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Biomedical subjects

M Peake

Publications and source records attributed to M Peake.

5 recordsLinked to original sources

An ecdysteroid-responsive gene in a lobster - a potential crustacean member of the steroid hormone receptor superfamily.

The role of ecdysteroids in modulating exoskeletal growth during the moult cycle of Crustacea has been well described. However, little is known about the action of ecdysteroids at the level of gene transcription and regulation in Crustacea. This paper reports the cloning of an ecdysteroid responsive gene, HHR3, a potential Manduca sexta MHR3 homologue in the American lobster, Homarus americanus. Levels of HHR3 expression are up-regulated in response to in vivo injections of premoult concentrations (10(-6) M) of 20-hydroxyecdysone in the epidermal and muscle tissue of the lobster after 6 h. Maximal mRNA levels are observed after 21 h before returning to basal levels. In muscle tissue, elevated levels of HHR3 mRNA follow a time course similar to elevated actin mRNA expression in response to hormonal injection. In contrast, in eyestalk tissue, the HHR3 levels decline up to 21 h post-injection before rising to basal levels after 48 h. Eyestalk, epidermal and leg muscle tissue was extracted over the moult cycle to determine the levels of expression. In muscle, HHR3 is high during the premoult period that corresponds to the period of the moult cycle when the ecdysteroid titre is high. In the epidermis, HHR3 levels are also high during the premoult with elevated levels maintained into the postmoult period. In the eyestalk, mRNA levels of HHR3 show an opposite pattern of expression with low levels during premoult and postmoult and high levels found during the intermoult period. Our results provide novel evidence for an ecdysteroid responsive gene in a crustacean that has many similarities to MHR3 in Manduca and DHR3 in Drosophila melanogaster. This raises the question of whether a similar cascade of ecdysteroid responsive genes exist in other members of Arthropoda such as the Crustacea, as has been demonstrated in Drosophila. In addition, we provide further evidence for negative feedback regulation of ecdysteroids at the site of moult-inhibiting hormone (MIH) production in the lobster eyestalk.

Amino Acid Sequence

Clinical and histologic features of vulvar carcinomas analyzed for human papillomavirus status: evidence that squamous cell carcinoma of the vulva has more than one etiology.

The association between the human papillomavirus (HPV) and malignant neoplasms of the uterine cervix is well established; however, its role in the pathogenesis of vulvar cancer has not been well defined. This study correlates the clinical and histopathologic features of 21 invasive carcinomas of the vulva with the presence of HPV DNA as detected by Southern blot and polymerase chain reaction (PCR) analysis. By one or both techniques, HPV DNA was detected in 10 of the 21 tumors analyzed; all HPVs containing tumors hybridized with HPV-16 probes, although PCR also detected HPV-6 in two of the HPV-16-containing tumors. No HPV-18 DNA was detected in any tumor by PCR or Southern blot hybridization. Both the invasive cancer and the surrounding intraepithelial disease tended to display histopathologic features that usually could distinguish HPV-associated cancers from those without HPV DNA. The intraepithelial lesions associated with HPV-containing tumors were of the bowenoid type with koilocytosis, while tumors lacking HPV generally demonstrated a simplex type of intraepithelial lesion. Invasive tumors with no viral DNA were more frequently keratinizing than the HPV-containing cancers. Race, parity, hormonal therapy, and alcohol use did not affect the HPV status; however, HPV DNA was more prevalent in the tumors of younger women and in those with a history of tobacco use. Human papillomavirus status had no impact on the stage of disease or its prognosis. These findings identify two subsets of vulvar carcinoma cases based on HPV hybridization data and the histopathologic characteristics of the tumor.

Adult

Multi-centre clinical respiratory research: a new approach?

BACKGROUND: Recruitment to clinical trials organised by the research committee of the British Thoracic Society (BTS) has declined. We suspected that this was due to increasing workloads for consultant physicians in the National Health Service (NHS). We investigated possible causes in study 1 and a possible solution in study 2. METHODS: Study 1--a questionnaire was sent to BTS members listing possible factors that might deter them from entering patients into trials. These were scored on a 0-5 scale. Study 2--we set up 13 panels of experts to cover all major fields of respiratory medicine. They were asked to design projects that would address the most important research questions that could be answered by multi-centre clinical trials. We sent 11 projects for scoring to consultant members of the BTS who were asked to score them on scientific merit and on their ability to contribute patients to the study. RESULTS: Study 1--of the 59% of consultants who responded, 77% said that competition with increasing demands on their time was the major reason for not participating. Study 2--40% of consultants returned project scores. Three projects were subsequently selected for grant application. CONCLUSIONS: Clinical research in the UK is under threat from increasing workloads on consultants. One solution to this problem is a national approach to commission major projects. The most important clinical research questions might then still be answered in the limited time available to consultants.

Attitude of Health Personnel