Institution
St Bartholomew's Hospital
Healthcare•London, United Kingdom•
About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.
Topics: Population, Cancer, Transplantation, Diabetes mellitus, Pregnancy
Papers published on a yearly basis
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TL;DR: It is suggested that this degree of TNF alpha production probably contributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endothelial membranes, increasing inflammatory cell recruitment, and by prothrombotic effects on the vascular endothelium.
Abstract: This study determined the location and tissue density of cells immunoreactive for tumour necrosis factor alpha (TNF alpha) in intestinal specimens from 24 patients with chronic inflammatory bowel disease (15 with Crohn's disease, nine with ulcerative colitis) and 11 controls. There was significantly increased density of TNF alpha immunoreactive cells in the lamina propria of both ulcerative colitis and Crohn's disease specimens, although the distribution of these cells differed in the two conditions. In ulcerative colitis most of the TNF alpha immunoreactivity was seen in the subepithelial macrophages, with comparatively less in the deep lamina propria, while in Crohn's disease immunoreactive cells were distributed evenly throughout the lamina propria. Increased submucosal immunoreactivity was found only in Crohn's disease, in which TNF alpha positive macrophages tended to cluster around arterioles and venules, often infiltrating and disrupting vascular endothelium. It is suggested that this degree of TNF alpha production probably contributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endothelial membranes, increasing inflammatory cell recruitment, and by prothrombotic effects on the vascular endothelium.
529 citations
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University of Leicester1, National Institute for Health Research2, University of Oxford3, Wellcome Trust Centre for Human Genetics4, University of Cambridge5, Queen Mary University of London6, Technische Universität München7, Stanford University8, Icahn School of Medicine at Mount Sinai9, London North West Healthcare NHS Trust10, Imperial College London11, Imperial College Healthcare12, University of Dundee13, University of Leeds14, Massachusetts Institute of Technology15, Tartu University Hospital16, University of Ioannina17, Umeå University18, Harvard University19, Lund University20, Peking Union Medical College21, University College London22, University of Tampere23, Vanderbilt University24, Heidelberg University25, Medical University of Graz26, Synlab Group27, University of Ottawa28, University of Tartu29, Lebanese American University30, King Abdulaziz University31, University of Manchester32, Central Manchester University Hospitals NHS Foundation Trust33, National Institutes of Health34, St Bartholomew's Hospital35, Manchester Academic Health Science Centre36, Wellcome Trust Sanger Institute37, University of Lübeck38, Harokopio University39, Karolinska University Hospital40
TL;DR: This approach identified 13 new loci at genome-wide significance, 12 of which were on the previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals.
Abstract: Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
529 citations
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TL;DR: The problems associated with this exercise were viewed from a historical perspective and survival analysis of 447 patients receiving surgery for rectal adenocarcinoma was undertaken.
Abstract: The grade of a tumour is gauged on the subjective assessment of a number of histopathological parameters. The problems associated with this exercise were viewed from a historical perspective and survival analysis of 447 patients receiving surgery for rectal adenocarcinoma was undertaken. Only deaths from rectal adenocarcinoma were included as events in the survival analysis. Seven grade-related parameters were scored by one observer. A grading system was constructed using the Cox regression model. The variables in the best-fitting parsimonious model comprised lymphocytic infiltration, tubule configuration and pattern of growth. Scores were derived from the model and a four grade system was created in which the groups were of similar size. Good reproducibility of the selected histopathological parameters was demonstrated. Grade-related parameters were then allowed to compete with stage-related parameters in an overall model of pathological prognostic categories. The parameters selected in the best model were number of affected lymph nodes, the presence of lymphocytic infiltration and extent of spread through bowel wall. A set of five prognostic categories was developed from this model.
526 citations
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University of Leicester1, University of Cambridge2, National Institute for Health Research3, Baker IDI Heart and Diabetes Institute4, Manchester Academic Health Science Centre5, Imperial College London6, St Bartholomew's Hospital7, Icahn School of Medicine at Mount Sinai8, Wellcome Trust Centre for Human Genetics9, Queen Mary University of London10
TL;DR: The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.
522 citations
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TL;DR: The results suggest that TNF‐α is an important mediator of inflammation in the human gut, and, furthermore, may play a role in the growth failure frequently seen in children with inflammatory bowel disease.
Abstract: The spot-ELISA technique has been used to enumerate the frequency of cells secreting tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), isolated from biopsies of normal intestine and from biopsies of children with inflammatory bowel disease. TNF-alpha production was undetectable in six out of 12 biopsies from normal intestine and in the other six biopsies it ranged from 60 to 580 TNF-alpha-secreting cells/10(6) isolated intestinal cells. In contrast, cells isolated from biopsies of children with Crohn's disease (n = 9) all showed elevated frequencies of TNF-alpha-secreting cells (500-12,000 secreting cells/10(6) cells). In ulcerative colitis, four out of eight children had increased production of TNF-alpha and in children with indeterminate colitis two out of three had elevated levels. There was no correlation between plasma TNF-alpha levels and the number of intestinal cells secreting TNF-alpha. In controls and all groups of patients IFN-gamma-secreting cells were uncommon. These results suggest that TNF-alpha is an important mediator of inflammation in the human gut, and, furthermore, may play a role in the growth failure frequently seen in children with inflammatory bowel disease.
510 citations
Authors
Showing all 11065 results
Name | H-index | Papers | Citations |
---|---|---|---|
Philippe Froguel | 166 | 820 | 118816 |
Geoffrey Burnstock | 141 | 1488 | 99525 |
Michael A. Kamm | 124 | 637 | 53606 |
David Scott | 124 | 1561 | 82554 |
Csaba Szabó | 123 | 958 | 61791 |
Roger Williams | 122 | 1455 | 72416 |
Derek M. Yellon | 122 | 638 | 54319 |
Walter F. Bodmer | 121 | 579 | 68679 |
John E. Deanfield | 120 | 497 | 61067 |
Paul Bebbington | 119 | 583 | 46341 |
William C. Sessa | 117 | 383 | 52208 |
Timothy G. Dinan | 116 | 689 | 60561 |
Bruce A.J. Ponder | 116 | 403 | 54796 |
Alexandra J. Lansky | 114 | 632 | 54445 |
Glyn Lewis | 113 | 734 | 49316 |