19 research outputs found

    Analysis of p53 status in tonsillar carcinomas associated with human papillomavirus

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    Tonsillar squamous cell carcinomas (a total of 14) were examined both for the presence of human papillomavirus (HPV) DNA and for p53 alterations. General primer-mediated HPV polymerase chain reaction (GP-PCR) revealed the presence of HPV DNA in 12/14 cases. Subsequent typing by HPV type-specific PCR and sequence or hybridization analysis of GP-PCR products revealed DNA from HPV 16 in seven cases, from HPV 33 in two cases, and from HPV 7, HPV 16/33 and HPV 33/59 each in a single case. p53 immunohistochemistry performed on nine HPV containing tonsillar carcinomas using polyclonal serum CM-1 showed elevated p53 levels in four cases. These included 3/5 HPV 16 containing carcinomas and the HPV 33/59 containing carcinoma. Analysis of p53 mutations using denaturing gradient gel electrophoresis (DGGE) of GC-clamped PCR products of exons 5 to 8 showed p53 gene alterations in 3/13 cases, incuding 2/11 HPV positive cases and 1/2 HPV negative cases. The alterations included a silent point mutation within exon 8 of an HPV 16 containing carcinoma, a 1 bp deletion within exon 8 of an HPV 33 containing carcinoma, and a missense mutation within exon 7 of one of the HPV negative carcinomas. There was evident discrepancy between p53 immunohistochemistry and gene analysis. Four HPV containing cases showing elevated p53 levels did not reveal the presence of exon 5 to 8 alterations affecting the amino acid code, suggesting the presence of mutations occurring in other exons or non-mutational p53 stabilization. The data indicate that HPV and elevated p53 can coexist in tonsillar carcinomas and that despite the low frequency of p53 mutations the presence of HPV is not exclusively related to the absence of mutated p53

    Development of complex executive function over childhood: Longitudinal growth curve modeling of performance on the Groton Maze Learning Task

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    This longitudinal study modeled children's complex executive function (EF) development using the Groton Maze Learning Task (GMLT). Using a cohort-sequential design, 147 children (61 males, 5.5-11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. Race/ethnicity data were not available. Children were assessed on the GMLT at 6-month intervals over 2-years between 2010 and 2012. Growth curve models describe age-related change from 5.5 to 12.5 years old. Results showed a quadratic growth trajectory on each measure of error - that is, those that reflect visuospatial memory, executive control (or the ability to apply rules for action), and complex EF. The ability to apply rules for action, while a rate-limiting factor in complex EF, develops rapidly over early-to-mid childhood

    The association between viral load and concurrent human papillomavirus infection at the genital and anal sites of young women and the impact of vaccination

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    Concurrent genital-anal human papillomavirus (HPV) infections may impose an increased anal cancer risk in women with HPV-related genital lesions. High viral load may facilitate genital-anal HPV concurrence. Genital and anal HPV is reduced by a bivalent HPV16/18 vaccine, yet the effect on concurrent genital-anal HPV remains unclear. This study analyzed viral load in concurrent genital-anal HPV infections, relative to genital-only and anal-only HPV infections and the impact of vaccination in young women. We included 1074 women, who provided both genital and anal swabs. HPV detection and genotyping was performed using the SPF10-DEIA-LiPA25. HPV copy numbers were measured with type-specific qPCRs and corrected for cellular content to obtain the viral load. Concurrent genital-anal HPV often had significantly higher genital viral load (0.09-371 c/cell) than genital-only HPV (3.17E-04-15.9 c/cell, p < 0.0001 to p < 0.05). Moreover, nearly all concurrent genital-anal HPV types had higher genital copy numbers per PCR reaction (157-416E04 c/rxn) than anal copy numbers (0.90-884E01 c/rxn, p < 0.0001 to p < 0.001). Vaccinated women had significantly less infections with HPV16/18 vaccine-types (2.8% vs 13.7%, p < 0.0001) and HPV31/35/45 cross-protective types (7.4% vs 21.1%, p < 0.0001) than unvaccinated women. In conclusion, particularly high genital viral load is found in concurrent genital-anal HPV infections, which are effectively reduced by vaccination
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