Biomedical subjects

K Purdie

Publications and source records attributed to K Purdie.

4 recordsLinked to original sources

PubMed2005

Does human papillomavirus play a role in the development of bladder transitional cell carcinoma? A comparison of PCR and immunohistochemical analysis.

AIM: To investigate the role of human papillomavirus (HPV) in the development of bladder transitional cell carcinoma (TCC). METHODS: Seventy eight paraffin wax embedded TCC samples were tested for the presence of HPV by two methods. First, immunohistochemistry was carried out using a polyclonal antibody capable of detecting the capsid protein of all known papillomaviruses. The second method was a consensus GP5+/6+ primer mediated polymerase chain reaction (PCR) technique, with the products analysed by both agarose gel electrophoresis and an enzyme immunoassay using type specific oligonucleotide probes for 10 different mucosal genotypes. To exclude false negative results because of the poor quality of DNA extracted from paraffin wax embedded samples, the series was extended to include 20 further blocks for which the corresponding snap frozen unfixed tissue was available. RESULTS: The two methods produced contrasting results, with 47 of the 78 samples positive for HPV antigen and none positive for HPV DNA. HPV DNA was not detected in the 20 additional paraffin wax embedded TCCs or in the 20 paired unfixed samples. In contrast, HPV DNA was amplified by PCR from all six of the paraffin wax embedded cervical carcinoma and anogenital wart control samples. CONCLUSION: The disparity between the two sets of results is probably caused by false positives resulting from the non-specificity of the polyclonal antibody used for immunohistochemistry. These results suggest that HPV is unlikely to play an aetiological role in the development of bladder TCC.

Adult↗

PubMed1997

Cell-type-specific separate regulation of the E6 and E7 promoters of human papillomavirus type 6a by the viral transcription factor E2.

Gene expression of human papillomaviruses (HPV) is tightly controlled by cellular factors and by the virally encoded E2 protein through binding to distinct sites within the regulatory noncoding region. While for the high-risk genital papillomaviruses a single promoter drives the expression of all early genes, a second promoter present in the E6 open reading frame of the low-risk HPV type 6 (HPV6) would allow an independent regulation of E6 and E7 oncogene expression. In this report, we provide the first evidence that E2 regulates both early promoters of HPV6 separately and we show that promoter usage as well as E2 regulation is cell type dependent. Among the different epithelial cell lines tested, only RTS3b cells allowed an expression pattern similar to that observed in naturally infected benign condylomas. While the E6 promoter was repressed by E2 to 50% of its basal activity, the E7 promoter was simultaneously stimulated up to fivefold. Activation of the E7 promoter was mediated predominantly by the binding of E2 to the most promoter-distal E2 binding site. Repression of the E6 promoter depended on the presence of two intact promoter-proximal binding sites. Mutation of both of these repressor binding sites reversed the effect of E2 on the E6 promoter from repression to activation. In contrast, in HT3 cells we observed an E2-mediated activation of the E6 promoter in the context of the wild-type noncoding region. This indicated that repression of the E6 promoter by binding of E2 to both promoter-proximal binding sites did not function in the cellular environment provided by HT3 cells. These data suggest that the separate regulation of the E6 and E7 promoters of HPV6 is mediated through successive occupation of binding sites with different affinities for E2 depending on the intracellular concentration of E2 and on the cellular environment provided by the infected cell.

Animals↗

PubMed1997

A novel human papillomavirus identified in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare inherited condition in which there is widespread infection with human papillomavirus (HPV). Patients have a high risk of developing squamous cell carcinoma and Bowen's disease on sun-exposed sites. We describe a Jamaican man with the typical clinical and histopathological features of EV.HPV 8, 24 and a subtype of HPV 38, along with a novel HPV sequence most closely related to HPV 9 have been detected in his skin lesions. Although skin tumours are rare in black patients with EV and he has lived in a temperate climate most of his life, several of the lesions showed bowenoid atypia and he is at risk of developing invasive cutaneous malignancies.

Epidermodysplasia Verruciformis↗

PubMed1994

Managing meningitis.

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Anti-Bacterial Agents↗