele frequencies were found: 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C=0.2%, 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C/844ins68=10.2%, and 9276G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A=0.2%. The developed PCR-RFLP method is able to detect the 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C mutation, the 833T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C/844ins68 polymorphism as well as a new 9276G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A mutation in intron 8. Further study should explore the effect of the isolated 9276G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A mutation.
Bone, 2012
An elevated level of plasma homocysteine (Hcy) is a known risk factor for osteoporotic fractures.... more An elevated level of plasma homocysteine (Hcy) is a known risk factor for osteoporotic fractures. In addition, Hcy is related to DNA-methylation metabolism. To determine whether the association between Hcy and fractures is explained by an altered methylation capacity, we investigated the associations between levels of s-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and fracture risk. We studied 503 females aged 55 years and over from the Rotterdam Study (RS) in whom plasma Hcy, SAM and SAH levels were measured. Bone mineral density (BMD) at the hip was assessed using DXA. Incident fractures were recorded over a mean period of 7.0 years. Cox proportional hazards analysis and linear regression were used to assess relationships between plasma metabolite levels, incident osteoporotic fractures and BMD. Over a total of 3502 person-years of follow-up, 103 subjects sustained at least one osteoporotic fracture. Whereas incidence of osteoporotic fractures was associated with quartiles of Hcy (p=0.047), it was not associated with quartiles of SAM, SAH or SAM/SAH-ratio (all p for trend&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.6). Stepwise linear regression showed that SAM/SAH-ratio, but not Hcy, was independently associated with hip BMD (β=0.073, p=0.025). Since SAM, SAH and SAM/SAH-ratio were not associated with osteoporotic fractures, alterations in methylation capacity most likely do not appear to be an important factor in the association between Hcy and fractures.
Blood, 2005
We studied whether common polymorphisms in genes involved in folate metabolism affect methotrexat... more We studied whether common polymorphisms in genes involved in folate metabolism affect methotrexate (MTX) sensitivity. Ex vivo MTX sensitivity of lymphoblasts obtained from pediatric patients with acute lymphoblastic leukemia (ALL; n = 157) was determined by the in situ thymidylate synthase inhibition assay after either continuous (21 hours; TSI50, cont) or short-term (3 hours; TSI50, short) MTX exposure. DNA was isolated from lymphoblasts obtained from cytospin slides. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR 677C>T, MTHFR 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC 80G>A) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time PCR. Patients with the MTHFR 1298AC variant or t...
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Papers by Robert de Jonge