Publications by authors named "David Kirchner"

Introduction: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.

Objective: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.

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Background: The metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth might influence fetal growth and birth anthropometry. The objective was to examine how maternal plasma and umbilical cord plasma metabolites are associated with newborn anthropometric measures, a known predictor of future health outcomes.

Methods: Pregnant women between 24 and 28 weeks of gestation were recruited as part of a prospective cohort study.

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Background/objectives: Excessive gestational weight gain (GWG) and pre-pregnancy obesity affect a significant portion of the US pregnant population and are linked with negative maternal and child health outcomes. The objective of this study was to explore associations of pre-pregnancy body mass index (pBMI) and GWG with longitudinally measured maternal urinary metabolites throughout pregnancy.

Subjects/methods: Among 652 participants in the New York University Children's Health and Environment Study, a longitudinal pregnancy cohort, targeted metabolomics were measured in serially collected urine samples throughout pregnancy.

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Background: Metabolomics is a promising method to investigate physiological effects of chemical exposures during pregnancy, with the potential to clarify toxicological mechanisms, suggest sensitive endpoints, and identify novel biomarkers of exposures.

Objective: Investigate the influence of chemical exposures on the maternal plasma metabolome during pregnancy.

Methods: Data were obtained from participants (n = 177) in the New Hampshire Birth Cohort Study, a prospective pregnancy cohort.

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Background: Choline deficiency has numerous negative health consequences; although the preponderance of the US population consumes less than the recommended Adequate Intake (AI), clinical assessment of choline status is difficult. Further, several pathways involved in primary metabolism of choline are estrogen-sensitive and the AI for premenopausal women is lower than that for men.

Objectives: We sought to determine whether in vivo magnetic resonance spectroscopy (MRS) of liver and/or isotope-dilution MS of plasma could identify biomarkers reflective of choline intake (preregistered primary outcomes 1 and 2, secondary outcome 1).

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High levels of cholesterol, especially as low-density lipoprotein (LDL), are a well-known risk factor for atherosclerotic-related diseases. The key atherogenic property of LDL is its ability to form atherosclerotic plaque. Proprotein convertase subtilisin/kexin-9 (PCSK9) is an indirect regulator of plasma LDL levels by controlling the number of LDL receptor molecules expressed at the plasma membrane, especially in the liver.

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Ceramides are important participants of signal transduction, regulating fundamental cellular processes. Here we report the mechanism for activation of p53 tumor suppressor by C-ceramide. C-ceramide tightly binds within the p53 DNA-binding domain (K ~ 60 nM), in close vicinity to the Box V motif.

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Background: Studies integrating transcriptomic data with proteomic data can illuminate the proteome more clearly than either separately. Integromic studies can deepen understanding of the dynamic complex regulatory relationship between the transcriptome and the proteome. Integrating these data dictates a reliable mapping between the identifier nomenclature resultant from the two high-throughput platforms.

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Objective: The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.

Methods: A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types.

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Objective: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.

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