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排序方式: 共有1423条查询结果,搜索用时 171 毫秒
1.
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
2.
D A Lythall D G Gibson S S Kushwaha M S Norell A G Mitchell C J Ilsley 《Heart (British Cardiac Society)》1992,67(5):368-376
OBJECTIVE--This study investigated the changes in regional myocardial ultrasonic backscatter, measured as myocardial echo amplitude, that occur during reversible myocardial ischaemia in humans. DESIGN--Left anterior descending coronary angioplasty was used to produce reversible myocardial ischaemia in human subjects. Regional myocardial echo amplitude was studied in the interventricular septum and left ventricular posterior free wall before, during, and after coronary occlusion with the angioplasty balloon. Wall motion analysis of the left ventricle was performed from simultaneous cross sectional echocardiographic imaging. Patients were studied prospectively. PATIENTS--Six patients (mean age 56 (SD 11), range 46 to 69 years) with single vessel, left anterior descending coronary artery stenoses, were investigated during elective coronary angioplasty. A total of 11 balloon inflations were studied. SETTING--All patient studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. INTERVENTIONS--Angioplasty was performed by the usual procedure at Harefield Hospital for elective coronary angioplasty. All routine medication including beta blockers and calcium antagonists were continued. Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in three the second, in two the third, and in one each the fourth and fifth inflations. Echo amplitude and cross sectional echo-cardiographic studies were recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series) mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph system with 45 dB logarithmic grey scale compression. MAIN OUTCOME MEASURES--Regional echo amplitude was examined in four regions of the left ventricle--namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive end diastolic and end systolic frames were analysed and cyclic variation was determined as the difference between the level of echo amplitude at end diastole and at end systole. Measurements were made before balloon inflation, at peak inflation, and after balloon deflation. Regional wall motion and systolic wall thickening were analysed qualitatively. RESULTS--Before balloon inflation, cyclic variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1) dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0) dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of severe hypokinesis or akinesis in the mid-septum. No significant changes in echo amplitude occurred in the three other regions examined. Changes were completely reversed after balloon deflation. CONCLUSIONS--These results suggest a causal relation between occlusion of the supplying coronary artery and blunting of myocardial echo amplitude cyclic variation. It is suggested that balloon occlusion produced myocardial ischaemia. The resultant impairment of myocardial contraction then caused a blunting of cyclic variation in echo amplitude. The results of this study provide further data about the ability of quantitative studies of ultrasonic backscatter to identify alterations in the myocardium during injury. 相似文献
3.
4.
Adinarayana Andukuri Will P. Minor Meenakshi Kushwaha Joel M. Anderson Ho-Wook Jun 《Nanomedicine : nanotechnology, biology, and medicine》2010,6(2):289-297
The goal of this study is to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles (PAs) through a solvent evaporation technique. Three PAs, one containing the Tyr-Ile-Gly-Ser-Arg (YIGSR) ligand, the second containing the Val-Ala-Pro-Gly (VAPG) ligand, and a third without cell adhesive ligands, were developed. Cell adhesion and spreading were evaluated by a PicoGreen-DNA assay and live/dead assay, respectively. Our results show that PA-YIGSR significantly enhances HUVEC adhesion (26,704 ± 2708), spreading (84 ± 8%), and proliferation (50 ± 2%) compared with that of other PAs. PA-VAPG and PA-YIGSR showed significantly greater AoSMC adhesion compared with that of PA-S. PA-VAPG also showed significantly greater spreading of AoSMCs (63 ± 11%) compared with that of other PAs. Also, all the PAs showed significantly reduced platelet adhesion compared with that of collagen I (control). These findings would facilitate the development of novel vascular grafts, heart valves, and cell-based therapies for cardiovascular diseases.From the Clinical EditorThe goal of this study was to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles through a solvent evaporation technique. The findings are expected to facilitate the development of novel vascular grafts, heart valves, and cell based therapies for cardiovascular diseases. 相似文献
5.
Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates 下载免费PDF全文
The present studies were conducted to determinewhether a synthetic truncated apoC-I peptide thatinhibits CETP activity in baboons would raise plasmaHDL cholesterol levels in nonhuman primates with lowHDL levels. We used 2 cynomolgus monkeys and 3baboons fed a cholesterol- and fat-enriched diet. Incynomolgus monkeys, we injected synthetic truncatedapoC-I inhibitor peptide at a dose of 20mg/kgand, in baboons, at doses of 10, 15, and 20mg/kgat weekly intervals. Blood samples were collected 3times a week and VLDL + LDL and HDL cholesterolconcentrations were measured. In cynomolgus monkeys,administration of the inhibitor peptide caused arapid decrease in VLDL + LDL cholesterolconcentrations (30%–60%) and an increase in HDLcholesterol concentrations (10%–20%). VLDL + LDLcholesterol concentrations returned to baselinelevels in approximately 15days. In baboons,administration of the synthetic inhibitor peptidecaused a decrease in VLDL + LDL cholesterol (20%–60%)and an increase in HDL cholesterol (10%–20%). VLDL+ LDL cholesterol returned to baseline levels byday 21, whereas HDL cholesterol concentrationsremained elevated for up to 26days. ApoA-Iconcentrations increased, whereas apoE andtriglyceride concentrations decreased. Subcutaneousand intravenous administrations of the inhibitorpeptide had similar effects on LDL and HDLcholesterol concentrations. There was no change inbody weight, food consumption, or plasma IgGlevels of any baboon during the study. Thesestudies suggest that the truncated apoC-I peptide canbe used to raise HDL in humans. 相似文献
6.
Fernandes Priyanka Wang Karina Timmerman Jason Reyes Angela Holmes Faye Olaleye Omonike A. Salihu Hamisu M. Moerchen Victoria A. Belcher Harolyn M. E. Copeland-Linder Nikeea Noble Charlotte A. Vamos Cheryl A. Armstrong Anna Waters Catrina R. Long-White Deneen Brown Claudia Reddy Madhavi M. Kuo Alice 《Maternal and child health journal》2022,26(7):1415-1423
Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from... 相似文献
7.
Priyanka Sharma Guojun Wu Deeptha Kumaraswamy Natalie Burchat Hong Ye Yongjia Gong Liping Zhao Yan Y. Lam Harini Sampath 《Nutrients》2021,13(2)
7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies. 相似文献
8.
Rabea Asleh Hilmi Alnsasra Amir Lerman Alexandros Briasoulis Naveen L. Pereira Brooks S. Edwards Takumi Toya John M. Stulak Alfredo L. Clavell Richard C. Daly Sudhir S. Kushwaha 《American journal of transplantation》2021,21(2):626-635
We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk. 相似文献
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10.
Sangeeta Shah Poonam Lavaju Priyanka Bharati Icchya Joshi 《Orbit (Amsterdam, Netherlands)》2017,36(1):55-57
Ocular involvement of rhinosporidiosis is seen in about 15% of cases and clinically appears as a freely mobile, granular, pink, fleshy sessile or pedunculated mass. The conjunctiva is the most common site of origin. A 25-year-old male presented with a painless mass in the lower part of the left eye for 6 months which was gradually progressive. Examination revealed a pedunculated mass of 15 mm x 15 mm arising from the lower palpebrae of the left eye retracting the lower lid. It appeared to be vascular with few white spots at the apex. Rest of the ocular examinations was within the normal limit. The presentations of ocular rhinosporidiosis vary. Though the conjunctival origin is very common, it may not have a classic pink fleshy appearance at all times. A vascular/cystic painless conjunctival mass should also be considered as a case of rhinosporidiosis in prone areas. 相似文献