John Radcliffe Hospital

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.

ERIC sequences: a novel family of repetitive elements in the genomes of Escherichia coli, Salmonella typhimurium and other enterobacteria

Abstract: We describe a family of highly conserved, Enterobacterial Repetitive Intergenic Consensus (ERIC) sequences, 14 of which have been identified in Escherichia coli and Salmonella typhimurium and a further three in other enterobacterial species (Yersinia pseudotuberculosis, Klebsiella pneumoniae and Vibrio cholerae). ERIC sequences are 126 bp long and appear to be restricted to transcribed regions of the genome, either in intergenic regions of polycistronic operons or in untranslated regions upstream or downstream of open reading frames. ERIC sequences are highly conserved at the nucleotide sequence level but their chromosomal locations differ between species. Several features of ERIC sequences resemble those of REP sequences (Stern et al., 1984) although the nucleotide sequence is entirely different. The question of whether ERICs have a specific function, or represent a form of 'selfish' DNA, is discussed.

Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection.

Abstract: It has been a long-standing dogma that host sensitization against fully- vascularized organ allografts occurs peripherally within the graft itself. In this report we show that donor-derived MHC class II-positive (Ia+) DL migrate rapidly out of mouse cardiac allografts into the recipients' spleens where they home to the peripheral white pulp and associate predominantly with CD4+ T lymphocytes. This provides a novel route for central sensitization against fully vascularized allografts, and most likely represents a pathway by which immune responses are generated against antigens on blood-borne DL emigrating from peripheral tissues.

Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation.

Abstract: Objective To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment. Data sources The Cochrane Central Register of Clinical Trials, Medline, Embase, CINAHL, the National Research Register, the NHS Trusts Clinical Trials Register, the Medical Research Council UK database, the NHS Research and Development Health Technology Assessment Programme, the British Heart Foundation database, citation review of relevant primary and review articles, and expert informants. Study selection Randomised and quasi-randomised controlled studies that compared early tracheostomy with either late tracheostomy or prolonged endotracheal intubation. From 15 950 articles screened, 12 were identified as “randomised or quasi-randomised” controlled trials, and five were included for data extraction. Data extraction Five studies with 406 participants were analysed. Descriptive and outcome data were extracted. The main outcome measure was mortality in hospital. The incidence of hospital acquired pneumonia, length of stay in a critical care unit, and duration of artificial ventilation were also recorded. Random effects meta-analyses were performed. Results Early tracheostomy did not significantly alter mortality (relative risk 0.79, 95% confidence interval 0.45 to 1.39). The risk of pneumonia was also unaltered by the timing of tracheostomy (0.90, 0.66 to 1.21). Early tracheostomy significantly reduced duration of artificial ventilation (weighted mean difference –8.5 days, 95% confidence interval –15.3 to –1.7) and length of stay in intensive care (–15.3 days, –24.6 to –6.1). Conclusions In critically ill adult patients who require prolonged mechanical ventilation, performing a tracheostomy at an earlier stage than is currently practised may shorten the duration of artificial ventilation and length of stay in intensive care.

Replication stress induces sister-chromatid bridging at fragile site loci in mitosis

Abstract: Several inherited syndromes in humans are associated with cancer predisposition The gene products defective in two of these disorders, BLM (a helicase defective in Bloom's syndrome) and FANC A-N (defective in Fanconi anaemia), associate in a multienzyme complex called BRAFT How these proteins suppress tumorigenesis remains unclear, although both conditions are associated with chromosome instability Here we show that the Fanconi anaemia proteins FANCD2 and FANCI specifically associate with common fragile site loci irrespective of whether the chromosome is broken Unexpectedly, these loci are frequently interlinked through BLM-associated ultra-fine DNA bridges (UFBs) even as cells traverse mitosis Similarly to fragile site expression, fragile site bridging is induced after partial inhibition of DNA replication We propose that, after replication stress, sister chromatids are interlinked by replication intermediates primarily at genetic loci with intrinsic replication difficulties, such as fragile sites In Bloom's syndrome cells, inefficient resolution of DNA linkages at fragile sites gives rise to increased numbers of anaphase UFBs and micronuclei containing fragile site DNA Our data have general implications concerning the contribution of fragile site loci to chromosomal instability and tumorigenesis

Functional–Anatomical Validation and Individual Variation of Diffusion Tractography-based Segmentation of the Human Thalamus

Abstract: Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.