Biomedical subjects
Publications and source records attributed to S Pattison.
Many NHS staff feel that they are unable to put their values into action because of the constraints on the service. They want a working environment where trust is possible and mistakes can be made without retribution. The reality is often bullying and attempts at innovation being met with reproach.
This paper attempts a partial, critical look at the construction and use of case studies in ethics education. It argues that the authors and users of case studies are often insufficiently aware of the literary nature of these artefacts: this may lead to some confusion between fiction and reality. Issues of the nature of the genre, the fictional, story-constructing aspect of case studies, the nature of authorship, and the purposes and uses of case studies as "texts" are outlined and discussed. The paper concludes with some critical questions that can be applied to the construction and use of case studies in the light of the foregoing analysis.
Following more than a decade of change, the NHS is keen to explore the values driving its daily life. Consistency between values and behaviour are an important part of building an organisation's identity and confidence. It is likely that pluralistic values inform the NHS more now than was the case in the early years of the welfare state.
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We have reported previously that a 636-bp fragment spanning the 5' two-thirds of the human papillomavirus type 6 (HPV6)-W50 long control region (LCR) functions as a transcriptional silencer (A. Farr, S. Pattison, B.-S. Youn, and A. Roman, J. Gen. Virol. 76:827-835, 1995). We have utilized nested deletion analyses to implicate a 66-bp sequence which appears to be critical for this activity. A comparison of the transcriptional regulatory activities of the LCRs of HPV6-W50 and HPV6b (which has a 94-bp deletion, resulting in the elimination of the 66-bp sequence) indicates that sequences within the 94-bp region negatively regulate the activity of the intact HPV6 LCR. Two sequence-specific DNA-protein interactions were visualized via electrophoretic mobility shift assays. One of the binding events is mediated by the transcriptional repressor CCAAT displacement protein (CDP), a factor which is active in undifferentiated cells but inactive in terminally differentiated cells. This conclusion is based on the following three lines of evidence: (i) a consensus CDP binding site oligonucleotide serves as a competitor in band shift assays, (ii) the band shift complex is not seen when a CDP-negative nuclear extract is used, and (iii) anti-CDP antiserum specifically inhibits the binding. These studies identify a DNA-protein interaction occurring within the 5' end of the LCR which may be important in maintaining the tight link between keratinocyte differentiation and HPV gene expression.
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Human papillomavirus type 6 (HPV-6) DNA is the predominant HPV type found in condyloma acuminata: it is rarely found in carcinomas. We have previously reported cloning and characterizing an HPV-6 from a vulvar condyloma (HPV6-W50) and an HPV-6 from a vulvar carcinoma (HPV6-T70). The E5, E6 and E7 proteins encoded by the two genomes were identical, however, the two genomes differed in the long control region (LCR). Cloning of the entire LCR into the enhancerless plasmid pSVEcat showed that the two LCRs had comparable enhancer activity. Since the major differences between the two LCRs resided in the 5' end of the LCR, upstream of the L1 polyadenylation signal, we subcloned the two LCRs to analyse more closely their effect on cat gene expression. The data indicated that LCR subclones of the two genomes had comparable chloramphenicol acetyltransferase (CAT) activity. A negative regulatory region was detectable when the test plasmids were transfected into HeLa and C33A cells and in primary keratinocytes. A decrease in CAT activity was also detected when the SV40 early promoter was replaced with the putative HPV-6 E6 promoter. The negative regulatory region functioned in a position- and orientation-independent manner, thus fulfilling the definition of a silencer.
This paper describes an initiative in distance learning for cancer prevention for health care professionals throughout the EC. 'Reducing the Risk of Cancers' is a multi-media integrated study pack of learning materials prepared by the Open University (U.K.) with funding from the Europe Against Cancer programme of the European Commission. The teaching materials aim to enhance cancer prevention and health promotion skills and competencies amongst health care professionals at local level. In the paper the background to the pack is considered, the production process is described and the aims and philosophy of the teaching materials are outlined. The content of the pack is described and usage, dissemination and evaluation for health professionals throughout Europe are discussed.
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Scant consideration has been given to the ethical implications of the policy of closing down psychiatric hospitals in favour of community care. The recent adherents of this policy in government have been enthusiastic in encouraging its implementation. This paper has three sections: a brief resumé of the history and principles of community care for the mentally ill; a discussion on the merits and de-merits of psychiatric care in the hospital and in the community; and an outline of some preliminary categories for ethical analysis.
The effect of a class of ligands on the catalytic activity of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) from Torpedo californica electroplax tissue has been studied via the transient reaction of a fluorophoric acetylcholine analog, 7-(N,N-dimethyl)carbamoxy-N-methylquinolinium iodide (M7C). These "peripheral" ligands inhibit the formation of a metastable carbamyl-enzyme intermediate from M7C. They induce slow isomerization to a new conformational state that shows little or no reaction with M7C. At saturating ligand concentration, the unimolecular isomerization rate constant is 0.03 +/- 0.01 sec-1, a slow rate compared to the rate of carbamylation of the active conformation. Peripheral ligands alter the distribution between reactive and unreactive conformations, thus inducing biphasic rates and amplitudes of carbamylation. The amplitudes, but not the two specific rates, are affected by the concentration of ligand. Zn2+ and d-tubocurarine are two ligands that induce the same slow isomerization rate. On the basis of this identity of function by ligands of disparate structure, we postulate the existence of only a single active conformation and a single inactive conformation (stabilized by interaction with both ligands). In the absence of ligands, the active conformation predominates. Peripheral ligands bind specifically to the inactive conformation. Alkaline earth cations such as Ca2+ and Mg2+ interact strongly and preferentially with the active conformation and drive the conformational equilibrium toward the active state. Ligand-induced inactivation is observed both with highly purified trypsin-solubilized enzyme and with enzyme bound to unfractionated membrane fragments.
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