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Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
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Endothelin modulation of neuroeffector transmission in rat and guinea pig vas deferens 总被引:4,自引:0,他引:4
N P Wiklund A Ohlén C U Wiklund P Hedqvist L E Gustafsson 《European journal of pharmacology》1990,185(1):25-33
The effects of endothelin-1 (human, porcine) on contractions induced by transmural nerve stimulation, exogenous ATP or noradrenaline, and on the release of [3H]noradrenaline were studied in guinea pig and rat vas deferens. Endothelin enhanced nerve-induced contractile responses, increased basal muscle tone and increased the contractile response to exogenous ATP in both guinea pig and rat vas deferens. Endothelin did not affect the contractile responses to exogenous noradrenaline. The calcium channel blocker felodipine antagonized the stimulating effects of endothelin in the rat vas deferens, whereas blockade of lipoxygenase and cyclooxygenase pathways by a combination of BW 755C and indomethacin was without effect. In rat vas deferens preparations preincubated with [3H]noradrenaline, endothelin inhibited the 3H overflow induced by transmural stimulation, although the contractile responses were enhanced by endothelin. Pretreatment with forskolin or felodipine did not abolish the endothelin inhibition of radiotracer overflow. In conclusion, endothelin can modulate adrenergic and purinergic neuroeffector transmission in both guinea pig and rat vas deferens via inhibitory prejunctional and stimulant postjunctional mechanisms. The stimulant postjunctional effect seemed to predominate in our experiments. 相似文献
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Complications following combined transrectal aspiration and core biopsy of the prostate 总被引:2,自引:0,他引:2
O Gustafsson U Norming C R Nyman M Ohstr?m 《Scandinavian journal of urology and nephrology》1990,24(4):249-251
Ultrasound guided biopsy of the prostate with fine needle (22G) as well as trucut needle (18G) was performed in 145 patients with a suspicion of prostate cancer. After three weeks all patients were interviewed about complications associated with the biopsy. Hematuria and/or hemospermia occurred in 2/3 of the patients. None of the hemorrhages was severe and all ceased spontaneously. E. coli infection of the urinary tract occurred in 9 cases (6.2%). Five of the infections caused high fever and necessitated hospital care with parenteral antibiotics for 1 to 8 days. The patients with infection had no signs of immunological defects by which they might have been identified before the biopsy. As a consequence of these observations we now use prophylactic antibiotics when core biopsy of the prostate is performed transrectally. 相似文献
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The effect of cooking time on mutagenic activity in crust, pan residue and smoke from pan-broiled pork patties was studied in the Ames Salmonella mutagenicity test system. The effect on mutagenicity of reheating the cooked patties and of keeping them warm was also studied. The meat was broiled at 200 degrees C for various times between 2 and 10 min. Broiled meat was reheated up to 5 times at 200 degrees C, each time to a centre temperature of 70 degrees C. Reheating was also performed in a microwave oven for 2 min and in an electric oven at 200 degrees C for 10 min. In addition, broiled patties were kept warm at 60 degrees C in an incubator for up to 9 hr. The mutagenic activity increased rapidly in all fractions except the volatile phase over the first 6 min of cooking, after which time only a slight increase was seen. At cooking times below 4 min no mutagenic activity was detected in the smoke. Reheating or keeping the meat warm for up to 9 hr had very little effect on the mutagenic activity of the meat. Reversed-phase high-performance liquid chromatography mutagenicity profiles of the aerosol, crust and pan-residue extracts showed no major qualitative differences in samples cooked at different times. It is concluded that during pan broiling at 200 degrees C the major part of the mutagenic activity is formed during the first 6 min of cooking. Reheating the meat or keeping it warm does not significantly affect the mutagenic activity. No major additional mutagens are formed during continued heating for up to 25 min. 相似文献
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Stroke rehabilitation is an area of practice that many occupational therapists encounter during their career. The literature promotes a wide range of management techniques and support devices for people who have a stroke-affected upper limb, but little is known about the validity of those that occupational therapists actually use in practice. A questionnaire was sent to occupational therapists working in Queensland and northern New South Wales facilities (n = 35), in which adults with a stroke were likely to be treated. Eighteen respondents answered questions about the management techniques and support devices used in their facility, and their perception of the benefit of these devices in the reduction of hemiplegic shoulder pain. Results are discussed with reference to evidence-based practice and indicate an urgent need for the collation and dissemination of the best current evidence available for the management techniques and support devices used in this area, as well as further research to extend this evidence. 相似文献
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J. Gong B. D. Rawal C. F. Högman MD G. N. Vyas B. Nilsson and I. Gustafsson 《Vox sanguinis》1994,66(3):166-170
We report studies on the complement sensitivity of four strains of Yersinia enterocolitica , serotypes O:3, O:9, O:5,27, and O:20, isolated from blood units involved in transfusion fatalities. Complement in fresh CPD plasma killed Y. enterocolitica within 4 h at 22°C in 100% of the experiments. The bactericidal action was serotype and complement activation pathway dependent. Both classic and alternate pathways seemed to be active, but the latter to a lesser degree. When the classic pathway was blocked by chelation of Ca2+ no complete killing was obtained. Complement did not enhance or condition Yersinia for leucocyte filter retention. Direct removal of Yersinia by filtration was also related to serotype; all strains were reduced by filtration in heat-inactivated plasma, and all except serotype O:5,27 were reduced in Ca2+ -chelated plasma. Our findings may explain why plasma products and platelet concentrates are rarely involved in Yersinia sepsis related to transfusion. 相似文献