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M McKeown

Publications and source records attributed to M McKeown.

At least 19 recordsLinked to original sources
PubMed1996

Understanding the needs of relatives of patients within a special hospital for mentally disordered offenders: a basis for improved services.

This paper outlines one component of a major research study, which will form the basis for a new service for relatives of schizophrenia sufferers within a special hospital. The aim of this initial component has been twofold: firstly to identify and understand the needs of relatives in terms of their present knowledge and understanding of schizophrenia; and secondly to establish what stress the relatives are presently experiencing in maintaining contact with patients and whether this stress may have an impact on the management of schizophrenia at the hospital. A purposive sample of 17 relatives were interviewed using two semi-structured interview protocols. All interviews were audio-taped and later transcribed for analysis. The data have provided an illuminating insight into the thoughts and feelings of relatives and indicate many ways in which a service for relatives could be tailored. It is apparent that many relatives are currently not being supported, involved or allowed to contribute to the care of their family member at Ashworth Hospital. This present situation is stressful for relatives and is likely to have a detrimental effect on the course of schizophrenia in patients at Ashworth Hospital.

Family↗
PubMed1996

att, a target for regulation by tra2 in the testes of Drosophila melanogaster, encodes alternative RNAs and alternative proteins.

We have identified a gene, alternative testis transcripts (att), which is alternatively expressed, at both the RNA and protein levels, in testes and somatic tissues. The testis-specific RNA differs from somatic RNAs in both promoter usage and RNA processing and is dependent on the function of the transformer 2 gene. The differences between the somatic and testis RNAs have substantial consequences at the protein level. The somatic RNAs encode a protein with homology to the mammalian Graves' disease carrier proteins. The testis RNA lacks the initiation codons used in somatic tissue and encodes two different proteins. One of these begins in a testis-specific exon, uses a reading frame different from that for the somatic protein, and is completely novel. The other protein initiates translation in the frame of the somatic RNA at a Len CUG codon which is within the open reading frame for the somatic protein. This produces a novel truncated version of the Graves' disease carrier protein-like protein that lacks all sequences N terminal to the first transmembrane domain.

Alternative Splicing↗
PubMed1995

Identification and characterization of a Drosophila nuclear receptor with the ability to inhibit the ecdysone response.

In a search for retinoid X receptor-like molecules in Drosophila, we have identified an additional member of the nuclear receptor superfamily, XR78E/F. In the DNA-binding domain, XR78E/F is closely related to the mammalian receptor TR2, as well as to the nuclear receptors Coup-TF and Seven-up. We demonstrate that XR78E/F binds as a homodimer to direct repeats of the sequence AGGTCA. In transient transfection assays, XR78E/F represses ecdysone signaling in a DNA-binding-dependent fashion. XR78E/F has its highest expression in third-instar larvae and prepupae. These experiments suggest that XR78E/F may play a regulatory role in the transcriptional cascade triggered by the hormone ecdysone in Drosophila.

Amino Acid Sequence↗
PubMed1995

The transformation of nurses' work?

This paper offers a critical discussion of how current and planned changes in the labour process within the National Health Service (NHS), with particular reference to nursing as an occupational group, are likely to influence the industrial relations aspects of nursing management. An attempt is made to apply concepts developed within the wider sociology of work, to the reality of latter day nurses' experience. In this respect, the question will be addressed: do management approaches to the reorganization of work in health care settings constitute, or herald, an actual 'transformation' of nurses' work? The approach adopted places concern over the introduction of productivity or performance related pay, or the implementation of nursing skill-mix reviews within an analytic context which considers issues of control over working practices. As such, management and unions' responses to NHS Executive calls for increasing reorganization of nurses' work and remuneration structures may be illuminated by an understanding of this issue of control. This would entail a departure from simplistic analyses, focused solely upon narrowly defined efficiency concerns.

Efficiency, Organizational↗
PubMed1995

Clinical management: a special case*.

This paper briefly discusses the development of some of the principles of case management as they have been applied in the community. As a clinical management system we argue that the key elements of case management could and should be applied within institutional settings. We draw as an example Ashworth Special Hospital recently criticized for its lack of co-ordinated care by a Public Inquiry Committee. The resulting discussion focuses upon a rehabilitation framework which could be used to implement case management within such a setting; the implementation of such a framework and the benefits that would be gained.

Hospitals, Special↗
PubMed1995

Staff perception of illicit drug use within a special hospital.

This paper presents the results of a survey of staff perceptions of issues related to illicit drug use amongst patients within a UK Special (forensic) Hospital. The issues examined were: the nature and extent of drug-related problems; current management strategies and their perceived efficacy; suggestions for improved management strategy; and identification of staff training needs. Data were collected utilizing a questionnaire distributed all patient-care team members and representatives of disciplines working in off-ward areas (n = 311). The response rate was approximately 40%. Analysis of the returns suggests that staff concerns are largely focused on issues around the supply of drugs. A significant level of ignorance regarding illicit drugs and their usage was revealed, indicating a need for coordinated training. A review of literature suggests that future management strategies should not be solely directed towards supply restriction. A discussion of the results highlights parallels between Ashworth Hospital staff perceptions of illicit drug problems, media coverage of the same, and the findings of earlier sociological studies of deviance, subculture and moral panic.

Attitude of Health Personnel↗
PubMed1995

Seven-up inhibits ultraspiracle-based signaling pathways in vitro and in vivo.

Seven-up (Svp), the Drosophila homolog of the chicken ovalbumin upstream transcription factor (COUP-TF); Ultraspiracle (Usp), the Drosophila homolog of the retinoid X receptor; and the ecdysone receptor are all members of the nuclear/steroid receptor superfamily. COUP-TF negatively regulates hormonal signaling involving retinoid X receptor in tissue culture systems. Here we demonstrate that Svp, like COUP-TF, can modulate Ultraspiracle-based hormonal signaling both in vitro and in vivo. Transfection assays in CV-1 cells demonstrate that Seven-up can inhibit ecdysone-dependent transactivation by the ecdysone receptor complex, a heterodimeric complex of Usp and ecdysone receptor. This repression depends on the dose of Svp and occurs with two different Drosophila ecdysone response elements. Ectopic expression of Svp in vivo induces lethality during early metamorphosis, the time of maximal ecdysone responsiveness. Concomitant overexpression of Usp rescues the larvae from the lethal effects of Svp. DNA binding studies show that Svp can bind to various direct repeats of the sequence AGGTCA but cannot bind to one of the ecdysone response elements used in the transient transfection assays. Our results suggest that Svp-mediated repression can occur by both DNA binding competition and protein-protein interactions.

Animals↗
PubMed1994

Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx.

We report here the identification of a unique vertebrate nuclear receptor, Tlx, which is expressed exclusively in the neuroepithelium of the embryonic brain. Sequence comparison reveals striking similarity to the product of the Drosophila terminal/gap gene tailless (tll), which is expressed in the embryonic brain and is required for brain development in flies. In vitro DNA-binding assays demonstrated that Tlx and Tll proteins share a target gene specificity that is unique among the nuclear receptor superfamily. Ectopic expression of Tlx in fly embryos caused a repression of segmentation comparable to that elicited by Tll. The similarities in structure, expression pattern, target gene specificity and phenotypes in transgenic flies suggest conservation of genetic programs upstream and downstream of this Tlx/Tll class of nuclear receptors during embryogenesis.

Amino Acid Sequence↗
PubMed1994

Multiple portions of a small region of the Drosophila transformer gene are required for efficient in vivo sex-specific regulated RNA splicing and in vitro sex-lethal binding.

The transformer gene of Drosophila is regulated by Sex-lethal-dependent 3' splice site blockage. 40 nucleotides immediately upstream of the regulated splice site are sufficient to direct sex-specific regulated splicing in transgenic animals. This entire region appears to be necessary for regulation and for efficient Sex-lethal binding. Natural splice sites containing partial homology to transformer do not show regulation. Mutations which replace the 16 nucleotides surrounding the branch point or alter single nucleotides near the splice site eliminate or reduce regulation without eliminating splicing. Mutations which reduce or eliminate regulation in vivo reduce binding to Sex-lethal in vitro, consistent with the hypothesis that these mutations bring about their effects by altering Sex-lethal binding rather than by altering binding sites for additional non-Sex-lethal factors.

Animals↗
PubMed1993

Functional ecdysone receptor is the product of EcR and Ultraspiracle genes.

Although the biological activity of the insect moulting hormone ecdysone, is manifested through a hormonally regulated transcriptional cascade associated with chromosomal puffing, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor (EcR) is by itself incapable of high-affinity DNA binding or transcriptional activation. Rather, these activities are dependent on heterodimer formation with Ultraspiracle (USP) the insect homologue of vertebrate retinoid X receptor. Here we report that native EcR and USP are co-localized on ecdysone-responsive loci of polytene chromosomes. Moreover, we show that natural ecdysones selectively promote physical association between EcR and USP, and conversely, that high-affinity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties. These results redefine the ecdysone receptor as a dynamic complex whose activity may be altered by combinatorial interactions among subunits and ligand.

Animals↗
PubMed1993

The role of small nuclear RNAs in RNA splicing.

Recent genetic and biochemical experiments have revealed an intimate and dynamic role for small nuclear RNAs (snRNAs) in multiple steps of RNA-splicing reactions. Both snRNA-substrate and snRNA-snRNA interactions are involved. These interactions concern not only splice site and branch point definition, but also the catalytic reactions of the first and second steps of splicing. Studies reveal a striking conservation between snRNA interactions and interactions found in RNAs encoded by genes with group II self-splicing introns.

Animals↗
PubMed1992

Drosophila ultraspiracle modulates ecdysone receptor function via heterodimer formation.

The vertebrate retinoid X receptor (RXR) has been implicated in the regulation of multiple hormonal signaling pathways through the formation of heteromeric receptor complexes that bind DNA with high affinity. We now demonstrate that ultraspiracle (usp), a Drosophila RXR homolog, can substitute for RXR in stimulating the DNA binding of receptors for retinoic acid, T3, vitamin D, and peroxisome proliferator activators. These observations led to the search and ultimate identification of the ecdysone receptor (EcR) as a Drosophila partner of usp. Together, usp and EcR bind DNA in a highly cooperative fashion. Cotransfection of both EcR and usp expression vectors is required to render cultured mammalian cells ecdysone responsive. These results implicate usp as an integral component of the functional EcR. By demonstrating that receptor heterodimer formation precedes the divergence of vertebrate and invertebrate lineages, these data underscore a central role for RXR and its homolog usp in the evolution and control of the nuclear receptor-based endocrine system.

Animals↗
PubMed1992

The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development.

In Drosophila melanogaster, an increasing number of members of the steroid hormone receptor superfamily are being identified and characterized. Molecular and genetic analysis of receptor function provides evidence for a set of functions underlying the determination of pattern formation, metamorphosis, eye development, and reproduction. Many of the Drosophila receptor genes show striking homologies to mammalian receptor genes. This suggests that genetic analysis in flies could facilitate the generation of biological models that pertain to complex hormonal responses in development and which are relevant to both vertebrate and invertebrate systems.

Animals↗
PubMed1992

Sex differentiation: the role of alternative splicing.

Sex differentiation in Drosophila is controlled by a regulatory cascade with at least three regulated alternative RNA-processing events. The results of recent work have verified much of the earlier molecular and genetic work in this field and have provided a demonstration that both positive and negative regulatory mechanisms are involved.

Animals↗