Institution
St Thomas' Hospital
Healthcare•London, United Kingdom•
About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: It is provided the first evidence that PKCα or a PKC α‐associated serine/threonine kinase can phosphorylate the ERM C‐terminal threonine residue within a kinase–ezrin molecular complex in vivo.
Abstract: Protein kinase C (PKC) α has been implicated in β1 integrin-mediated cell migration. Stable expression of PKCα is shown here to enhance wound closure. This PKC-driven migratory response directly correlates with increased C-terminal threonine phosphorylation of ezrin/moesin/radixin (ERM) at the wound edge. Both the wound migratory response and ERM phosphorylation are dependent upon the catalytic function of PKC and are susceptible to inhibition by phosphatidylinositol 3-kinase blockade. Upon phorbol 12,13-dibutyrate stimulation, green fluorescent protein–PKCα and β1 integrins co-sediment with ERM proteins in low-density sucrose gradient fractions that are enriched in transferrin receptors. Using fluorescence lifetime imaging microscopy, PKCα is shown to form a molecular complex with ezrin, and the PKC-co-precipitated endogenous ERM is hyperphosphorylated at the C-terminal threonine residue, i.e. activated. Electron microscopy showed an enrichment of both proteins in plasma membrane protrusions. Finally, overexpression of the C-terminal threonine phosphorylation site mutant of ezrin has a dominant inhibitory effect on PKCα-induced cell migration. We provide the first evidence that PKCα or a PKCα-associated serine/threonine kinase can phosphorylate the ERM C-terminal threonine residue within a kinase–ezrin molecular complex in vivo.
306 citations
••
TL;DR: Although some lipid-modifying treatments have been shown to increase HCY levels, there is no evidence that this attenuates or compromises the beneficial effects of such treatments on cardiovascular risk, and therefore data suggest that HCY is a marker, rather than a cause, of CVD.
Abstract: Elevated homocysteine (HCY) levels can be caused by a number of factors, including folate and B-vitamin deficiency, pre-existing atherosclerotic disease, diabetes and various drugs. Epidemiological evidence, as well as data from retrospective and prospective studies, supports an association between elevated HCY levels and increased risk of cardiovascular disease (CVD). However, whether lowering HCY levels by administration of folate and vitamins B6 and B12 is associated with any significant decrease in vascular risk remains the subject of ongoing debate. Although the major studies that have reported to date show that vitamin supplementation was associated with a decrease in HCY levels, this failed to have any significant effect on cardiovascular risk. Furthermore, although some lipid-modifying treatments have been shown to increase HCY levels, there is no evidence that this attenuates or compromises the beneficial effects of such treatments on cardiovascular risk. Taken together, these data suggest that HCY is a marker, rather than a cause, of CVD and therefore do not provide support for routine screening for and treatment of elevated HCY to prevent CVD. Data from ongoing clinical trials are awaited to clarify this issue.
304 citations
••
TL;DR: Dietary silicon correlated positively and significantly with BMD at all hip sites in men and premenopausal women, but not in postmenopausalWomen, suggesting that increased silicon intake is associated with increased cortical BMD in these populations.
Abstract: The role of dietary silicon in bone health in humans is not known. In a cross-sectional, population-based study (2847 participants), associations between dietary silicon intake and BMD were investigated. Dietary silicon correlated positively and significantly with BMD at all hip sites in men and premenopausal women, but not in postmenopausal women, suggesting that increased silicon intake is associated with increased cortical BMD in these populations.
Introduction: Osteoporosis is a burgeoning health and economic issue. Agents that promote bone formation are widely sought. Animal and cellular data suggest that the orthosilicate anion (i.e., dietary silicon) is involved in bone formation. The intake of silicon (Si, ∼30 mg/day) is among the highest for trace elements in humans, but its contribution to bone health is not known.
Materials and Methods: In a cross-sectional, population-based study, we examined the association between silicon intake and bone mineral density (BMD) in 1251 men and 1596 pre- and postmenopausal women in the Framingham Offspring cohort (age, 30–87 years) at four hip sites and lumbar spine, adjusting for all potential confounding factors known to influence BMD and nutrient intake.
Results: Silicon intake correlated positively with adjusted BMD at four hip sites in men and premenopausal women, but not in postmenopausal women. No significant association was observed at the lumbar spine in any group. Categorical analysis by Si intake, or energy-adjusted Si intake, supported these findings, and showed large differences in BMD (up to 10%) between the highest (>40 mg Si/day) and lowest (<14 mg Si/day) quintiles of silicon intake. A significant association at the lumbar spine in men was also observed. Further analyses indicated that some of the effects seen for moderate consumption of alcoholic beverages on BMD might be attributed to Si intake.
Conclusions: These findings suggest that higher dietary silicon intake in men and younger women may have salutary effects on skeletal health, especially cortical bone health, that has not been previously recognized. Confirmation of these results is being sought in a longitudinal study and by assessment of the influence of silicon intake on bone markers in this cohort.
304 citations
••
TL;DR: Pre/post comparison in elective orthopaedic patients showed improved (within methodological limitations) post-operative outcomes indicative of better clinical effectiveness and efficiency, and contributed to the service obtaining mainstream funding.
Abstract: Background: older people undergoing elective surgery have significant post-operative problems prolonging hospitalisation. Objective: to design, embed, and evaluate an evidence-based comprehensive geriatric assessment (CGA) service for at-risk older patients undergoing elective surgery. Setting: urban teaching hospital. Subjects: elective surgical patients aged 65+. Intervention: multidisciplinary preoperative CGA service with post-operative follow-through (proactive care of older people undergoing surgery ['POPS']). Methods: observational cohort study and multilevel surveys (development and modelling phase). Prospective 'before and after' comparison (exploratory evaluation). Results: findings from the development phase showed high levels of preoperative co-morbidity, no multidisciplinary preoperative input, and multiple potentially preventable post-operative problems delaying discharge in older elective surgery patients. Comparison of 2 cohorts of elective orthopaedic patients (pre-POPS vs POPS, N = 54) showed the POPS group had fewer post-operative medical complications including pneumonia (20% vs 4% \p = 0.008]) and delirium (19% vs 6% \p = 0.036]), and significant improvements in areas reflecting multidisciplinary practice including pressure sores (19% vs 4% \p = 0.028]), poor pain control (30% vs 2% [p<0.001]), delayed mobilisation (28% vs 9% \p = 0.012]) and inappropriate catheter use (20% vs 7% \p = 0.046]). Length of stay was reduced by 4.5 days. There were fewer delayed discharges relating to medical complications (37% vs 13%) or waits for OT assessment or equipment (20% vs 4%). Conclusion: a proactive evidence-based CGA service for at-risk older elective surgical patients was developed according to MRC framework for complex interventions. Pre/post comparison in elective orthopaedic patients showed improved (within methodological limitations) post-operative outcomes indicative of better clinical effectiveness and efficiency, and contributed to the service obtaining mainstream funding. Informed by the present study, a randomised controlled trial is ongoing.
302 citations
••
302 citations
Authors
Showing all 12132 results
Name | H-index | Papers | Citations |
---|---|---|---|
David J. Hunter | 213 | 1836 | 207050 |
Rory Collins | 162 | 489 | 193407 |
Steven Williams | 144 | 1375 | 86712 |
Geoffrey Burnstock | 141 | 1488 | 99525 |
Nick C. Fox | 139 | 748 | 93036 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |
David A. Jackson | 136 | 1095 | 68352 |
Paul Harrison | 133 | 1400 | 80539 |
Roberto Ferrari | 133 | 1654 | 103824 |
David Taylor | 131 | 2469 | 93220 |
Keith Hawton | 125 | 657 | 55138 |
Nicole Soranzo | 124 | 316 | 74494 |
Roger Williams | 122 | 1455 | 72416 |
John C. Chambers | 122 | 645 | 71028 |
Derek M. Yellon | 122 | 638 | 54319 |