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Biomedical subjects

N G Powell

Publications and source records attributed to N G Powell.

9 recordsLinked to original sources

Human papillomavirus infection: an anonymous prevalence study in South Wales, UK.

The objective of this study was to describe human papillomavirus (HPV) prevalence in South Wales in relation to age, cytology and social deprivation. This was an unlinked, prospective, anonymous, population-based study. DNA was purified from 1911 liquid-based cytology samples (mean age 37.7 years, cytology 93.2% negative, social deprivation average score 17.9) using quality assured techniques and the presence of virus determined by PCR-Enzyme Immuno Assay (PCR-EIA). 209 (10.9%) samples contained high-risk (HR) HPV infection of which 36.4% had multiple HR-HPV types. The most frequent HR types were HPV 16 (19.6%), HPV 35 (9.5%), HPV 66 (9.2%), HPV 59 (8.5%) and HPV 56 (7.6%). There was a strong association between HPV infection and cytological abnormality. Significantly more HR-HPV infections were detected in women under the age of 30 years (68.9% of all HR-HPV infections Fisher's exact test P=0.0001) compared to 30 years and above. There was no difference in HPV prevalence between different socioeconomic groups. The data presented suggest a different HPV type distribution in South Wales in comparison to that reported for other populations.

Adult↗

Roles for Gcn5p and Ada2p in transcription and nucleotide excision repair at the Saccharomyces cerevisiae MET16 gene.

Chromatin structure, transcription and repair of cyclobutane pyrimidine dimers at the MET16 gene of wild type, gcn5Delta and ada2Delta Saccharomyces cerevisiae cells were studied under repressing or derepressing conditions. These two components of the SAGA/ADA chromatin remodelling complexes are expendable for the basal transcription of MET16 but are mandatory for its full transcription induction. Despite their influence on transcription neither protein induces major changes in MET16 chromatin structure, but some minor ones occur. Repair at the coding region of the transcribed strand is faster than repair at non-transcribed regions in all strains and either growth condition. Moreover, the more MET16 is transcribed the faster the repair. The data show that by changing the transcription extent the rate of repair at each DNA strand is altered in a different way, confirming that repair at this locus is strongly modulated by its chromatin structure and transcription level. Deletion of GCN5 or ADA2 reduces repair at MET16. The results are discussed in light of the current understanding of Gcn5p and Ada2p functions, and they are the first to report a role for Ada2p in the nucleotide excision repair of the regulatory and transcribed regions of a gene.

Chromatin↗

Investigation of loss of heterozygosity and SNP frequencies in the RET gene in papillary thyroid carcinoma.

In both medullary carcinoma and papillary carcinoma of the thyroid, altered expression of the RET gene is implicated in tumorigenesis. Recent studies suggest that loss of heterozygosity (LOH) at the G691S SNP may be associated with tumors from patients with a history of radiation exposure. We investigated LOH for three RET SNPs (G691S, S904S, and L769L) in tumor and normal tissue from 46 patients from Ukraine and Belarus who were exposed to radioactive fallout following the Chernobyl nuclear accident and were operated for papillary thyroid carcinoma between 1995 and 2000. Normal tissue from 28 patients was heterozygous for at least one SNP; DNA from the corresponding tumor samples was also heterozygous, indicating that no LOH had taken place. To assess SNP frequencies in a radiation-associated thyroid cancer cohort, we investigated a further 68 unpaired post-Chernobyl samples. For G691S, there was considerable deviation from Hardy-Weinberg equilibrium; more detailed analysis showed that this was linked to age at onset of disease. Among younger patients, the distribution of genotypes conformed to Hardy-Weinberg equilibrium; among older patients, we observed marked deviation (p = 0.0072), with significant over-representation of the rare S allele relative to the younger groups (Fisher's exact, p = 0.0233). This suggests that SNPs in the RET oncogene may play a role in sporadic papillary thyroid carcinoma.

Adolescent↗

Cbf1p modulates chromatin structure, transcription and repair at the Saccharomyces cerevisiae MET16 locus.

The presence of damage in the transcribed strand (TS) of active genes and its position in relation to nucleosomes influence nucleotide excision repair (NER) efficiency. We examined chromatin structure, transcription and repair at the MET16 gene of wild-type and cbf1Delta Saccharomyces cerevisiae cells under repressing or derepressing conditions. Cbf1p is a sequence-specific DNA binding protein required for MET16 chromatin remodelling. Irrespective of the level of transcription, repair at the MspI restriction fragment of MET16 exhibits periodicity in line with nucleosome positions in both strands of the regulatory region and the non-transcribed strand of the coding region. However, repair in the coding region of the TS is always faster, but exhibits periodicity only when MET16 is repressed. In general, absence of Cbf1p decreased repair in the sequences examined, although the effects were more dramatic in the Cbf1p remodelled area, with repair being reduced to the lowest levels within the nucleosome cores of this region. Our results indicate that repair at the promoter and coding regions of this lowly transcribed gene are dependent on both chromatin structure and the level of transcription. The data are discussed in light of current models relating NER and chromatin structure.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Serum survival and plasmid possession by strains of Salmonella enteritidis, Salm. typhimurium and Salm. virchow.

Strains of Salmonella enteritidis, Salm. typhimurium and Salm. virchow, carrying different numbers of plasmids, were examined for the ability to multiply in sera. Viable counts were performed to monitor the kinetics of growth of bacteria when in human, chicken and turkey sera. The presence of plasmids in Salm. enteritidis, Salm. typhimurium and Salm. virchow reduced considerably the ability of strains of these serotypes to multiply in serum. SDS-PAGE was used to show that growth of Salm. enteritidis in serum did not involve changes in outer membrane proteins or lipopolysaccharide. It was concluded that the carriage of plasmids may be disadvantageous for the survival in serum of certain common salmonella serotypes.

Animals↗

Correlation of change in phage type with pulsed field profile and 16S rrn profile in Salmonella enteritidis phage types 4, 7 and 9a.

Using pulsed-field gel electrophoresis (PFGE) and 16S rRNA (rrn) analysis (ribotyping), the in vivo derivation of strains of Salmonella enteritidis PTs 9a and 7 from a strain of S. enteritidis PT 4 has been demonstrated. All strains were isolated from a single patient over a 6-week period. Further studies have demonstrated that in terms of pulsed-field profile and ribotype, the genotypes of the patient-derived strains differed from those of the reference strains of the respective phage types. It is concluded that when used in combination, these methods can provide evidence of phylogenetic relationships in apparently unrelated S. enteritidis phage types isolated during pathogenesis of disease.

Bacteriophage Typing↗

Subdivision of Salmonella enteritidis PT 4 by pulsed-field gel electrophoresis: potential for epidemiological surveillance.

Using pulsed-field gel electrophoresis (PFGE), nine profile types were identified in XbaI digests of a panel of strains of Salmonella enteritidis phage type 4 (PT 4) isolated in England and Wales between 1967 and 1992. When applied to 39 isolates from humans, chickens, poultry products and feed, strains belonging to pulsed-field profile (PFP) 1 predominated. DNA-DNA hybridization studies demonstrated that a band of approximately 57 kb was associated with the presence of the 38 MDa S. enteritidis 'serovar-specific' plasmid. It is concluded that PFGE provides a method for discriminating strains of S. enteritidis PT 4 suitable for epidemiological investigations.

Animals↗

Inheritance of microphthalmia with coloboma in the Australian shepherd dog.

Microphthalmia with coloboma behaves as an incompletely penetrant recessive trait in the merle Australian Shepherd dog. Microphthalmia and related anomalies occurred more often in merle dogs with predominate white than in merles with limited white hair coat. The study did not establish a genetic relationship between the amount of merling and microphthalmia. The inheritance of merling behaved as a dominant trait, but fewer non-merles occurred than were expected. Variations in white spotting were satisfactorily explained by several hypotheses involving 2 or 3 alleles at the S locus. Each requires some or all homozygous merles to be largely white and 1 or more of the S alleles to exhibit some extent of dominance over other alleles in the series.

Animals↗