Browsing by Author "Gray, Douglas T."

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    Are multimedia resources effective in life science education? A meta-analysis.
    (UK Centre for Bioscience, 2011-11) Rolfe, Vivien E.; Gray, Douglas T.
    Multimedia learning is widely used in life science education where the use of pictures and text can bring complex structures and processes to life. However the impact on academic performance and deeper understanding is not well documented. We therefore carried out a systematic review to evaluate the effectiveness of multimedia resources in tertiary level life science education. Comprehensive literature searches were conducted; studies were selected based on stringent pre-set criteria, and data were extracted for meta-analysis. In total, 17 studies were used in the meta-analyses with a total population of 2,290 students. The results show that, when used as a substitute for laboratory practicals, multimedia improved student learning gains assessed with an end-of-year examination, (mean difference 7.06, ±4.61). Although it did not improve short-term learning gains in this scenario, multimedia improved learning gains in 10 of the 16 sub-group comparisons made across all the studies. Overall, multimedia learning was more effective than many traditional educational methods although the numbers of studies included in the analysis were ultimately considered to be small due to many exclusions from the studies included in the analysis. Therefore, more good quality trials are required to evaluate a broader range of scenarios relevant to modern practices. Studies would benefit from being rigorous in design with good quality reporting of all aspects of methodology and study results.
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    Effects of Estrogen Receptor Modulators on Uterine Pathology and Gene Expression.
    (The Toxicologist CD, 2005) Gray, Douglas T.; Greaves, Peter; Styles, Jerry; White, Ian
    Tamoxifen, a selective estrogen receptor modulator (SERM), is an effective treatment for breast cancers. In the CD-1 mouse model, neonatal oral dosing with tamoxifen leads to the development of adenomyosis. Subcutaneous dosing with tamoxifen or 4-hydroxyestradiol leads to adenocarcinomas after 12 to 18 months. Both 4-hydroxyestradiol and tamoxifen can form DNA-reactive metabolites and may be involved in carcinogenesis of the uterus. We compared the uterotrophic response of these compounds and their effects on uterine pathology and gene expression. 14-day-old CD-1 female mice were orally dosed daily for 3 days with estradiol benzoate (1-100μg/kg), tamoxifen (250-5000μg/kg), or 4-hydroxyestradiol (76.3-1920μg/kg). After 4 days uterine weights were recorded, then sections processed for PCNA staining. Maximal uterotrophic doses for weight increase over controls (fold change ± s.d.) were: estradiol (100g/kg) 2.6 ± 0.003, 4-hydroxyestradiol (385g/kg) 6.7 ± 0.03 and tamoxifen (250g/kg) 2.6 ± 0.005. PCNA staining showed maximal cell proliferative effects at this time were not related to uterine weight increases. Estradiol inhibited the development of glandular epithelium, whereas tamoxifen was able significantly to increase the number of glands. Maximal uterotrophic dose of estradiol (100g/kg) was given orally to newborn CD1 mice on days 1 – 5 after birth and gene and pathological changes examined in the uterus at 3 months after dosing. No adenomyosis was seen. Gene expression changes showed up-regulation of typical estrogenic response genes including actb, sp1 while other genes such as ngf and spp1 were down-regulated. This study shows that neonatal estradiol treatment brings about long-term changes in gene expression in the absence of apparent pathological changes.
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    Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer.
    (Elsevier, 2005-03) Gray, Douglas T.; Green, A.; White, Ian; Styles, Jerry; Edwards, Richard; Smith, A.; Gant, T.; Greaves, Peter; Al-Azzawi, Farook
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    Pathology and Gene Expression in the Uteri of Mice Dosed with Oestradiol and Tamoxifen.
    (Toxicology, 2004) Gray, Douglas T.; Greaves, Peter; Styles, Jerry; White, Ian
    There is a marked difference in the development of uterine pathologies following administration of tamoxifen to neonatal mice by different routes. Oral dosing causes adenomyosis while subcutaneous administration results in cancer. In order to establish if this compound has similar estrogenic agonist effects by the two routes, a standard uterotrophic assay was set up in immature mice to compare the effects of tamoxifen and estradiol by these two routes. In this study mice were dosed with oral estradiol to establish the effects of this compound on the development of adenomyosis and changes in gene expression after 3 months in comparison to tamoxifen. For uterotrophic assays, 14 day old CD-1 female mice were dosed by oral or subcutaneous routes daily for 3 days in groups of 4 with -estradiol 3-benzoate at either 0, 1, 5, 10, 50, or 100g/kg. b.w.; or with tamoxifen at either 0, 0.25, 0.5, 1, 2.5 or 5mg/kg. b.w.. Animals received oral doses at 5l/g bodyweight. Subcutaneous doses were administered at 5l/g bodyweight. Animals were killed on the fourth day and uteri were removed, weighed and fixed in Carnoy’s. For the 3-month pathology study, CD-1 female mice were dosed on days 2-5 after birth with oral -estradiol 3-benzoate at the same doses used for the uterotrophic assays with 12 mice per dosing level and 40 control mice. Mice were culled after 3 months and uteri were either fixed in Carnoy’s for pathology or snap frozen and stored in liquid nitrogen for RNA isolation. Changes in gene expression were analysed using cDNA arrays, essentially described elsewhere (Turton, 2001) from 25g total RNA. Uterotrophic assays of estradiol showed that uterine weight, expressed as a percentage of total body weight, increased in response to subcutaneous administration in a dose dependent manner with a maximal response at 50g/kg. b.w. (0.56%, ± 0.12 S.D.). In contrast orally administered estradiol was less effective, with a positive effect only at 50g /kg. b.w. (0.35%, ± 0.06 S.D.) and 100g/Kg (0.39%, ± 0.04 S.D.). Tamoxifen gave an equally positive uterotrophic effect at both the lowest (0.25mg/kg) and highest (5mg/kg) doses with a slightly greater effect following oral administration. The uteri of all animals were normal as assessed by histopathology. Gene microarrays identified NGFa as a gene of interest in which expression was increased after tamoxifen treatment and decreased after estradiol treatment. These results show that both compounds are reaching the uterus and that the development of adenomyosis is not due to metabolic effects. Results of the 3 month study show that adenomyosis does not develop in the uteri of estradiol treated mice in contrast to tamoxifen treated mice. Therefore it is reasonable to suggest that adenomyosis is not simply the result of an estrogen agonist action of tamoxifen on the developing uterine tissue.
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    Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica.
    (American Society of Microbiology, 2004-10) Gray, Douglas T.; Eaves, D. J.; Randall, L.; Buckley, A.; Woodward, M. J.; White, A. P.; Piddock, L. J.
    Salmonella enterica isolates (n = 182) were examined for mutations in the quinolone resistance-determining region of gyrA, gyrB, parC, and parE. The frequency, location, and type of GyrA substitution varied with the serovar. Mutations were found in parC that encoded Thr57-Ser, Thr66-Ile, and Ser80-Arg substitutions. Mutations in the gyrB quinolone resistance-determining region were located at codon Tyr420-Cys or Arg437-Leu. Novel mutations were also found in parE encoding Glu453-Gly, His461-Tyr, Ala498-Thr, Val512-Gly, and Ser518-Cys. Although it is counterintuitive, isolates with a mutation in both gyrA and parC were more susceptible to ciprofloxacin than were isolates with a mutation in gyrA alone.