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Sökning: WFRF:(Tomlinson G.)

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361.
  • O'Mara, TA, et al. (författare)
  • Identification of nine new susceptibility loci for endometrial cancer
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3166-
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
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365.
  • Spaak, J, et al. (författare)
  • Dose-related effects of red wine and alcohol on heart rate variability
  • 2010
  • Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 298:6, s. H2226-H2231
  • Tidskriftsartikel (refereegranskat)abstract
    • In healthy subjects a standard drink of either red wine (RW) or ethanol (EtOH) has no effect on muscle sympathetic nerve activity or on heart rate (HR), whereas two drinks increase both. Using time- and frequency-domain indexes of HR variability (HRV), we now tested in 12 subjects (24–47 yr, 6 men) the hypotheses that 1) this HR increase reflects concurrent dose-related augmented sympathetic HR modulation and 2) RW with high-polyphenol content differs from EtOH in its acute HRV effects. RW, EtOH, and water were provided on 3 days, 2 wk apart according to a randomized, single-blind design. Eight-minute segments were analyzed. One alcoholic drink increased blood concentrations to 36 ± 2 mg/dl (mean ± SE), and 2 drinks to 72 ± 4 (RW) and 80 ± 2 mg/dl (EtOH). RW quadrupled plasma resveratrol ( P < 0.001). HR fell after both water drinks. When compared with respective baselines, one alcoholic drink had no effect on HR or HRV, whereas two glasses of both increased HR (RW, +5.4 ± 1.2; and EtOH, +5.7 ± 1.2 min−1; P < 0.001), decreased total HRV by 28–33% ( P < 0.05) and high-frequency spectral power by 32–42% (vagal HR modulation), and increased low-frequency power by 28–34% and the ratio of low frequency to high frequency by 98–119% (sympathetic HR modulation) (all, P ≤ 0.01). In summary, when compared with water, one standard drink lowered time- and frequency-domain markers of vagal HR modulation. When compared with respective baselines, two alcoholic drinks increased HR by diminished vagal and augmented sympathetic HR modulation. Thus alcohol exerts dose-dependent HRV responses, with RW and EtOH having a similar effect.
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366.
  • Spaak, J, et al. (författare)
  • Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter
  • 2008
  • Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 294:2, s. H605-H612
  • Tidskriftsartikel (refereegranskat)abstract
    • The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24–47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 ± 2 and 39 ± 2 mg/dl, respectively, and two drinks to 72 ± 4 and 83 ± 3 mg/dl, respectively. Wine quadrupled plasma resveratrol ( P < 0.001) and increased catechin ( P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 ± 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 ± 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 ± 0.3 l/min) and wine (+1.2 ± 0.3 l/min) ( P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9–10 bursts/min ( P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks ( P < 0.001). No beverage augmented, and the second wine dose attenuated ( P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.
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  • Resultat 361-370 av 379

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