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91.
Chris Kypridemos Piotr Bandosz Graeme L. Hickey Maria Guzman-Castillo Kirk Allen Iain Buchan Simon Capewell Martin O’Flaherty 《PloS one》2015,10(4)
Background
Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups.Methods and Findings
This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual ‘no statins’ scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our ‘no statins’ scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men.Conclusions
Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants. 相似文献92.
Ali NA Gaughan AA Orosz CG Baran CP McMaken S Wang Y Eubank TD Hunter M Lichtenberger FJ Flavahan NA Lawler J Marsh CB 《PloS one》2008,3(4):e1914
Latency Associated Peptide (LAP) binds TGF-beta1, forming a latent complex. Currently, LAP is presumed to function only as a sequestering agent for active TGF-beta1. Previous work shows that LAP can induce epithelial cell migration, but effects on leukocytes have not been reported. Because of the multiplicity of immunologic processes in which TGF-beta1 plays a role, we hypothesized that LAP could function independently to modulate immune responses. In separate experiments we found that LAP promoted chemotaxis of human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-beta1 activity. Further studies revealed that disruption of specific LAP-thrombospondin-1 (TSP-1) interactions prevented LAP-induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation. 相似文献
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96.
Andrew?A. Davis Matthew?J. Farrar Nozomi Nishimura Moonsoo?M. Jin Chris?B. Schaffer 《Biophysical journal》2013,105(4):862-871
Femtosecond laser optoporation is a powerful technique to introduce membrane-impermeable molecules, such as DNA plasmids, into targeted cells in culture, yet only a narrow range of laser regimes have been explored. In addition, the dynamics of the laser-produced membrane pores and the effect of pore behavior on cell viability and transfection efficiency remain poorly elucidated. We studied optoporation in cultured cells using tightly focused femtosecond laser pulses in two irradiation regimes: millions of low-energy pulses and two higher-energy pulses. We quantified the pore radius and resealing time as a function of incident laser energy and determined cell viability and transfection efficiency for both irradiation regimes. These data showed that pore size was the governing factor in cell viability, independently of the laser irradiation regime. For viable cells, larger pores resealed more quickly than smaller pores, ruling out a passive resealing mechanism. Based on the pore size and resealing time, we predict that few DNA plasmids enter the cell via diffusion, suggesting an alternative mechanism for cell transfection. Indeed, we observed fluorescently labeled DNA plasmid adhering to the irradiated patch of the cell membrane, suggesting that plasmids may enter the cell by adhering to the membrane and then being translocated. 相似文献
97.
Gert Rijksen Gerard E. J. Staal Margreet J. M. van der Vlist Frits A. Beemer Jaap Troost Wolf Gutensohn Jan P. R. M. van Laarhoven Chris H. M. M. de Bruyn 《Human genetics》1981,57(1):39-47
Summary A patient with the full clinical expression of the classical Lesch-Nyhan syndrome is presented with a residual hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity of 5–10% in erythrocyte lysate and about 30% in fibroblast lysate. The activities of other erythrocyte enzymes of purine metabolism were typical for a classical Lesch-Nyhan patient. The effects of allopurinol therapy on the excretion of urinary purine metabolites were studied by a newly developed isotachophoretic technique.The unusually high residual activity of HGPRT in erythrodytes and fibroblasts of the patient enabled the enzymologic characterization of the mutant enzyme: in fibroblasts the affinities for the substrates hypoxanthine and guanine were normal. However, there was an increased apparent K
m for phosphoribosylpyrophosphate (PRPP), a complete absence of product inhibition by IMP and GMP, and a decreased heat stability. Addition of PRPP did not stabilize the mutant enzyme. In addition to the altered properties of the fibroblast enzyme, the K
m of the erythrocyte enzyme for hypoxanthine was also increased.Immunoprecipitation experiments revealed the presence of an approximately normal amount of material cross-reacting with anti-human HGPRT antiserum. However, it appeared that this cross-reacting material had a decreased stability. When intact erythrocytes were incubated with radiolabeled purine bases, no formation of IMP or GMP could be detected, despite the relatively high residual activity of HGPRT in the hemolysate. The results fit the following hypothesis: as a consequence of a structural mutation affecting the PRPP-site of the enzyme and a decreased heat stability, the activity of the mutant enzyme under in vivo conditions is virtually zero.In the erythrocytes of the patient's mother a normal HGPRT-activity was found. However, the activity in her fibroblasts was lower than normal, while a decreased heat stability and an intermediate behavior towards IMP could be shown.Hair root analysis of several members of the patient's family confirmed the heterozygosity of the mother, whereas no other heterozygotes could be detected. The family anamnesis did not show other cases of Lesch-Nyhan syndrome. These findings were taken as evidence that the patient described in this paper might represent a mutation orginating from the gametes in either of the maternal grandparents. 相似文献
98.
Kuczenski Brandon Mutel Chris Srocka Michael Scanlon Kelly Ingwersen Wesley 《The International Journal of Life Cycle Assessment》2021,26(3):483-496
The International Journal of Life Cycle Assessment - The flexibility of life cycle inventory (LCI) background data selection is increasing with the increasing availability of data, but this comes... 相似文献
99.
Itten René Hischier Roland Andrae Anders S. G. Bieser Jan C. T. Cabernard Livia Falke Annemarie Ferreboeuf Hugues Hilty Lorenz M. Keller Regula L. Lees-Perasso Etienne Preist Chris Stucki Matthias 《The International Journal of Life Cycle Assessment》2020,25(10):2093-2098
The International Journal of Life Cycle Assessment - 相似文献
100.
Y Zhao H Zacur C Cheadle N Ning J Fan NF Vlahos 《Reproductive biology and endocrinology : RB&E》2012,10(1):72-12
ABSTRACT: BACKGROUND: Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles. METHODS: The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3-5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P+E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel. RESULTS: A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p<0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P+E support respectively, 3-5 days after retrieval. During the peri-implantation period (3-5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P+E group respectively as compared to the no steroid supplementation group. CONCLUSION: Luteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P+E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes. 相似文献