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
Papers
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TL;DR: The data suggest that int-1 and int-2 may act cooperatively in the genesis of mammary carcinomas, and because in five cases activation occurred in the apparent absence of an adjacent provirus, it is clear that other loci and mechanisms contribute to tumorigenesis.
Abstract: Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus
125 citations
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TL;DR: It is predicted that this mutant GHR protein would not be anchored in the cell membrane and would be measurable in the circulation as GHBP, hence explaining the phenotype of severe GH resistance combined with elevated circulating GHBP.
Abstract: Laron syndrome (LS) is a severe autosomal recessive form of GH resistance resulting from molecular defects in the GH receptor (GHR). Affected individuals have extreme short stature and a typical facial phenotype. The point mutations in the GHR gene identified in this condition have until now been confined to the region encoding the extracellular domain of the receptor. We report here the first homozygous point mutation within the intracellular domain of the GHR in two LS cousins distinguishable from classical LS patients only by the presence of elevated GH-binding protein (GHBP) in their serum. A G to C transversion at the vital - 1 position in the splice donor site of exon 8 disrupts normal splicing, resulting in the complete skipping of exon 8, producing a mutant GHR protein lacking transmembrane and intracellular domains. We predict that this mutant protein would not be anchored in the cell membrane and would be measurable in the circulation as GHBP, hence explaining the phenotype of severe GH resistan...
125 citations
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TL;DR: There is an urgent need for an intervention which could be used in rural hospitals, thus preventing the hazardous and expensive emergency transfer of patients to the capital.
Abstract: Deliberate self-harm is an important problem in the developing world. Ingestion of yellow oleander seeds (Thevetia peruviana) has recently become a popular method of self-harm in northern Sri Lanka -- there are now thousands of cases each year. These seeds contain cardiac glycosides that cause vomiting, dizziness, and cardiac dysrhythmias such as conduction block affecting the sinus and AV nodes. This paper reports a study of the condition's mortality and morbidity conducted in 1995 in Anuradhapura General Hospital, a secondary referral centre serving 750 000 people in Sri Lanka's north central province. 415 cases were admitted to the hospital during 11 months; 61% were women and 46% were less than 21 years old. A prospective study of 79 patients showed that 6% died soon after admission. 43% presented with marked cardiac dysrhythmias which necessitated ther transfer to the coronary care unit in Colombo for prophylactic temporary cardiac pacing. The reasons for the acts of self-harm were often relatively trivial, particularly in children; most denied that they wished to die. Unfortunately, the case fatality rate for oleander poisoning in Sri Lanka is at least 10%. This epidemic is not only causing many unnecessary deaths, it is also putting immense stress on the already stretched Sri Lankan health services. There is an urgent need for an intervention which could be used in rural hospitals, thus preventing the hazardous and expensive emergency transfer of patients to the capital.
125 citations
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TL;DR: The present investigation indicates that inflammatory macrophages that have entered them mitotic cycle fall into one of three categories; cells newly arrived from the circulation, cells form a high turn over pool heavily dependent on recruitment from the bone marrow , and cells forming a self-sufficient population largely independent of marrow recruitment.
Abstract: It has previously been shown that macrophages in various types of inflamed tissue proliferate, whereas macrophages on subcutaneously inserted glass cover slips showed little such activity. This discrepancy suggested that macrophage proliferation in inflammation might be a complex and variable process. The present investigation indicates that inflammatory macrophages that have entered the mitotic cycle fall into one of three categories; cells newly arrived from the circulation, cells forming a high turnover pool heavily dependent on recruitment from the bone marrow, and cells forming a self-sufficient population largely independent of marrow recruitment. In reactions provoked by subcutaneous insertion of cover slips, uptake of a pulse of [$^{3}$H]T by perivascular but haematogenous macrophages begins at 4 h but is not evident in macrophages adhering to the cover slip until 2 to 4 days. Contrary to previous belief, DNA synthesis in multinucleate giant cells does occur but not until the cells are about 14 days old. DNA synthesis is frequently synchronous in the nuclei of a given cell. The percentage of connective tissue and cover-slip macrophages undergoing DNA synthesis becomes equal at 4 to 6 days. Selective X-irradiation of the bone marrow or the reaction site showed that the cells remain in the tissues or on the cover slip for only one or two days and that the lesion is totally dependent on daily recruitment from the marrow. Turnover is highest in the first few days of the lesion. The newly arrived macrophages that monopolize these early lesions have the curious property of resisting removal from the granuloma by dissection, whereas established arrivals are teased out with ease. The presence or absence of DNA synthesis in viable macrophages is determined partly by factors within the cell and partly by its environment. This was shown by transferring coverslip macrophages from early lesions to more mature reactions and vice versa and to tissue culture. Early macrophages unable to enter the mitotic cycle retained this disability under all circumstances. Macrophages from older reactions that normally synthesize DNA continued to do so in tissue culture but ceased this activity on transfer to early inflammatory lesions, indicating the inhibitory effect of this particular environment. Peritoneal macrophages that synthesize DNA very poorly in the normal peritoneum and in tissue culture entered the mitotic cycle in large numbers when transferred to inflammatory reactions old enough to have ceased to inhibit DNA synthesis. Similarly, blood monocytes that show even less proliferation than peritoneal cells in vitro, exhibited intense DNA synthesis 2 days after implantation into inflamed subcutaneous tissue. Since small numbers of monocytes gave rise, within a few days, to large numbers of macrophages, an association was established between incorporation of [$^{3}$H]T into nuclear DNA and net increase in cell numbers. The technique of selective X-irradiation and dissection were applied to various types of dermal and subcutaneous inflammation. In reactions to bovine fibrinogen all DNA-synthesizing macrophages were found to be of the newly arrived type. More unexpectedly in even long-established reactions to B. pertussis vaccine, almost all the macrophages were again of this type, presumably because of the toxicity of the killed organisms. Granulomata due to incomplete Freund adjuvant were similar to the reactions provoked by subcutaneous cover slips in that once the lesion was established most of the macrophages belonged to a high-turnover pool continuously replenished by fresh recruits from the marrow. Carrageenan granulomata revealed the existence of a third type of macrophage population, largely independent of further marrow recruitment. Presumably the low toxicity of carrageenan permits the expression of macrophage longevity which augmented by occasional mitotic activity maintains a self-sufficient population.
125 citations
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TL;DR: The results suggest that, with maturity, progressive cell degeneration primarily by apoptosis results in clearance of certain cellular populations resulting in the typical keloid lesion, however, the persistence of fibroblast proliferation at the dermal/keloid interface propagates the fibrosis.
Abstract: Keloids are collagenous lesions acquired as a result of abnormal wound heating. In this study we have assessed the potential role of proliferation, apoptosis, and necrosis in keloids. Samples were immunolabeled for proliferating cell nuclear antigen or DNA strand breaks or stained with acridine orange. Proliferating cells were observed in the basal layer of the epidermis and fibroblasts in the dermis, the numbers of the latter being increased in comparison with normal skin. No proliferating cells were observed in the central region of the keloid. In normal skin, apoptotic cells were restricted to the basal layer of the epidermis. In keloid samples, numerous apoptotic cells were observed in the epidermis and dermis; the number and distribution of positive cells decreased more distal to the keloid lesion. Apoptotic endothelial cells of a small proportion of blood vessels in the dermis were also observed. Evidence of necrosis was also seen in the dermis. These results suggest that, with maturity, progressive cell degeneration primarily by apoptosis results in clearance of certain cellular populations resulting in the typical keloid lesion. However, the persistence of fibroblast proliferation at the dermal/keloid interface propagates the fibrosis.
125 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 |