Search results for "LOCI"
showing 10 items of 1277 documents
Exome chip association study excluded the involvement of rare coding variants with large effect sizes in the etiology of anorectal malformations
2019
IntroductionAnorectal malformations (ARM) are rare congenital malformations, resulting from disturbed hindgut development. A genetic etiology has been suggested, but evidence for the involvement of specific genes is scarce. We evaluated the contribution of rare and low-frequency coding variants in ARM etiology, assuming a multifactorial model.MethodsWe analyzed 568 Caucasian ARM patients and 1,860 population-based controls using the Illumina Human Exome Beadchip array, which contains >240,000 rare and low-frequency coding variants. GenomeStudio clustering and calling was followed by re-calling of 'no-calls' using zCall for patients and controls simultaneously. Single variant and gene-bas…
Changes of the ratio between myelin thickness and axon diameter in human developing sural, femoral, ulnar, facial, and trochlear nerves
1988
Previous studies on sural nerves were extended to human femoral, ulnar, facial and trochlear nerves. As asynchronous development of axon diameter and myelin sheath thickness was noted in all nerves studied. Whereas axons reach their maximal diameter by or before 5 years of age, maximal myelin sheath thickness is not attained before 16-17 years of age, i.e., more than 10 years later. The slope of the regression lines for the ratio between axon diameter and myelin thickness is significantly steeper in older than in younger individuals; it also differs if small and large fibers with more or less than 50 myelin lamellae are evaluated separately. The number of Schmidt-Lanterman incisures during …
Frequency and characterization of DNA methylation defects in children born SGA
2012
Various genes located at imprinted loci and regulated by epigenetic mechanisms are involved in the control of growth and differentiation. The broad phenotypic variability of imprinting disorders suggests that individuals with inborn errors of imprinting might remain undetected among patients born small for gestational age (SGA). We evaluated quantitative DNA methylation analysis at differentially methylated regions (DMRs) of 10 imprinted loci (PLAGL1, IGF2R DMR2, GRB10, H19 DMR, IGF2, MEG3, NDN, SNRPN, NESP, NESPAS) by bisulphite pyrosequencing in 98 patients born SGA and 50 controls. For IGF2R DMR2, methylation patterns of additional 47 parent pairs and one mother (95 individuals) of patie…
Thoracic Aortic Intima-Media Thickness in Preschool Children Born Small for Gestational Age
2018
To assess thoracic aortic intima-media thickness (aIMT) as a marker of thoracic aortic remodeling in children born small for gestational age (SGA).We assessed thoracic aIMT, carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) in 239 patients (117 SGA; 122 appropriate for gestational age controls) age 6-8 years. Each SGA participant was matched 1:1 based on sex, gestational age, and birth date. Thoracic aIMT was determined by 2-dimensional transthoracic echocardiography.SGA children showed a significant increase in both aIMT (0.89 mm [0.12] vs 0.79 mm [0.11], P .001) and cIMT (.50 mm [0.05] vs 0.49 mm [0.04], P .001) compared with appropriate for gestational age controls, …
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
2013
Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locu…
Nitric oxide modulates cerebral blood flow stimulation by acetazolamide in the rat cortex: a laser Doppler scanning study
2001
Abstract The involvement of nitric oxide (NO) in cerebral blood flow (CBF) stimulation by acetazolamide was studied in anaesthetised, mechanically ventilated Wistar rats. CBF was monitored by laser Doppler scanning. Acetazolamide induced a long-lasting significant rCBF-increase. Application of N G -Nitro- l -arginine (L-NNA), an inhibitor of all NO synthetases (NOS), prevented CBF stimulation by acetazolamide. Continuous infusion of the exogenous NO donor SIN-1 (3-morpholinosydnonimine) suppressed L-NNA induced increases of mean arterial blood pressure without effect on rCBF in comparison to baseline. Additional acetazolamide injection then again caused a significant increase of rCBF in spi…
Takotsubo Cardiomyopathy: One More Angiographic Evidence of Microvascular Dysfunction
2017
Background Takotsubo cardiomyopathy (TC) aetiology has not been completely understood yet. One proposed pathogenic mechanism was coronary microvascular dysfunction (MVD). This study compared coronary flow and myocardial perfusion in patients with TC, microvascular angina (MVA), and a control group (CG). Methods Out of 42 consecutive patients presented to our centre with TC from 2013 to 2017; we retrospectively selected 27 patients. We compared them with a sex- and age-matched group of 27 MVA cases and 27 patients with normal coronary arteries (CG). The flow was evaluated in the three coronary arteries as TIMI flow and TIMI frame count (TFC). Myocardial perfusion was studied with Blush-Score…
Influence of competition on performance factors in under-19 soccer players at national league level.
2020
The aim of this study was to analyse and quantify the acute effects of competition on several performance factors in under-19 male soccer players. To this end, 198 national league players (17.56 ± 0.78 years) performed various tests to measure jump capacity, kicking velocity and sprint times immediately pre-match (T1), at half-time (T2) and post-match (T3). Tests included kicking the ball to measure ball velocity (KICK), sprinting for 40 meters, timing the first 30 meters (30mACCEL), the last 10 meters (10mACCEL) and the total distance (40mACCEL), and performing countermovement jumps (CMJ). For subsequent analysis, the sample was divided into 5 playing positions: goalkeepers (n = 24), defen…
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
2012
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral…
Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial
2012
Aims High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular (CV) events and thus an attractive therapeutic target. However, in spite of marked elevations in HDL-C, the first cholesterol transport protein (CETP) inhibitor torcetrapib raised blood pressure (BP), impaired endothelial function, and increased CV mortality and morbidity. Dalcetrapib is a novel molecule acting on CETP with a different chemical structure to torcetrapib. As HDL stimulates nitric oxide (NO), suppresses inflammation, and exerts protective CV effects, we investigated the effects of dalcetrapib on endothelial function, blood pressure, inflammatory markers, and lipids in patients with, o…