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Biomedical subjects

M Clinton

Publications and source records attributed to M Clinton.

At least 19 recordsLinked to original sources

Dosage compensation in birds.

The Z and W sex chromosomes of birds have evolved independently from the mammalian X and Y chromosomes [1]. Unlike mammals, female birds are heterogametic (ZW), while males are homogametic (ZZ). Therefore male birds, like female mammals, carry a double dose of sex-linked genes relative to the other sex. Other animals with nonhomologous sex chromosomes possess "dosage compensation" systems to equalize the expression of sex-linked genes. Dosage compensation occurs in animals as diverse as mammals, insects, and nematodes, although the mechanisms involved differ profoundly [2]. In birds, however, it is widely accepted that dosage compensation does not occur [3-5], and the differential expression of Z-linked genes has been suggested to underlie the avian sex-determination mechanism [6]. Here we show equivalent expression of at least six of nine Z chromosome genes in male and female chick embryos by using real-time quantitative PCR [7]. Only the Z-linked ScII gene, whose ortholog in Caenorhabditis elegans plays a crucial role in dosage compensation [8], escapes compensation by this assay. Our results imply that the majority of Z-linked genes in the chicken are dosage compensated.

Aconitate Hydratase↗

An overview of factors influencing sex determination and gonadal development in birds.

The morphological development of the embryonic gonads is very similar in birds and mammals, and recent evidence suggests that the genes involved in this process are conserved between these classes of vertebrates. The genetic mechanism by which sex is determined in birds remains to be elucidated, although recent studies have reinforced the contention that steroids may play an important role in the structural development of the testes and ovaries in birds. So far, few genes have been assigned to the avian sex chromosomes, but it is known that the Z and W chromosomes do not share significant homology with the mammalian X and Y chromosomes. The commercial importance of poultry breeding has motivated considerable investment in developing physical and genetic maps of the chicken genome. These efforts, in combination with modern molecular approaches to analyzing gene expression, should help to elucidate the sex-determining mechanism in birds in the near future.

Animals↗

A novel erythroid-specific marker of transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathies (TSE) are a group of invariably fatal neurodegenerative diseases and include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in deer and elk, and Kuru disease, Creutzfeldt-Jakob disease (CJD) and variant CJD in humans. The pathological effects of disease occur predominantly in the CNS (central nervous system), where common hallmarks include vacuolation, gliosis, accumulation of a protease-resistant, abnormally folded isoform of the prion protein (PrPSc) and neuronal cell death. Lack of understanding of the molecular mechanisms underlying disease pathogenesis, particularly in non-CNS tissues, means that there are currently no effective strategies for early diagnosis or therapeutic intervention of TSEs. Here we report the first identification of a molecular marker that is easily detectable in readily accessible tissues. We demonstrate that a dramatic decrease in expression of a transcript specific to erythroid lineage cells is a common feature of TSEs. Our findings indicate a previously unrecognized role for involvement of the erythroid lineage in the etiology of TSE pathogenesis and should provide a new focus for research into diagnostic and therapeutic strategies.

Activins↗

Sexing chick embryos: a rapid and simple protocol.

1. Analysis of gene expression in the developing chick gonads requires the collection of male and female tissues from embryos between 3.5 d and 8.5 d of development. However, male and female chick embryos are indistinguishable by morphological examination before d 7.5 of development. 2. Sex identification of earlier embryos is only possible by molecular methods, which at present are laborious and time consuming. 3. We have devised a PCR-based sexing protocol which combines both sex specific and control reactions in a single tube assay. The assay is rapid and effective over a wide range of DNA concentrations and is tolerant of poor quality DNA. 4. Procedures are described for identifying the sex of individual embryos using either tissue samples or a small number of cells recovered from amniotic fluid.

Amniotic Fluid↗

Differentiation-dependent expression of connective tissue growth factor and lysyl oxidase messenger ribonucleic acids in rat granulosa cells.

Searching for novel genes involved in tissue remodeling during ovarian folliculogenesis, we carried out differential display RT-PCR (DDRT-PCR) on RNA from gonadotropin-stimulated rat granulosa cells (GC). GC from preantral and early antral follicles in immature rat ovaries were cultured in serum-free medium containing no hormone (control), recombinant human FSH (10 ng/ml), 5alpha-dihydrotestosterone (DHT; 10(-6) M), or FSH plus DHT. Total cellular RNA was extracted from cells at 6, 12, 24, and 48 h of treatment for DDRT-PCR analysis, corresponding to an estimated 60% saturation of the messenger RNA (mRNA) population. Six distinct complementary DNA clones were obtained that reproduced the DDRT-PCR profile on a Northern blot of the corresponding RNA samples. Two of these clones detected transcripts that were strongly down-regulated by FSH. One corresponded to connective tissue growth factor (CTGF), a cysteine-rich secreted protein related to platelet-derived growth factor that is implicated in mitogenesis and angiogenesis, and a second was identical to lysyl oxidase (LO), a key participant in extracellular matrix deposition. In detailed expression studies, Northern analysis revealed a single, approximately 2.5-kb CTGF transcript maximally suppressed within 3 h of exposure to FSH with or without DHT and two LO transcripts ( approximately 3.8 and approximately 5.2 kb) maximally suppressed at 6 h. DHT alone did not affect CTGF mRNA, but strongly enhanced LO mRNA relative to the control value. In vivo, CTGF and LO transcripts were significantly suppressed in GC 48 h after equine CG injection (10 IU, ip) compared with untreated controls and were further reduced 12 h after administration of additional 10 IU hCG to induce luteinization. In situ hybridization confirmed GC in preantral/early antral follicles as principal sites of CTGF and LO mRNA expression. We conclude that expression of CTGF and LO mRNAs is inversely related to GC differentiation. The encoded proteins probably have roles in the regulation of tissue remodeling and extracellular matrix formation during early follicular development.

Animals↗

Gene expression changes during murine postnatal brain development.

BACKGROUND: For most vertebrate organs and tissues, the majority of development occurs during embryogenesis, and postnatal changes are primarily concerned with growth. The central nervous system is unusual in that a considerable amount of morphological development, cell differentiation and acquisition of function, takes place during postnatal development. As yet, the molecular mechanisms underlying these complex developmental processes are not well understood. In order to identify markers for these developmental processes, we have analyzed the expression profiles, during postnatal murine brain development, of approximately 25,000 transcripts. This analysis, performed at day 1, day 10, day 20 and day 42 of postnatal development, identified a large number of developmentally regulated genes which we have assigned into three broad expression categories. RESULTS: Expression levels at four timepoints during postnatal murine brain development were established for approximately 25,000 gene transcripts. Approximately 1% of the genes examined displayed a developmentally regulated pattern of expression and we provide all the necessary information required to easily obtain molecular markers for a subset of these developmentally regulated transcripts. Of this subset, 61 showed increasing expression during development, 61 showed decreasing expression during development, and 9 exhibited a peak of expression during this period. CONCLUSIONS: A small percentage of the genes expressed in the postnatal developing brain show changes in expression level during the newborn to adult phase of development. It is likely that these developmentally regulated transcripts represent molecular markers for the complex developmental process occurring in the postnatal brain.

Aging↗

Predicting early adolescent substance use: do risk factors differ depending on age of onset?

This study was designed to identify different risk models associated with non-use, first use, and prior substance use among a group of early adolescents. A total of 582 students completed a self-report questionnaire at the beginning and end of sixth grade. Nine predictor variables were used in discriminant function analysis to classify adolescents into three groups. Five variables distinguished non-users (never used by the end of sixth grade) and new users (first used during sixth grade) from prior users (first used before sixth grade). Prior users were found to have weaker decision making skills, more susceptibility to peer pressure, more negative perceptions of school, less confidence in their skills, and an increased likelihood of being male. A second function indicated that new users were similar to prior users in that they had less positive peer relations, were more likely to come from single parent families, and had less knowledge about alcohol and drugs than did non-users. The similarities and differences between new and prior users have implications for future research and prevention programming.

Adolescent↗

Scoping mental health nursing education.

In late 1999 the National Mental Health Working Group of the Australian Health Ministers Advisory Council commissioned the Australian and New Zealand College of Mental Health Nurses to undertake a scoping study of mental health nursing. A final report will be submitted to the National Mental Health Working Group in February 2000. The purpose of this article is to draw attention to some of the systemic problems that confront the education of mental health nurses in Australia. Shortcomings in the preparation of undergraduate students of nursing for commencing practice in mental health nursing are described and comments are given on issues affecting the quality of postgraduate mental health nursing education.

Australia↗

Scoping the Australian mental health nursing workforce.

This is the second of four articles on the Scoping Study of the Australian mental health nursing workforce conducted on behalf of the Australian and New Zealand College of Mental Health Nurses (ANZCMHN) for the Australian Health Ministers Advisory Council (AHMAC) National Working Group on Mental Health (NWGMH). Its purpose is to focus on overlooked issues in planning the mental health nursing workforce. Whereas it is acknowledged that there are problems in the supply of mental health nurses, it is argued that equal attention needs to be given to addressing the working conditions and rewards of mental health nurses.

Australia↗

Collaborative education and social stereotypes.

The purpose of this paper is to present results from a two-year collaborative education project conducted with people with a serious mental illness and senior undergraduate students of nursing at the Centre for Mental Health Nursing Research at Queensland University of Technology. The study was funded by the Australian Commonwealth Government and was completed in June 1998. The results suggest that collaborative education is an effective means for breaking down social stereotypical thinking about people with a mental illness. A similar finding with respect to the stigmatization of undergraduates supports this hypothesis. Implications for psychiatric rehabilitation and the undergraduate education of students of nursing are explored.

Attitude of Health Personnel↗

"What should I say?": qualitative findings on dilemmas in palliative care nursing.

The nursing literature suggests that talking and listening to patients about issues associated with death and dying, is both important and difficult, and may be improved with training. This discussion presents the results of recent nursing research to confirm, and elaborate on, this theme. In this research participants touched on many central issues in communicating with patients that included articulating a sense of discomfort and inadequacy about the whole process, detailing the innumerable blocks to open communication [e.g., interference, denial, unrealistic optimism, resistance, collusion and anger] and sharing their sense of success and failure. The insights of nurses who participated in this research testify to the ongoing need to prioritize the development of nursing skills and support in this challenging but important area.

Adaptation, Psychological↗

A rapid protocol for the authentication of isolated differential display RT-PCR CDNAs.

The most time-consuming and problematic step in the overall DDRT-PCR technique is the confirmation that the isolated cDNA clone represents a differentially expressed gene. We have previously suggested that the majority of apparent false positives generated by DDRT-PCR do in fact result from the PCR reamplification of cDNA species which co-migrate with the cDNA of interest, and we have outlined a procedure to effectively eliminate these from further study. However, in situations where RNA is limiting, it is still desirable to confirm that a purified cDNA amplicon does, in fact, represent the originally observed differentially expressed gene prior to embarking on expression studies.

Animals↗

Promoting a good death: an agenda for outcomes research--a review of the literature.

Outcomes research is topical in discussions about health-related research. Its emphasis on effectiveness creates an important opportunity for nurse researchers to strengthen the linkages between theory, outcomes research and nursing practice but, before care can be more effective, it is logical to establish patients' desired outcomes. A thorough review of the implications of this requirement for the care of hospice patients is needed, but is lacking in the literature. Therefore, the literature on a 'good death' is reviewed as a step towards assisting hospice patients to achieve what they regard as an acceptable death. The starting point is to define more clearly what it means to die a good death. The relationship between hospice care and achieving a good death is then examined.

Attitude of Health Personnel↗

Mediating conflict and control: practice challenges for nurses working in palliative care.

A work-based professional development program was offered to a group of registered nurses working in palliative care. The goal of the program was to improve skills in psychosocial care (Yates et al., 1996). Participants were encouraged to reflect critically on their practice experience within a group setting. The focus of the group discussion and reflection were shared practice incidents. Each participant was given the opportunity to identify and describe an incident from their professional practice that presented a challenging issue within palliative nursing. This paper explores the themes of conflict and control, evident within the collection of fifteen practice incidents and discusses the nurses' role as mediator. The concepts of patient advocacy and professional autonomy are challenged through the nurses' experience of providing care within a hierarchical and bureaucratic health service. The outcome of reflection for the organization is most effective when shared experience and collective action (rather than individual practice) are the focus.

Adult↗

Perceived social support and community adaptation in schizophrenia.

Prompted by the continuing transition to community care, mental health nurses are considering the role of social support in community adaptation. This article demonstrates the importance of distinguishing between kinds of social support and presents findings from the first round data of a longitudinal study of community adaptation in 156 people with schizophrenia conducted in Brisbane, Australia. All clients were interviewed using the relevant subscales of the Diagnostic Interview Schedule to confirm a primary diagnosis of schizophrenia. The study set out to investigate the relationship between community adaptation and social support. Community adaptation was measured with the Brief Psychiatric Rating Scale (BPRS), the Life Skills Profile (LSP) and measures of dissatisfaction with life and problems in daily living developed by the authors. Social support was measured with the Arizona Social Support Interview Schedule (ASSIS). The BPRS and ASSIS were incorporated into a client interview conducted by trained interviewers. The LSP was completed on each client by an informal carer (parent, relative or friend) or a professional carer (case manager or other health professional) nominated by the client. Hierarchical regression analysis was used to examine the relationship between community adaptation and four sets of social support variables. Given the order in which variables were entered in regression equations, a set of perceived social support variables was found to account for the largest unique variance of four measures of community adaptation in 96 people with schizophrenia for whom complete data are available from the first round of the three-wave longitudinal study. A set of the subjective experiences of the clients accounted for the largest unique variance in measures of symptomatology, life skills, dissatisfaction with life, and problems in daily living. Sets of community support, household support and functional variables accounted for less variance. Implications for mental health nursing practice are considered.

Adaptation, Psychological↗

On reflection in action: unaddressed issues in refocusing the debate on reflective practice.

Reflective practice is now widely debated as a means of improving nursing practice. However, assumptions about reflective practice are rarely clarified and seldom subjected to critique. Therefore, the purpose of this paper is to take up Clarke, James & Kelly's suggestion that limits to the scope and depth of reflection be considered. This is achieved by reflecting on what these authors claim it means to reflect in action. Four arguments are presented: (i) that nurses cannot be conscious of all aspects of nursing practice because there are aspects of practice that cannot be represented in consiousness, (ii) that those aspects of practice that can be represented in consciousness can be so only imperfectly, (iii) that all such representations are not reflexive, and (iv) that any representation in the form of an internal dialogue that could be regarded as reflection is overdetermined. Implications for reflexivity are then considered.

Consciousness↗