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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 19 recordsLinked to original sources
PubMed2007

137Cs and 90Sr in live and dead reindeer lichens (genera Cladonia) from the "Kraton-3" underground nuclear explosion site.

The contents of 137Cs and 90Sr have been determined in 29 samples of live and dead reindeer lichens (genera Cladonia) collected at the "Kraton-3" underground nuclear explosion site (65.9 degrees N 112.3 degrees E, event year--1978) in Yakutia, Russia in 2002. The area contamination was within the range of 0.36-700 and 0.13-770 kBq m(-2) for 137Cs and 90Sr, respectively. The dead organisms were on average much more contaminated than the live ones. Vertical fractionation of the live lichen carpet demonstrated maximal activity concentrations of both radionuclides in the lower older section of the plants, while for the dead lichens the maximal activity concentrations of 137Cs were detected in the upper part. The vertical distribution of 90Sr was more or less homogeneous in the cushions of dead lichens. Elevated levels of 137Cs and 90Sr activity concentrations were also detected in the re-establishing young lichens growing over the residua of some dead lichens.

Animals↗
PubMed2006

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.

BACKGROUND AND PURPOSE: Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated. EXPERIMENTAL APPROACH: Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgammaS assay and transfected cells. KEY RESULTS: Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P>0.05 each; n=4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 microM to facilitate EFS-evoked contractions of the stomach (increases were 42.7+/-7.8% and 21.2+/-5.0 % in the absence and presence of obestatin 1 nM; P<0.05; n=12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT(4) receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3+/-14.0% and 42.6+/-8.7% in the absence and presence of 1000 nM obestatin; n=10). Obestatin (up to 10 microM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg(-1) min(-1)) had no effects. Obestatin (2500 pmol kg(-1) min(-1), starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg(-1) min(-1)) to shorten MMC cycle time. CONCLUSIONS AND IMPLICATIONS: Obestatin has little ability to modulate rat GI motility.

Animals↗
PubMed2006

Genetic variance modifies apoptosis susceptibility in mature oocytes via alterations in DNA repair capacity and mitochondrial ultrastructure.

Although the identification of specific genes that regulate apoptosis has been a topic of intense study, little is known of the role that background genetic variance plays in modulating cell death. Using germ cells from inbred mouse strains, we found that apoptosis in mature (metaphase II) oocytes is affected by genetic background through at least two different mechanisms. The first, manifested in AKR/J mice, results in genomic instability. This is reflected by numerous DNA double-strand breaks in freshly isolated oocytes, causing a high apoptosis susceptibility and impaired embryonic development following fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis and improves embryonic development. The second, manifested in FVB mice, results in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with cytochrome c release and a high apoptosis susceptibility, the latter of which is suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of 'normal' mitochondria. Therefore, background genetic variance can profoundly affect apoptosis in female germ cells by disrupting both genomic DNA and mitochondrial integrity.

Animals↗
PubMed2006

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Adult↗
PubMed2006

The impact of protein characterization in structural proteomics.

Protein characterization plays a role in two key aspects of structural proteomics. The first is the quality assessment of the produced protein preparations. Obtaining well diffracting crystals is one of the major bottlenecks in the structure-determination pipeline. Often, this is caused by the poor quality of the protein preparation used for crystallization trials. Hence, it is essential to perform an extensive quality assessment of the protein preparations prior to crystallization and to use the results in the evaluation of the process. Here, a protein-production and crystallization strategy is proposed with threshold values for protein purity (95%) and monodispersity (85%) below which a further optimization of the protein-production process is strongly recommended. The second aspect is the determination of protein characteristics such as domains, oligomeric state, post-translational modifications and protein-protein and protein-ligand interactions. In this paper, applications and new developments of protein-characterization methods using MS, fluorescence spectroscopy, static light scattering, analytical ultracentrifugation and small-angle X-ray scattering within the EC Structural Proteomics in Europe contract are described. Examples of the application of the various methods are given.

Crystallization↗
PubMed2006

Probabilistic biokinetic modelling of radiocaesium uptake in Arctic seal species: verification of modelled data with empirical observations.

The necessity to provide information about radionuclide concentrations in Arctic marine species has been heightened in recent years due to a number of accidents in Arctic regions involving nuclear vessels and the presence of a large number of potential radioactive contamination sources. The provision for such information is largely dependent on the use of radionuclide uptake and transfer models. The uptake of radionuclides in Arctic seal species in this study has been modelled using a probabilistic biokinetic approach. In this paper, model results are compared with empirical data from relevant samples taken within the Arctic region. Results indicate that the model performs well when estimating concentrations of (137)Cs in two seal species for both median values and reproduction of the distribution of data values, but not as well for a third seal species. Likely factors affecting the results are the probability density functions used for the input parameters.

Animals↗
PubMed2006

CytoregR inhibits growth and proliferation of human adenocarcinoma cells via induction of apoptosis.

BACKGROUND: Cancer is one of the devastating neovascular diseases that incapacitate so many people the world over. Recent reports from the National Cancer Institute indicate some significant gain therapy and cancer management as seen in the increase in the 5-year survival rate over the past two decades. Although near-perfect cure rate have been reported in the early-stage disease, these data reveal high recurrence rate and serious side effects including second malignancies and fatalities. Most of the currently used anticancer agents are only effective against proliferating cancer cells. Thus attention has been focused on potential anti-cancer agents capable of killing cancer cells independent of the cell cycle state, to ensure effective elimination of most cancer cells. The objective of this study was to test the chemosensitivity and potential mechanism of action of a novel cancer drug, CytoregR, in a panel of human cancer cells. METHODS: the study was performed using a series of bioassays including Trypan blue exclusion, MTS Growth inhibition, LDH-cytotoxicity, TUNEL-Terminal DNA fragmentation Apoptosis Assay, and the Caspase protease CPP32 activity assays. RESULTS: CytoregR induced significant dose- and time-dependent inhibition of growth in all the cells; with significant differences in chemosensitivity (P < 0.05) between the target cells becoming more apparent at 48 hr exposure. CytoregR showed no significant effect on normal cells relative to the tumor cells. Growth inhibition in all the cells was due to induction of apoptosis at lower concentrations of cytoregR (> 1:300). CytoregR-induced caspase protease-3 (CPP32) activation significantly and positively correlated with apoptosis induction and growth inhibition; thus implicating CPP32 as the principal death pathway in cytoregR-induced apoptosis. CONCLUSION: CytoregR exerted a dose-and time-dependent growth inhibitory effect in all the target cells through induction of apoptosis via the CPP32 death pathway, independent of hormonal sensitivity of the cells. The present data indicate that not only could CPP32 provide a potential target for regulation of cytoregR-induced apoptosis but also that cytoregR could play a significant role in chemotherapeutic regimen in many human malignant tumors.

Journal Article↗
PubMed2006

A Bayesian approach to analysing the cost-effectiveness of two primary care interventions aimed at improving attendance for breast screening.

AIMS: To assess the cost-effectiveness of two primary care interventions, a letter and a flag, aimed at improving attendance for breast screening among (i) all women invited for breast screening and (ii) non-attenders. METHODS: A probabilistic decision analytic model was developed using Markov chain Monte Carlo simulation implemented in WinBUGS. The model was populated using economic and effectiveness data collected alongside two randomised controlled trials. RESULTS: For all women invited, the incremental cost-effectiveness ratio (ICER) for the letter compared with no intervention is 27 pounds per additional attendance, and the ICER for the combined letter and flag intervention compared to the letter alone is 171 pounds. The corresponding ICERs for non-attenders are 41 pounds and 90 pounds. The flag intervention is an inefficient option in both settings. A large proportion of the costs fall on the practices (25-67%), depending on the intervention and target population. The total costs incurred do not, however, seem prohibitive. Expected value of perfect information suggests that there is greater value in carrying out further research on the intervention implemented among all women invited for breast screening rather than on non-attenders. CONCLUSIONS: The flag intervention alone does not appear to be an efficient option. The choice between the letter and both interventions combined is subjective, depending on the willingness to pay for an additional screening attendance.

Bayes Theorem↗
PubMed2006

Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate.

OBJECTIVE: This study aimed to determine the extent of agreement between central venous and arterial values for pH, bicarbonate, base excess, and lactate in a group of intensive care unit (ICU) patients. METHODS: A prospective study of a convenience sample of patients deemed by their treating doctor to require blood gas analysis as part of their clinical care in ICU. It compared pH, bicarbonate, base excess and lactate on arterial and central venous samples taken within five minutes of each other. Data were analysed using bias (Bland-Altman) methods. RESULTS: A total of 168 matched sample pairs from 110 patients were entered into the study. All variables showed close agreement. The mean difference between arterial and venous values of pH was 0.03 pH units, for bicarbonate 0.52 mmol/l, for lactate 0.08 mmol/l, and for base excess 0.19 mmol/l. All showed acceptably narrow 95% limits of agreement. CONCLUSION: Central venous pH, bicarbonate, base excess, and lactate values showed a high level of agreement with the respective arterial values, with narrow 95% limits of agreement. These results suggest that venous values may be an acceptable substitute for arterial measurement in this clinical setting.

Acid-Base Imbalance↗
PubMed2006

Prevalence of the LRRK2 G2019S mutation in a UK community based idiopathic Parkinson's disease cohort.

The LRRK2 G2019S mutation is the commonest genetic cause of Parkinson's disease (PD) identified to date, although estimates of its prevalence in idiopathic disease vary considerably. Our objectives were to determine G2019S mutation frequency in an unselected, community based cohort of idiopathic PD cases from the UK and to describe phenotypic characteristics among carriers. The mutation was present in two of 519 cases (0.4%) and none of 887 control individuals. The true prevalence of the mutation in idiopathic disease, its penetrance, and the phenotypic heterogeneity of associated cases have important implications for genetic screening in the clinical field.

Adult↗
PubMed2006

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Case-Control Studies↗
PubMed2006

Exploring the views of second-year Foundation Programme doctors and their educational supervisors during a deanery-wide pilot Foundation Programme.

AIM: To explore the views of second-year Foundation Programme doctors (F2s) and their educational supervisors taking part in a deanery-wide pilot Foundation Programme, in order to gain an understanding of their perceptions of the available learning experiences, support and supervision. METHODS: 20 semi-structured interviews were undertaken with randomly selected F2 doctors and educational supervisors participating in the deanery-wide pilot Foundation Programme. RESULTS: F2 trainees received appropriate and sufficient support and supervision from a variety of sources during their placements; however, it was believed that additional training of educational supervisors was required. Trainees reported some problems with the perception of the role of an F2; further understanding of the purpose and role of the F2 programme is required at trust level. The portfolio was viewed positively as a record and a learning tool, but was thought to be too bureaucratic. Trainees believed that it was more beneficial to their careers to take part in a foundation programme as opposed to a traditional senior house officer post, but both trainees and educational supervisors expressed some concerns about the generic nature of some skills F2s were expected to acquire. CONCLUSIONS: This evaluation has highlighted successful aspects of the Foundation Programme, particularly with regard to the level of support and range of experiences provided for trainees. Issues of concern to both trainees and educational supervisors have been identified, which require additional understanding.

Attitude of Health Personnel↗