Abstract:
BACKGROUND:Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (HCM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric HCM. METHODS:A total of 80 unrelated patients <21 y and 14 related members from eight families with HCM were genotyped for six variants associated with vascular endothelial growth factor A (VEGFA) downregulation, or hypoxia-inducible factor A (HIF1A) upregulation. Associations between risk genotypes and left-ventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with HCM and 20 patients without HCM. RESULTS:Age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged E-wave deceleration time (EWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial HCM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial HIF1A and transforming growth factor B1 (TGFB1) expression and increased endothelial-fibroblast transformation (P < 0.05). CONCLUSION:HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in HCM.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Alkon J,Friedberg MK,Manlhiot C,Manickaraj AK,Kinnear C,McCrindle BW,Benson LN,Addonizio LJ,Colan SD,Mital Sdoi
10.1038/pr.2012.126subject
Has Abstractpub_date
2012-12-01 00:00:00pages
583-92issue
6eissn
0031-3998issn
1530-0447pii
pr2012126journal_volume
72pub_type
杂志文章abstract:BACKGROUND:Current tools to predict the severity of respiratory syncytial virus (RSV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RSV-infected children. METHODS:Blood and nasopharyng...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2012.163
更新日期:2013-02-01 00:00:00
abstract::In dissociated whole brain cell cultures from newborn mice, we have previously shown that during glucose deprivation under normoxia, D-beta-hydroxybutyrate and oleic acid are increasingly used for energy production. We now asked whether this glucose dependency of the utilization of D-beta-hydroxybutyrate and oleic aci...
journal_title:Pediatric research
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doi:10.1203/00006450-198911000-00023
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abstract::Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance i...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199107000-00008
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abstract::Factors affecting bone turnover in premature infants are not entirely clear but certainly are different from those influencing bones of adults and children. To identify fetal and maternal factors that might influence bone turnover, we prospectively studied 50 infants (30 preterm and 20 full-term) born at Ain Shams Uni...
journal_title:Pediatric research
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更新日期:2005-05-01 00:00:00
abstract:BACKGROUND:Near-infrared spectroscopy is used in the assessment of regional splanchnic oxygen saturation (rsSO2), but solid reference values are scarce. We aimed to establish reference values of rsSO2 for preterm infants during the first week after birth, both crude and modeled based on predictors. METHODS:We included...
journal_title:Pediatric research
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abstract:BACKGROUND:The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the lit...
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journal_title:Pediatric research
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更新日期:1985-10-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章,撤回出版物
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abstract::Sarcoplasmic reticulum (SR) Ca release has been shown not to be the predominant mechanism responsible for excitation-contraction (E-C) coupling in fetal myocytes. However, most of the studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor ...
journal_title:Pediatric research
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abstract::Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pr...
journal_title:Pediatric research
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更新日期:2008-08-01 00:00:00
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journal_title:Pediatric research
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更新日期:1993-03-01 00:00:00
abstract::We have investigated the impaired secretion response of neonatal platelets. We compared the response of washed neonatal and adult platelets to thrombin and collagen, and to specific activators of calcium flux (inositol trisphosphate) and protein kinase C activation (oleoyl-acetyl glycerol). Neonatal platelets show no ...
journal_title:Pediatric research
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199303000-00022
更新日期:1993-03-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2016-07-01 00:00:00
abstract::The purpose of this study was to investigate the effect of constant light in a neonatal care unit on the development of the sleep-and-wakefulness rhythm in preterm infants. Two groups of infants (57 preterm infants without other complications and 58 healthy term infants) were prospectively studied over infancy by a da...
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更新日期:1993-02-01 00:00:00
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journal_title:Pediatric research
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更新日期:2009-11-01 00:00:00
abstract::Television viewing (TVV) is considered a contributing factor to the development of childhood obesity yet it is unclear whether obesity results, in part, from increased energy intake during TVV. The objective of this study was to determine the effect of TVV on food intake (FI) of boys at a meal and its effect on calori...
journal_title:Pediatric research
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doi:10.1203/pdr.0b013e3180536591
更新日期:2007-06-01 00:00:00
abstract::The developmental stages of each foregut organ are intimately linked to the development of the other foregut organs such that the ultimate function of any one foregut organ, such as the metabolic function of the liver, depends on organizational changes associated with the maturation of multiple foregut organs. These c...
journal_title:Pediatric research
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更新日期:2014-01-01 00:00:00
abstract::We compared sex-specific growth attainment of a population-based cohort of 147/166 (89%) extremely low birthweight (ELBW < 1000 g) and 131/145 (90%) sociodemographically comparable normal birthweight (NBW) cohort at young adulthood, and examined the pattern of growth trajectories and correlates of growth at ages 1, 2,...
journal_title:Pediatric research
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doi:10.1203/01.pdr.0000246201.93662.8e
更新日期:2006-12-01 00:00:00
abstract::We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10-870 and 10-940/microL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 +/- 0.9 and 1.9 +/- 1....
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199501000-00011
更新日期:1995-01-01 00:00:00
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更新日期:2005-05-01 00:00:00
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journal_title:Pediatric research
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doi:10.1203/00006450-199409000-00023
更新日期:1994-09-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318179957d
更新日期:2008-08-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:
更新日期:1981-05-01 00:00:00
abstract::We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199001000-00018
更新日期:1990-01-01 00:00:00
abstract::Premature rabbits delivered by cesarean section at 28 d of gestation were each given intratracheally 75 mg/kg of radiolabeled preparation of either natural rabbit surfactant, natural calf surfactant, or surfactant-TA. Each newborn rabbit was ventilated for up to 6 h in a ventilator-plethysmograph with individual adjus...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198904000-00024
更新日期:1989-04-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197904000-00002
更新日期:1979-04-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198907000-00002
更新日期:1989-07-01 00:00:00
abstract::Endothelin (ET)-1 is a potent vasoconstrictor peptide that modulates basal pulmonary vascular resistance (PVR) in the normal ovine fetus and contributes to high PVR after chronic intrauterine pulmonary hypertension. Although high PVR is present in premature lambs with severe hyaline membrane disease (HMD), whether ET-...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199808000-00006
更新日期:1998-08-01 00:00:00
abstract::The functional activity of naturally acquired IgG and IgM with specificity for the capsular polysaccharide of type III, group B Streptococcus (III-GBS) was compared. Sera collected during convalescence from 14 infants who had developed specific antibodies following III-GBS infection were employed for separation of IgG...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198801000-00007
更新日期:1988-01-01 00:00:00