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.
Topics: Population, Pregnancy, Antiphospholipid syndrome, Medicine, Cancer
Papers published on a yearly basis
Papers
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TL;DR: Data show that B16/HSVtk+ cells die predominantly by necrosis, rather than apoptosis, on exposure to GC, a process which may be associated with the generation of anti‐tumour inflammatory responses, and discuss the development of improved vectors for gene therapy to augment these effects in vivo.
Abstract: Direct delivery of the herpes simplex virus thymidine kinase (HSVtk) gene, in combination with the prodrug ganciclovir (GC), has been used for the treatment of localised, inoperable tumours. Several groups have shown that when rodent tumours are ablated in vivo with suicide genes, anti-tumour immunity can also be generated. Hence, this approach may also be useful in treating disseminated disease. Here we have studied the mechanisms associated with this anti-tumour immunity. In B16 HSVtk+ tumours being killed in vivo with GC treatment, we observed the induction of a pronounced intratumoural infiltrate of macrophages, CD4+ and CD8+ T cells. In addition, using reverse transcriptase polymerase chain reaction, expression of interleukin (IL)-2, IL-12, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and granulocyte/macrophage colony-stimulating factor (GM-CSF) but not IL-4, IL-6 or IL-10, was observed, a profile of cytokine expression which resembles that of a Th1 immune response. To complement these findings, we also investigated the mechanisms by which expression of HSVtk leads to cell death. Our data show that B16/HSVtk+ cells die predominantly by necrosis, rather than apoptosis, on exposure to GC, a process which may be associated with the generation of anti-tumour inflammatory responses. From these data we propose a model for the induction of anti-tumour immunity using suicide genes and discuss the development of improved vectors for gene therapy to augment these effects in vivo.
196 citations
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TL;DR: This study implies a stronger relationship between these disorders than a previously published figure of 7-12% and is clinically significant as RBD is a potentially distressing but readily treatable disorder.
196 citations
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TL;DR: This review addresses the increasingly prolific literature from studies in man and animals suggesting that maternal obesity, a diet rich in calories or excess gestational weight gain may, through perturbation of the intrauterine environment, lead to lifelong risk of obesity and related disorders in the child.
195 citations
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TL;DR: It is concluded that, while there is substantial evidence that irritant receptors in the laryngeal wall and RARs in the tracheobronchial mucosa can cause cough, the evidence for such a similar direct role for C-fibre receptors is tenuous.
195 citations
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Radboud University Nijmegen Medical Centre1, McGill University2, St James's University Hospital3, St Thomas' Hospital4, Technische Universität München5, University of Mainz6, University of Cambridge7, King Edward Medical University8, University Medical Center Utrecht9, Johns Hopkins University10, University College London11
TL;DR: The LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease and the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA is emphasized.
Abstract: Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.
195 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 |