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Biomedical subjects

Phil Jones

Publications and source records attributed to Phil Jones.

17 recordsLinked to original sources
PubMed2007

Role for amplification and expression of glypican-5 in rhabdomyosarcoma.

Overexpression of genes, through genomic amplification and other mechanisms, can critically affect the behavior of tumor cells. Genomic amplification of the 13q31-32 region is reported in many tumors, including rhabdomyosarcomas that are primarily pediatric sarcomas resembling developing skeletal muscle. The minimum overlapping region of amplification at 13q31-32 in rhabdomyosarcomas was defined as containing two genes: Glypican-5 (GPC5) encoding a cell surface proteoglycan and C13orf25 encompassing the miR-17-92 micro-RNA cluster. Genomic copy number and gene expression analyses of rhabdomyosarcomas indicated that GPC5 was the only gene consistently expressed and up-regulated in all cases with amplification. Constitutive overexpression and knockdown of GPC5 expression in rhabdomyosarcoma cell lines increased and decreased cell proliferation, respectively. A correlation between expression levels of nascent pre-rRNA and GPC5 (P = 0.001), but not a C13orf25 transcript containing miR-17-92, in primary samples supports an association of GPC5 with proliferative capacity in vivo. We show that GPC5 increases proliferation through potentiating the action of the growth factors fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and Wnt1A. GPC5 enhanced the intracellular signaling of FGF2 and HGF and altered the cellular distribution of FGF2. The mesoderm-inducing effect of FGF2 and FGF4 in Xenopus blastocysts was also enhanced. Our data are consistent with a role of GPC5, in the context of sarcomagenesis, in enhancing FGF signaling that leads to mesodermal cell proliferation without induction of myogenic differentiation. Furthermore, the properties of GPC5 make it an attractive target for therapeutic intervention in rhabdomyosarcomas and other tumors that amplify and/or overexpress the gene.

Amino Acid Sequence↗
PubMed2005

Notch signaling regulates the differentiation of post-mitotic intestinal epithelial cells.

The intestinal epithelium comprises differentiated cells of four lineages maintained by precursor cells. As the Notch pathway controls the fate of proliferating cells in many systems, we investigated the effect of conditional expression of an activated Notch mutant in intestinal epithelium. An increase in the number of goblet cells occurs within 8 h of induction, due to an effect of Notch on post-mitotic cells, not on precursors. This observation broadens the role of Notch into controlling postmitotic differentiation and indicates that the composition of the epithelium is not solely determined by progenitor cells.

Animals↗
PubMed2005

Uranium speciation in moorland river water samples: a comparison of experimental results and computer model predictions.

An on-line method has been developed for separating inorganic and organic bound uranium species present in river water samples. The method utilised a small chelating resin (Hyphan) column incorporated into the sample introduction manifold of an ICP-MS instrument. The method was evaluated for samples from rivers on Dartmoor (Devon, UK), an area of granite overlain with peat bogs. The results indicate that organic-uranium species form a major proportion (80%) of the total dissolved uranium present. Further work with synthetic water samples indicated that the level of dissolved organic carbon played a greater role in determining the level of organic-uranium species than did sample pH. Computer models for the water samples were constructed using the WHAM program (incorporating uranium data from the Nuclear Energy Agency Thermochemical Database project) in order to predict the levels of organic-uranium species that would form. By varying the proportion of humic and fulvic acids used in the humic component, predictions within 10% of the experimental results were obtained. The program did exhibit a low bias at higher pH values (7.5) and low organic carbon concentrations (0.5 microg ml(-1)), but under the natural conditions prevalent in the Dartmoor water samples, the model predictions were successful.

Benzopyrans↗
PubMed2005

Effect of difficulty affording health care on health status after coronary revascularization.

BACKGROUND: An objective of the United States' Healthy People 2010 Initiative is to eliminate disparities based on socioeconomic status. We assessed the effect of difficulty affording health care on the health status (symptoms, function, and quality of life) of patients treated with percutaneous coronary intervention or CABG. METHODS AND RESULTS: A consecutive, single-center cohort of 480 patients undergoing coronary revascularization received the Seattle Angina Questionnaire at the time of their procedure and at subsequent monthly intervals for 6 months. At baseline, patients who reported somewhat of a burden to a severe burden in affording health care had significantly lower scores on the Seattle Angina Questionnaire (mean+/-SD) with respect to angina (55+/-29 versus 68+/-25, P<0.0001), physical limitation (55+/-26 versus 72+/-24, P<0.0001), and quality of life (46+/-22 versus 56+/-22, P<0.0001) than those who did not perceive healthcare costs to be burdensome. Although both groups of patients improved after revascularization, poorer health status persisted among those with difficulty affording health care after percutaneous coronary intervention (6-month mean+/-SE: angina 79+/-2.5 versus 88+/-1.9, P=0.002; physical function 61+/-2.7 versus 80+/-2.0, P<0.0001; quality of life 67+/-2.4 versus 82+/-1.8, P<0.0001) but not after CABG (angina 91+/-2.5 versus 93+/-1.6, P=0.47; physical function 75+/-3.4 versus 81+/-2.2, P=0.13; quality of life 84+/-3.1 versus 84+/-2.0, P=0.81). Similar differences remained after adjustment for demographic and clinical characteristics. CONCLUSIONS: Patients reporting difficulty affording health care have worse health status at the time of coronary revascularization. A persistent disparity exists after percutaneous but not surgical revascularization. Additional inquiry into the mechanism of this disparity is needed so that the goals of equitable health care, irrespective of treatment strategy, can be achieved.

Aged↗
PubMed2005

Further steps in standardisation. Report of the second annual Proteomics Standards Initiative Spring Workshop (Siena, Italy 17-20th April 2005).

The spring workshop of the HUPO-PSI convened in Siena to further progress the data standards which are already making an impact on data exchange and deposition in the field of proteomics. Separate work groups pushed forward existing XML standards for the exchange of Molecular Interaction data (PSI-MI, MIF) and Mass Spectrometry data (PSI-MS, mzData) whilst significant progress was made on PSI-MS' mzIdent, which will allow the capture of data from analytical tools such as peak list search engines. A new focus for PSI (GPS, gel electrophoresis) was explored; as was the need for a common representation of protein modifications by all workers in the field of proteomics and beyond. All these efforts are contextualised by the work of the General Proteomics Standards workgroup; which in addition to the MIAPE reporting guidelines, is continually evolving an object model (PSI-OM) from which will be derived the general standard XML format for exchanging data between researchers, and for submission to repositories or journals.

Mass Spectrometry↗
PubMed2005

Derivatisation of carboxylic acid groups in pharmaceuticals for enhanced detection using liquid chromatography with electrospray ionisation tandem mass spectrometry.

Tris(2,4,6-trimethoxyphenyl)phosphonium propylamine bromide (TMPP) has been used for the derivatisation of maleic, fumaric, sorbic and salicylic acids to facilitate determination using liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS) in positive ion mode. Detection limits, achieved using multiple reaction monitoring mode, were 2, 4, 0.4 and 540 fmol (5 muL injection) for derivatised fumaric, sorbic, maleic and salicylic acids, respectively. In comparison, detection limits achieved in negative ion mode for the underivatised acids were 24, 51, 2, and 117 fmol, respectively. The method was successfully used for the determination of sorbic acid in a sample of Panadol. The derivatisation of salicylic acid was not as successful, probably due to poor reaction efficiency.

Acetaminophen↗
PubMed2005

'Candidatus Phytoplasma graminis' and 'Candidatus Phytoplasma caricae', two novel phytoplasmas associated with diseases of sugarcane, weeds and papaya in Cuba.

During 2003, surveys of sugarcane yellow leaf disease and papaya bunchy top-like disease were carried out on plantations in Havana province, Cuba, to determine the roles of weeds and Auchenorrhyncha insects in the epidemiology of these diseases. More than 250 plant and insect samples were collected and indexed by using a nested PCR for phytoplasma 16S rDNA with the generic primer pairs P1/P7 and R16F2n/R16R2. The PCR products were further characterized by restriction fragment length polymorphism using HaeIII, AluI, Sau3AI, Tru9I, HhaI, HpaII and TaqI endonucleases, giving patterns that distinguished them from those of the other reference phytoplasmas analysed. Phylogenetic analysis of 16S rRNA gene sequences identified the phytoplasmas present in sugarcane (Saccharum officinarum L.), Cynodon dactylon L., Conyza canadensis L. Cronq., Sorghum halepense L. Pers., Macroptilium lathyroides L. Urb., Saccharosydne saccharivora (Westwood) and Cedusa spp., and those in papaya (Carica papaya L.) and Empoasca papayae, as two novel provisional phytoplasma species. We propose that these phytoplasmas should be given Candidatus status, as 'Candidatus Phytoplasma graminis' and 'Candidatus Phytoplasma caricae', respectively.

Base Sequence↗
PubMed2004

Tricuspid annuloplasty significantly reduces early tricuspid regurgitation after biatrial heart transplantation.

BACKGROUND: The incidence of tricuspid annuloplasty (TR) observed early after cardiac biatrial implantation is unpredictable and in our experience not infrequently problematic. Although the bicaval method of implant may reduce the incidence of TR, its benefit has not been conclusively documented. METHODS: In an attempt to reduce the incidence of TR observed early after cardiac transplantation, 25 consecutive patients undergoing cardiac transplantation received donor heart tricuspid annuloplasty (TA) with either a DeVega or Ring technique. Early transthoracic echocardiograms were analyzed and compared with an immediately prior and consecutive cohort of 25 patients undergoing transplantation without TA. The biatrial technique of cardiac transplantation with a Cabrol modification was used for donor heart implant in both groups. Echocardiograms obtained 5 days after cardiac transplantation were reviewed in blinded fashion. TR was scored 0 = none, 1 = mild, 2 = moderate, and 3 = severe. RESULTS: Donor and recipient characteristics were not different between groups. No hospital deaths occurred in either group. Patients undergoing transplantation without TA had a higher TR score, 1.3 (range 0-3), than did patients with TA, 0.7 (range 0-1.5, p = 0.002). Moderate or severe TR was present in 8 of 25 patients without TA compared with 0 of 25 patients with TA (p = 0.004). No patients required permanent pacemaker. CONCLUSIONS: TA can significantly reduce the incidence of early postoperative TR after biatrial cardiac transplant without adding to the complexity of operation.

Echocardiography↗
PubMed2003

Dithizone derivatives as sensitive water soluble chromogenic reagents for the ion chromatographic determination of inorganic and organo-mercury in aqueous matrices.

Water-soluble sulfonate and the novel carboxylate analogues of dithizone, combined with ion interaction chromatography on a Dionex Acclaim 120 C18 silica column (250 x 4.6 mm id) with an eluent consisting of 10 mM tetrabutylammonium bromide and 60:40 methanol:water, have been developed as highly sensitive chromogenic ligands for the quantitative isocratic determination of inorganic and organo-mercury compounds in aqueous matrices in under 12 min. Using an optimised post column reagent system containing 0.65 mM dye, 0.5% Triton X-100 and 50 mM sodium hydroxide, good linearity (0-7.5 mg L(-1) R2 > 0.999), reproducibility using peak area measurements (RSD 0.69-1.38%, n = 8), and limits of detection (4-12 microg L(-1)) were achieved for methyl mercury, inorganic mercury and phenyl mercury.

Chelating Agents↗
PubMed2003

Factors relating to patients' reports about hospital care for coronary heart disease in England.

OBJECTIVES: All health care providers in England are required to conduct surveys of their patients' experience of health care. Data from such surveys contribute to the 'star rating' performance indicators. However, there are concerns that these subjective measures may be influenced more by characteristics of patients than by true variations in the quality of care. The purpose of this paper is threefold: to determine the relationship between demographic characteristics and an index measure of patients' reported experience; to explore the extent to which patients' experiences may be accounted for by the particular National Health Service (NHS) trust they attended; and to assess how meaningful a summary index is in terms of its ability to discriminate between providers. METHODS: Data from patients in the National Survey of National Health Service Patients treated for coronary heart disease in 194 NHS trusts. Patients were sent questionnaires after discharge, with a covering letter and a prepaid stamped addressed envelope. Up to two reminders were sent to non-responders. Multi-level linear regression models were used to estimate the extent to which patients' experiences differed between trusts and the association of demographic variables with the summary index. RESULTS: In total, 116,872 patients were sent questionnaires, but 3399 proved to be ineligible for the survey. Responses were gained from 84,310 (74.3% of eligible respondents). Age and sex were most strongly associated with reported patients' experiences. However, the actual impact of age and sex on patients' experience is small, accounting for less than 3% of the variance. The proportion of the variance that was accounted for by the hospital trust in which patients were treated was only 5%. CONCLUSIONS: Demographic characteristics do not appear to account for differences between hospital trusts in patients' experience of health care. However, there is considerable variation in patients' experience within each provider. This would suggest that summary indices of patients' experience should not be used to rank providers, although detailed information from patient surveys have a useful role in determining priorities for quality improvement within individual hospitals and for assessing changes over time.

Adult↗
PubMed2002

Development of a virtual screening method for identification of "frequent hitters" in compound libraries.

A computer-based method was developed for rapid and automatic identification of potential "frequent hitters". These compounds show up as hits in many different biological assays covering a wide range of targets. A scoring scheme was elaborated from substructure analysis, multivariate linear and nonlinear statistical methods applied to several sets of one and two-dimensional molecular descriptors. The final model is based on a three-layered neural network, yielding a predictive Matthews correlation coefficient of 0.81. This system was able to correctly classify 90% of the test set molecules in a 10-times cross-validation study. The method was applied to database filtering, yielding between 8% (compilation of trade drugs) and 35% (Available Chemicals Directory) potential frequent hitters. This filter will be a valuable tool for the prioritization of compounds from large databases, for compound purchase and biological testing, and for building new virtual libraries.

Databases, Factual↗
PubMed2002

The effect of thermodynamic data on computer model predictions of uranium speciation in natural water systems.

Computer models have found widespread application in order to help elucidate and predict changes in environmental systems. One such application is the prediction of trace metal speciation in aqueous systems. This is achieved by solving a set of non-linear equations involving equilibrium constants for all the components in the system, within mass and charge balance constraints. In this study a comparison of the predicted uranium speciation from two computer programs, WHAM and PHREEQCI, is used to illustrate the effect variations in thermodynamic data can have on the models produced. Using the original thermodynamic data provided with the models, WHAM predicted the UO2(2+) ion as the major species (84%) while PHREEQCI predicted UO2(HPO4)2(2-) as the major species (86%). Substituting uranium data from the Nuclear Energy Agency Thermochemical Database project (NEA-TDB) into both programs produced similar results from each program, with UO2F+ predicted to dominate (68%) in a groundwater sample. Natural water samples often contain humic substances. The possible interaction of such substances with uranium was also modelled. The WHAM program includes a discreet site electrostatic humic substance model, however in order to use the PHREEQCI program to model humic substance interactions, a 'model fulvic acid' dataset was added to the program. These models predicted 85 to 98% uranium-humic substance species at neutral pH. This indicates that humic substances do need to be taken into account when modelling uranium speciation in natural water samples.

Computer Simulation↗
PubMed2002

Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study).

BACKGROUND: Although quantification of the impact of treatment on survival remains the cornerstone of clinical research, the assessment of a broader range of disease outcomes is growing increasingly important. This manuscript provides an overview of the considerations made regarding quantification of a range of clinical and economic outcomes in the EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study) study, a 6200-patient, randomized, controlled trial of aldosterone blockade in patients with heart failure as a complication of acute myocardial infarction. METHODS AND RESULTS: Relevant clinical outcomes include disease progression (mortality, hospitalization), health status (symptoms, functioning, and quality of life), and costs. The primary hypothesis for the quality of life component of EPHESUS is that eplerenone will improve health status as defined by the Kansas City Cardiomyopathy Questionnaire summary score. In addition to the Kansas City Cardiomyopathy Questionnaire, the Short Form-12, the EuroQOL, the Medical Outcomes Study-Depression Scale and an Anxiety measure will be collected throughout the trial. Health care resource utilization including hospitalizations, emergency room visits, outpatient procedures and tests, and medications will also be collected. Analyses will estimate and describe the effect of aldosterone blockade on costs over time. If both the clinical effect and costs are greater for patients receiving aldosterone blockade, then eplerenone's cost-effectiveness will be estimated. CONCLUSION: The EPHESUS trial has been designed to quantify a wide range of clinical outcomes. This broad range of data will allow a comprehensive assessment of the potential benefits of aldosterone blockade on patient health status and costs.

Antihypertensive Agents↗