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Biomedical subjects

M R Jones

Publications and source records attributed to M R Jones.

At least 19 recordsLinked to original sources
PubMed2006

Bloodstream infections in a secondary and tertiary care hospital setting.

BACKGROUND: Bloodstream infections (BSI) occurring in community and health-care settings vary with the patient group and treatment of underlying medical conditions. We studied the clinical infectious syndromes occurring in patients with positive blood cultures routinely obtained at a regional secondary and tertiary care hospital. METHODS: BSI were categorized as either community-acquired (C-BSI), or health-care-associated (H-BSI) acquired either as a (i) non-inpatient (outpatient) or (ii) hospital inpatient. Clinical information was collected prospectively during the 1-year study. RESULTS: There were 193 C-BSI and 230 H-BSI. The large majority of C-BSI were caused by bacterial pathogens susceptible to narrow-spectrum antibiotics, particularly in children. Cefuroxime was active against 90% of C-BSI isolates and 46% of H-BSI isolates, excluding anaerobes. Of all H-BSI, the 35% occurring in outpatients had a similar source, microbiological cause and bacterial susceptibilities to the inpatients. H-BSI were infrequently due to enterococci (4%), Candida (3%) or methicillin-resistant Staphylococcus aureus (0.4%). No BSI were due to vancomycin-resistant enterococci or extended-spectrum beta-lactamase producing Enterobacteriaciae. I.v. catheters, predominantly central lines, were the source of 60% of all H-BSI, mostly in haematology-oncology or neonatal patients. Mortality at 1 month was 12% overall for both C-BSI and H-BSI, varying markedly by underlying disease and increasing age (for C-BSI). CONCLUSION: In this population, C-BSI have remained susceptible to narrow-spectrum antibiotics, whereas H-BSI due to multiresistant organisms were rare. Obtaining a history of recent medical procedures is important for community patients presenting with a BSI.

Adolescent↗
PubMed2005

Animal models for the study of adenosine receptor function.

Adenosine receptors represent a family of G-protein coupled receptors that are ubiquitously expressed in a wide variety of tissues. This family contains four receptor subtypes: A1 and A3, which mediate inhibition of adenylyl cyclase; and A2a and A2b, which mediate stimulation of this enzyme. Currently, all receptor subtypes have been genetically deleted in mouse models except for the A2b adenosine receptor, and some have been overexpressed in selective tissues of transgenic mice. Studies involving these transgenic mice indicated that receptor levels are rate limiting, as effects were amplified upon increases in receptor level. The knockout models pointed to clusters of activities related to the physiologies of the cardiovascular and the nervous systems, which are either reduced or enhanced upon specific receptor deletion. Interestingly, the trend of effects on these systems is similar in the A1 and A3 adenosine receptor knockout mice and opposite to the effects observed in the A2a adenosine receptor knockout model. This review summarizes in vitro studies on pathways affected by each adenosine receptor, and primarily focuses on the above in vivo models generated to investigate the physiologic role of adenosine receptors. Furthermore, it illustrates the need for multiple adenosine receptor subtype deficiency studies in mice and the deletion of the A2b subtype.

Adenosine↗
PubMed2005

Rewiring photosynthesis: engineering wrong-way electron transfer in the purple bacterial reaction centre.

The purple bacterial reaction centre uses light energy to separate charge across the cytoplasmic membrane, reducing ubiquinone and oxidizing a c-type cytochrome. The protein possesses a macroscopic structural two-fold symmetry but displays a strong functional asymmetry, with only one of two available membrane-spanning branches of cofactors (the so-called A-branch) being used to catalyse photochemical charge separation. The factors underlying this functional asymmetry have been the subject of study for many years but are still not fully understood. Site-directed mutagenesis has been partially successful in rerouting electron transfer along the normally inactive B-branch, allowing comparison of the kinetics of equivalent electron transfer reactions on the two branches. Both the primary and secondary electron transfer steps on the B-branch appear to be considerably slower than their A-branch counterparts. The effectiveness of different mutations in rerouting electron transfer along the B-branch of cofactors is discussed.

Bacteria↗
PubMed2005

Lipids in and around photosynthetic reaction centres.

Reaction centres are membrane-embedded pigment-protein complexes that transduce the energy of sunlight into a biologically useful form. The most heavily studied reaction centres are the PS-I (Photosystem I) and PS-II complexes from oxygenic phototrophs, and the reaction centre from purple photosynthetic bacteria. A great deal is known about the compositions and structures of these reaction centres, and the mechanism of light-activated transmembrane electron transfer, but less is known about how they interact with other components of the photosynthetic membrane, including the membrane lipids. X-ray crystallography has provided high-resolution structures for PS-I and the purple bacterial reaction centre, and revealed binding sites for a number of lipids, either embedded in the protein interior or attached to the protein surface. These lipids play a variety of roles, including the binding of cofactors and the provision of structural support. The challenges of modelling surface-associated electron density features such as lipids, detergents, small amphiphiles and ions are discussed.

Crystallography, X-Ray↗
PubMed2005

Temporal and spatial organization of doctors' computer usage in a UK hospital department.

This paper describes the use of an application accessible via distributed desktop computing and wireless mobile devices in a specialist department of a UK acute hospital. Data (application logs, in-depth interviews, and ethnographic observation) were simultaneously collected to study doctors' work via this application, when and where they accessed different areas of it, and from what computing devices. These show that the application is widely used, but in significantly different ways over time and space. For example, physicians and surgeons differ in how they use the application and in their choice of mobile or desktop computing. Consultants and junior doctors in the same teams also seem to access different sources of patient information, at different times, and from different locations. Mobile technology was used almost exclusively during the morning by groups of clinicians, predominantly for ward rounds.

Computers↗
PubMed2005

Effects of grouping unfamiliar cohorts, high ambient temperature and stocking density on live performance of growing pigs.

Ninety-six crossbred intact male pigs (34.5 +/- 3.5 kg BW) were allocated by weight and vocalization score to a 2 x 2 x 2 dynamic experimental design including two stocking densities (1 or 2 m(2)/pig), two temperatures (22 degrees C and 30 degrees C), and two short groupings of unfamiliar cohorts (six pigs as one pig per group, and six pigs per group). The study was conducted over 8 wk, and live weight gain (WTG) and feed intake (FI; as-fed basis) were measured weekly. During the first week, pigs were housed in individual pens from four independent rooms. To group pigs, pen partitions were removed. Pigs were grouped in Rooms 2 and 3 from wk 2 to 4, and in Rooms 1 and 4 during wk 7. Temperature was increased from 22 degrees C to 30 degrees C in Rooms 1 and 2 during wk 4 and 7. Pen partitions were replaced in Rooms 2 and 3 at the end of wk 4 and in Rooms 1 and 4 at the end of wk 7 to return pigs to their individual pens. Grouping pigs decreased FI during wk 3 (15.08 +/- 0.43 vs. 14.03 +/- 0.41 kg P < 0.10), and during wk 7 (17.42 +/- 0.46 vs. 14.24 +/- 0.41 kg; P < 0.01). In addition, grouping had a negative effect (P < 0.001) on WTG at wk 3 (7.38 +/- 0.28 vs. 5.71 +/- 0.28 kg) and at wk 7 (6.70 +/- 0.26 vs. 2.99 +/- 0.26 kg). For grouped pigs, raising the temperature decreased (P < 0.01) WTG (7.49 +/- 0.29 vs. 6.41 +/- 0.29 kg during wk 4, and 3.37 +/- 0.38 vs. 2.62 +/- 0.38 kg during wk 7). Mean FI was decreased (P < 0.01) with the 30 degrees C treatment during wk 7 only (15.49 +/- 0.33 kg at 22 degrees C compared with 12.99 +/- 0.33 kg at 30 degrees C). Compensatory feed intake was evident after the treatments had ceased at wk 6, whereby previously heat-treated grouped pigs had a higher FI (17.97 +/- 0.45 kg) than the animals individually housed at 22 degrees C (12.99 +/- 0.33 kg). Stocking density effects were noted after the grouping and high temperature treatments had ceased. For instance, during wk 5, low-density-housed pigs grew faster (P < 0.001) than their high-density counterparts (9.04 +/- 0.38 vs. 7.49 +/- 0.29 kg). In conclusion, under the conditions of this study, the grouping of unfamiliar cohorts and high ambient temperature treatments had a detrimental effect on pig performance, and these effects were reversible.

Animal Husbandry↗
PubMed2003

A functional genomic analysis of cell morphology using RNA interference.

BACKGROUND: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. RESULTS: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. CONCLUSIONS: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

Animals↗
PubMed2003

"Computers can land people on Mars, why can't they get them to work in a hospital?" Implementation of an Electronic Patient Record System in a UK Hospital.

OBJECTIVES: This paper aims to describe and interpret the implementation of a hospital information system in a large UK hospital. METHODS: The paper is based on a longitudinal case study over a three-year period in which a cross section of hospital staff involved with the information system were interviewed. RESULTS AND CONCLUSIONS: Ambitious government targets for the use of Information Technology in the UK National Health Service sit alongside a history of notable project failures. The decision by a UK hospital to install an advanced, integrated electronic patient record system therefore faced conflicting demands and expectations. This paper suggests that its simple categorisation as either a success or failure is problematic. Rather, the differing viewpoints that lead some clinicians to express "disappointment" with its performance, while others described its features as "tremendous" and managers suggested that the system had become "taken for granted" are explored. A number of broader phenomena relating to the organisational processes surrounding information systems implementation are also identified.

Attitude of Health Personnel↗
PubMed2002

Evidence for direct learning curve for technique on change of cervical sampling device.

The recommended sampling device within the NHS Cervical Screening Programme is the Aylesbury spatula. A local decision was taken to decrease brush usage (either alone or in combination) by 50% from an initial level of 41.8%, with an initial inadequate smear rate of 9.93%. This was managed by controlling smear taking equipment through provision of smear taking kits. The monthly inadequate rate unexpectedly rose to 17.8% before dropping back to previous levels. Brush usage overall fell to 35.2%, with a corresponding increase in spatula use. The possible reasons for this are discussed. The facts suggest that these changes were directly linked, and that there is a learning curve with change of sampling device and that a rise in the inadequate rate should be expected under these circumstances.

Female↗
PubMed2001

Carotid angioplasty and stenting versus carotid endarterectomy: randomized trial in a community hospital.

OBJECTIVES: The goal of this study was to determine whether carotid angioplasty and stenting (CAS) is equivalent to carotid endarterectomy (CEA) in patients with symptomatic carotid stenosis >70% by a randomized, controlled trial in a community hospital. BACKGROUND: Carotid angioplasty and stenting has been suggested to be as effective as CEA for treatment of symptomatic carotid artery stenosis. METHODS: A total of 104 patients presenting with cerebrovascular ischemia ipsilateral to carotid stenosis were selected randomly for CEA or carotid stenting and followed for two years. RESULTS: Stenosis decreased to an average of 5% after CAS. The patency of the reconstructed artery remained satisfactory regardless of the technique as determined by sequential ultrasound. One death occurred in the CEA group (1/51); one transient ischemic attack occurred in the CAS group (1/53); no individual sustained a stroke. The perception of procedurally related pain/discomfort was similar. Hospital stay was similar, although the CAS group tended to be discharged earlier (mean = 1.8 days vs. 2.7 days). Complications associated with CAS prolonged hospitalization when compared with those sustaining a CEA-related complication (mean = 5.6 days vs. 3.8 days). Return to full activity was achieved within one week by 80% of the CAS group and 67% of the patients receiving CEA. Hospital charges were slightly higher for CAS. CONCLUSIONS: Carotid stenting is equivalent to CEA in reducing carotid stenosis without increased risk for major complications of death/stroke. Because of shortened hospitalization and convalescence, CAS challenges CEA as the preferred treatment of symptomatic carotid stenosis if a reduction in costs can be achieved.

Adult↗
PubMed2001

Human urotensin II increases coronary perfusion pressure in the isolated rat heart: potentiation by nitric oxide synthase and cyclooxygenase inhibition.

Urotensin II (U-II) is a cyclic peptide, recently cloned in man and present in cardiac tissue and arteries. The effects of human U-II (hU-II) on coronary perfusion pressure (CPP) were investigated in isolated rat hearts perfused retrogradely via the aorta at constant flow. hU-II produced a concentration-dependent increase in CPP (pEC50 8.6 +/- 0.3, n = 8), the maximum increase in CPP (12 +/- 4 mmHg) was obtained at 10(-7) M hU-II. At higher concentrations of hU-II CPP fell back towards baseline. Endothelin-1 produced a maximum increase in CPP of 63 +/- 11 mmHg within the concentration-range studied. Addition of the NO synthase inhibitor L N(G)nitro-arginine methyl ester (10(-4) M) and the cyclooxygenase inhibitor, indomethacin (10(-5) M) to the perfusion solution had no effect on the pEC50 value for hU-II, but significantly increased the maximum constriction (to 34 +/- 7 mmHg, n = 8, p < 0.05) and inhibited the later dilator response to hU-II. These results suggest that receptors for hU-II are present in the coronary vasculature and that smooth muscle contraction is modulated by the release of dilator factors, including NO and prostacyclin. Endothelial function is therefore likely to be of primary importance in modulating the coronary vasoconstrictor effects of hU-II in vivo.

Animals↗
PubMed2001

Photosynthesis: new light on biological oxygen production.

In oxygenic photosynthesis, a highly oxidising chlorophyll species strips electrons out of two water molecules, generating molecular oxygen as a waste product. A recent study has provided new insights into the structure of the molecular machinery responsible for biological oxygen production.

Crystallography, X-Ray↗
PubMed2001

Is there a conserved interaction between cardiolipin and the type II bacterial reaction center?

In a recent publication, the structural details of an interaction between the Rhodobacter sphaeroides reaction center and the anionic phospholipid diphosphatidyl glycerol (cardiolipin) were described (K. E. McAuley, P. K. Fyfe, J. P. Ridge, N. W. Isaacs, R. J. Cogdell, and M. R. Jones, 1999, Proc. Natl. Acad. Sci. U.S.A. 96:14706-14711). This was the first crystallographic description of an interaction between this biologically important lipid and an integral membrane protein and was also the first piece of evidence that the reaction center has a specific interaction with cardiolipin. We have examined the extent to which the residues that interact with the cardiolipin are conserved in other species of photosynthetic bacteria with this type of reaction center and discuss the possibility that this cardiolipin binding site is a conserved feature of these reaction centers. We look at how sequence variations that would affect the shape of the cardiolipin binding site might affect the protein-cardiolipin interaction, by modeling the binding of cardiolipin to the reaction center from Rhodopseudomonas viridis.

Amino Acid Sequence↗
PubMed2001

A comparative in vitro evaluation of the fermentation properties of prebiotic oligosaccharides.

AIMS: Comparison of in vitro fermentation properties of commercial prebiotic oligosaccharides. METHODS AND RESULTS: Populations of predominant gut bacterial groups were monitored over 24 h of batch culture through fluorescent in-situ hybridization. Short-chain fatty acid and gas production were also measured. All prebiotics increased the numbers of bifidobacteria and most decreased clostridia. Xylo-oligosaccharides and lactulose produced the highest increases in numbers of bifidobacteria whilst fructo-oligosaccharides produced the highest populations of lactobacilli. Galacto-oligosaccharides (GOS) resulted in the largest decreases in numbers of clostridia. Short-chain fatty acid generation was highest on lactulose and GOS. Gas production was lowest on isomalto-oligosaccharides and highest on inulin. CONCLUSIONS: The oligosaccharides differed in their fermentation characteristics. Isomalto-oligosaccharides and GOS were effective at increasing numbers of bifidobacteria and lactate whilst generating the least gas. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides comparative data on the properties of commercial prebiotics, allowing targeting of dietary intervention for particular applications and blending of oligosaccharides to enhance overall functionality.

Bacteria↗
PubMed2001

Pumping capacity of bacterial reaction centers and backpressure regulation of energy transduction.

Transduction of free-energy by Rhodobacter sphaeroides reaction-center-light-harvesting-complex-1 (RCLH1) was quantified. RCLH1 complexes were reconstituted into liposomal membranes. The capacity of the RCLH1 complex to build up a proton motive force was examined at a range of incident light intensities, and induced proton permeabilities, in the presence of artificial electron donors and acceptors. Experiments were also performed with RCLH1 complexes in which the midpoint potential of the reaction center primary donor was modified over an 85-mV range by replacement of the tyrosine residue at the M210 position of the reaction center protein by histidine, phenylalanine, leucine or tryptophan. The intrinsic driving force with which the reaction center pumped protons tended to decrease as the midpoint potential of the primary donor was increased. This observation is discussed in terms of the control of the energetics of the first steps in light-driven electron transfer on the thermodynamic efficiency of the bacterial photosynthetic process. The light intensity at which half of the maximal proton motive force was generated, increased with increasing proton permeability of the membrane. This presents the first direct evidence for so-called backpressure control exerted by the proton motive force on steady-state cyclic electron transfer through and coupled proton pumping by the bacterial reaction center.

Electron Transport↗
PubMed2001

Fermentation properties of gentio-oligosaccharides.

AIMS: To investigate the fermentation properties of gentio-oligosaccharides (GOS), as compared to fructo-oligosaccharides (FOS) and maltodextrin in mixed faecal culture. METHODS AND RESULTS: The substrates were incubated in 24 h batch culture fermentations of human faecal bacteria. Fluorescent in situ hybridization was used to determine changes in populations of bifidobacteria, lactobacilli, clostridia, bacteroides, streptococci and Escherichia coli. Gas and short-chain fatty acid (SCFA) production was also measured. GOS gave the largest significant increases in bifidobacteria, lactobacilli and total bacterial numbers during the incubations. However, FOS appeared to be a more selective prebiotic as it did not significantly stimulate growth of bacterial groups which were not probiotic in nature. GOS and maltodextrin produced the highest levels of SCFA. Lowest gas production was seen with GOS and highest with FOS. CONCLUSIONS: GOS possessed bifidogenic activity in vitro. Although fermentation of GOS was not as selective as FOS, gas production was lower. Gas production is often seen as an undesirable side effect of prebiotic consumption. SIGNIFICANCE AND IMPACT OF THE STUDY: The study has provided the first data on fermentation of GOS in mixed faecal culture. The study has also used molecular microbiology methods (FISH) to quantify bacterial groups. The data extend our knowledge of the selectivity of fermentation of oligosaccharides by the gut microflora.

Bacteria↗