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Institution

John Radcliffe Hospital

HealthcareOxford, Oxfordshire, United Kingdom
About: John Radcliffe Hospital is a healthcare organization based out in Oxford, Oxfordshire, United Kingdom. It is known for research contribution in the topics: Population & Antigen. The organization has 14491 authors who have published 23670 publications receiving 1459015 citations.


Papers
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Journal ArticleDOI
TL;DR: The extent of fibrinogen depletion during trauma hemorrhage, the response to replacement therapy and association with patient outcomes remain unclear remain unclear.

462 citations

Journal ArticleDOI
TL;DR: It is reported here that XRCC1, another essential protein involved in the maintenance of genome stability, physically interacts with APE1 and stimulates its enzymatic activities, extending the coordinating role of XR CC1 to the initial step of the repair of DNA abasic sites.
Abstract: The major human AP endonuclease APE1 (HAP1, APEX, Ref1) initiates the repair of abasic sites generated either spontaneously, from attack of bases by free radicals, or during the course of the repair of damaged bases. APE1 therefore plays a central role in the base excision repair (BER) pathway. We report here that XRCC1, another essential protein involved in the maintenance of genome stability, physically interacts with APE1 and stimulates its enzymatic activities. A truncated form of APE1, lacking the first 35 amino acids, although catalytically proficient, loses the affinity for XRCC1 and is not stimulated by XRCC1. Chinese ovary cell lines mutated in XRCC1 have a diminished capacity to initiate the repair of AP sites. This defect is compensated by the expression of XRCC1. XRCC1, acting as both a scaffold and a modulator of the different activities involved in BER, would provide a physical link between the incision and sealing steps of the AP site repair process. The interaction described extends the coordinating role of XRCC1 to the initial step of the repair of DNA abasic sites.

461 citations

Journal ArticleDOI
TL;DR: Fifty sequences from the mouse genome database containing simple sequence repeats or microsatellites have been analysed for size variation using the polymerase chain reaction and gel electrophoresis to facilitate construction of high resolution maps of both the mouse and human genomes.
Abstract: Fifty sequences from the mouse genome database containing simple sequence repeats or microsatellites have been analysed for size variation using the polymerase chain reaction and gel electrophoresis. 88% of the sequences, most of which contain the dinucleotide repeat, CA/GT, showed size variations between different inbred strains of mice and the wild mouse, Mus spretus. 62% of sequences had 3 or more alleles. GA/CT and AT/TA-containing sequences were also variable. About half of these size variants were detectable by agarose gel electrophoresis. This simple approach is extremely useful in linkage and genome mapping studies and will facilitate construction of high resolution maps of both the mouse and human genomes.

460 citations

Journal ArticleDOI
TL;DR: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year after randomization.
Abstract: Background The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninfer...

460 citations

Journal ArticleDOI
TL;DR: It is suggested that aggressive tumours rapidly outgrow their vascular supply in certain areas, leading to areas of prolonged hypoxia within the tumour and, subsequently, to necrosis.
Abstract: Necrosis is a common feature of invasive carcinoma of the breast and is caused by chronic ischaemia leading to infarction Although necrosis was previously assumed to be due to a generally poor blood supply in the tumour, in this study we show that it is present in tumours with focal areas of high vascular density situated away from the actual sites of necrosis This may account, in part, for the previous observation that necrosis is linked to poor prognosis in this disease Highly angiogenic tumours often display blood vessel shunting from one tumour area to another, which further exacerbates ischaemia and the formation of tumour necrosis We have recently demonstrated that high focal microphage infiltration into breast tumours is significantly associated with increased tumour angiogenesis and poor prognosis and that the macrophages accumulate in poorly vascularized, hypoxic areas within breast tumours In order to investigate the interactions of macrophages with chronic ischaemia (as reflected by the presence of necrosis) and angiogenesis in breast tumours, we quantified the levels of these three biological parameters in a series of 109 consecutive invasive breast carcinomas We found that the degree of tumour necrosis was correlated with both microphage infiltration (Mann-Whitney U, P-value = 00009; chi-square, P-value = 001) and angiogenesis (Mann-Whitney U P-value = 00008, chi square P-value = 003) It was also observed that necrosis was a feature of tumours possessing an aggressive phenotype, ie high tumour grade (chi-square, P-value < 0001), larger size (Mann-Whitney U, P-value = 0003) and low oestrogen receptor status (Mann-Whitney U, P-value = 0008; chi-square, P-value < 0008) We suggest, therefore, that aggressive tumours rapidly outgrow their vascular supply in certain areas, leading to areas of prolonged hypoxia within the tumour and, subsequently, to necrosis This, in turn, may attract macrophages into the tumour, which then contribute to the angiogenic process, giving rise to an association between high levels of angiogenesis and extensive necrosis

459 citations


Authors

Showing all 14542 results

NameH-indexPapersCitations
Douglas G. Altman2531001680344
Salim Yusuf2311439252912
David J. Hunter2131836207050
Mark I. McCarthy2001028187898
Stuart H. Orkin186715112182
Richard Peto183683231434
Ralph M. Steinman171453121518
Adrian L. Harris1701084120365
Rory Collins162489193407
Nicholas J. White1611352104539
David W. Johnson1602714140778
David Cella1561258106402
Edmund T. Rolls15361277928
Martin A. Nowak14859194394
Kypros H. Nicolaides147130287091
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202311
202252
20211,048
20201,013
2019916
2018773