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Biomedical subjects

Michael Clinton

Publications and source records attributed to Michael Clinton.

17 recordsLinked to original sources
PubMed2006

Identification of disease markers by differential display: prion disease.

In order to identify molecular markers of prion disease in peripheral tissues, we used the differential display reverse-transcriptase polymerase chain reaction (DDRT-PCR) procedure to compare gene expression in spleens of infected and uninfected mice. In this study, we identified a novel erythroid-specific gene that was differentially expressed as a result of prion infection. We were able to demonstrate that a decrease in the expression levels of this transcript in hematopoietic tissues was a common feature of prion diseases. Our findings suggest a previously unknown role for the blood erythroid lineage in the development of prion diseases and should provide a new focus for research into diagnostic and therapeutic strategies.

Animals↗
PubMed2005

Placental abnormalities associated with post-natal mortality in sheep somatic cell clones.

We report on cloning experiments designed to explore the causes of peri- and post-natal mortality of cloned lambs. A total of 93 blastocysts obtained by nuclear transfer of somatic cells (granulosa cells) were transferred into 41 recipient ewes, and pregnancies were monitored by ultrasound scanning. In vitro derived, fertilized embryos (IVF, n=123) were also transferred to assess oocyte competence, and naturally mated ewes (n=120) were analysed as well. Cloned embryos developed to the blastocyst stage and implanted at the same rate as IVF embryos. After day 30 of gestation, however, dramatic losses occurred, and only 12 out of 93 (13%) clones reached full-term development, compared to 51 out of 123 (41.6%) lambs born from the IVF control embryos. Three full-term lamb clones were delivered stillborn, as a result of placental degeneration. A further five clone recipients developed hydroallantois. Their lambs died within 24h following delivery by caesarian section, and displayed degenerative lesions in liver and kidney resulting from the severe hydroallantois. One set of twins was delivered by assisted parturition at day 150, but died 24h later due to respiratory distress syndrome. The remaining two clone recipients underwent caesarian section, and the corresponding two lambs displayed signs of respiratory dysfunction and died at approximately 1 month of age due to a bacterial complication. Blood samples collected from the cloned lambs after birth revealed a wide range of abnormalities indicative of kidney and liver dysfunction. Macroscopical and histopathological examination of the placentae revealed a marked reduction in vascularization, particularly at the apex of the villous processes, as well as a loss of differentiation of the trophoblastic epithelium. Our results strongly suggest that post-mortality in cloned lambs is mainly caused by placental abnormalities.

Animals↗
PubMed2005

Assessing competency in nursing: a comparison of nurses prepared through degree and diploma programmes.

AIMS AND OBJECTIVES: The present study aimed to investigate the competencies of qualifiers from three-year degree and three-year diploma courses in England at one, two and three years after qualification. BACKGROUND: The provision of three-year preregistration nursing degrees in the UK has increased in recent years and in many colleges degrees are offered alongside the existing three-year diploma courses. Yet little is known about the relationship between these different education programmes and the competence of qualifiers. METHODS: A cross-sectional survey design was employed to make comparisons of both self-reported and line-manager-rated competencies of graduate and diplomate nurses who had qualified up to three years previously. INSTRUMENTS: A revised version of the Nursing Competencies Questionnaire was used to measure both overall competence and also eight specific nursing competencies. A shortened version of this scale was also used to assess internal consistency across measures. Two additional competencies, research awareness and policy awareness, were also measured. RESULTS: Structural equation modelling found very little difference in the overall competence and specific competencies of graduates and diplomates. Where differences were found in the self-report data, diplomates scored more highly than graduates in the constructs of planning and social participation; however, these differences became non-significant when background variables were controlled for. LIMITATIONS: The findings are interpreted with caution due to the size of differences, the size of some of the samples of respondents and the developmental stage of the instrument used. CONCLUSIONS: It does not appear that graduates and diplomates in England differ in their level of competence to any great extent as measured by the Nursing Competencies Questionnaire. Areas of further work are discussed in the light of the findings. RELEVANCE TO CLINICAL PRACTICE: While this may alleviate concerns about clinical disparities between the two groups, it raises questions about the proposed benefits to nursing of three-year preregistration degrees in terms of quality of care during the first three years of qualification.

Adult↗
PubMed2005

Job satisfaction in nursing: validation of a new instrument for the UK.

AIM: To develop a new, valid and reliable instrument that has been designed and evaluated to measure job satisfaction as perceived by nurses with specific aspects of contemporary nursing. BACKGROUND: Job satisfaction is a key concept within workforce research in nursing and is particularly important within the present climate in the UK due to findings linking satisfaction with both quality of care and retention of nurses. METHOD(S): Exploratory and confirmatory factor analyses were carried out on a large longitudinal dataset from a study of Adult-branch diploma-qualified nurses in England who completed the scale at three time-points after qualification. RESULTS: A six-factor solution was supported and replicated in a further sample of recently qualified graduate nurses. The instrument was also acceptably reliable. CONCLUSION: This new instrument is a concise, highly practical and flexible tool, which can be used in a range of health care settings and in different measurement contexts.

Attitude of Health Personnel↗
PubMed2004

Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways.

Obesity-related diseases are poised to become the primary cause of death in developed nations. While a number of monogenic causes of obesity have recently been identified, these are responsible for only a small proportion of human cases of obesity. Quantitative trait locus (QTL) studies using animal models have revealed hundreds of potential loci that affect obesity; however, few have been further analyzed beyond the original QTL scan. We previously mapped four QTL in an F(2) between divergently selected Fat (F) and Lean (L) lines. A QTL of large effect on chromosome 15 (Fob3) was subsequently mapped to a higher resolution into two smaller-effect QTL (Fob3a and Fob3b) using crosses between the F-line and a congenic line containing L-line alleles at the Fob3 QTL region. Here we report the gene expression characterization of Fob3b. Microarray expression analysis using the NIA-NIH 15K cDNA array set containing 14,938 mouse ESTs was employed to identify candidate genes and pathways that are differentially expressed between the F-line and a congenic line containing only the Fob3b QTL (Fob3b-line). Our study suggests squalene epoxidase (Sqle), a cholesterol biosynthesis enzyme, as a strong positional candidate gene for Fob3b. Several other cholesterol biosynthesis pathway genes unlinked to Fob3b were found to be differentially expressed, suggesting that a perturbation of this pathway could be in part responsible for the phenotypic difference between the F-line and Fob3b-line mice.

Animals↗
PubMed2004

Gonadotropin-releasing hormone regulates expression of the DNA damage repair gene, Fanconi anemia A, in pituitary gonadotroph cells.

Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse L beta T2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of L beta T2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature alpha T3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA.

Animals↗
PubMed2004

Genetic complexity of an obesity QTL ( Fob3) revealed by detailed genetic mapping.

Obesity is proving to be a serious health concern in the developed world as well as an unwanted component of growth in livestock production. While recent advances in genetics have identified a number of monogenic causes of obesity, these are responsible for only a small proportion of human cases of obesity. By divergent selection for high and low fat content over 60 generations, we have created Fat (F) and Lean (L) lines of mice that represent a model of polygenic obesity similar to the situation in human populations. From previous crosses of these lines, four body fat quantitative trait loci (QTL) were identified. We have created congenic lines (F(chr15L)), by recurrent marker-assisted backcrossing, to introgress the QTL region with the highest LOD score, Fob3 on Chr 15, from the L-Iine into the F-line background. We have further mapped this QTL by progeny testing of recombinants, produced from crosses between the F-line and congenic F(chrl5L) mice, showing that the Fob3 QTL region is a composite of at least two smaller effect QTL-the proximal QTL Fob3a is a late-onset obesity QTL, whereas the distal Fob3b is an early-onset obesity QTL.

Analysis of Variance↗
PubMed2004

Creating diversity in the healthcare workforce. The role of pre-registration nurse education in the UK.

It has been suggested that the introduction of first the diploma pre-registration course and then the three-year degree pre-registration course are likely to have an impact upon the diversity of the future nursing workforce in the UK. Using findings from three large-scale projects, this paper assesses the nature of these changes by comparing the diversity within recently qualified cohorts of graduate, diplomate and certificate-qualified nurses. Findings indicate little difference between the three groups in terms of gender and ethnic origin. A higher proportion of graduates had academic qualifications, which were generally higher than the qualifications held by the other groups of nurses. However, diplomates were the most diverse group overall, being older and more likely to have children, and also having greater previous working experiences. The overall conclusion is that, despite qualification differences, the level of diversity amongst degree-qualifiers was a return to the lower levels associated with qualifiers from certificate courses. Thus the introduction of degree courses may dilute the relative success of the diploma course in terms of the recruitment of a more diverse workforce. The findings are considered in the context of current debates about the future shape of nurse education in the UK.

Adult↗
PubMed2004

Stroke care in the home: the impact of social support on the general health of family caregivers.

BACKGROUND: Throughout the stroke rehabilitation process, community care is one of the most important elements. Learning to live with and take care of a family member with a stroke is immensely complex and demanding. Without appropriate support, family caregivers are at risk of their own general health decreasing, thus becoming a patient themselves - the second patient in the family. AIM: The aim of this study was to examine aspects of social support available to family caregivers during the first 12-week transitional period following hospital discharge. DESIGN AND METHOD: This study adopted a cross-sectional descriptive design. Regression analysis was performed for examining the types of social support received and the general health of family caregivers. Open-ended questions were used to gain a better understanding of situation-specific supports including their availability, utilization and eventual satisfaction. RESULTS: Findings confirm that home care for the stroke survivor is heavy and demanding. Health-related care tasks were the most stressful. Around 40% of the family caregivers reported somatic symptoms. Fewer persons in the social network of the family caregivers had provided support compared with the number of support people that caregivers thought available. Two inadequate types of support were tangible support and information support. Professional advice and feedback in relation to home care skills were particularly lacking. CONCLUSION: Findings of this study affirmed that stroke care needs exceed the hospital boundary. Professional support to family caregivers is essential so as to sustain home care and protect the caregiver's health. This is particular important during the first 12 weeks transitional period after hospital discharge. RELEVANCE TO CLINICAL PRACTICE. This study highlighted the implications of social support to nursing practice, especially in predischarge planning and community care. Findings of this study may provide information and data for service planning and community resources co-ordination to support community stroke care.

Adult↗
PubMed2002

Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts.

Telomere shortening and lack of telomerase activity have been implicated in cellular senescence in human fibroblasts. Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. However, telomere length is not maintained in all cell lines, even though in vitro telomerase activity is restored in all of them. Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability. By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length. The shorter telomere lengths and the extent of karyotypic abnormalities are both functions of hTERT expression level. We conclude that telomerase activity is required to bypass senescence but is not sufficient to prevent telomere erosion and genomic instability at lower levels of expression.

Animals↗
PubMed2002

Ablation of cellular prion protein expression affects mitochondrial numbers and morphology.

The cellular prion protein (PrP(C)), predominantly expressed in the central nervous system, is required for pathogenesis of prion neurodegenerative diseases and its conversion into a pathogenic isoform (PrP(Sc)) is a common feature of disease. While the physiological function of PrP(C) remains unclear, accumulating evidence indicates a role for PrP(C) in oxidative homeostasis in vivo and suggests that PrP(C) may be involved in the cellular response to oxidative stress. Mice in which PrP(C) expression has been ablated are viable and develop normally. Here we show that in an inbred line of mice, in tissues that normally express PrP at moderate to high levels, ablation of PrP(C) results in reduced mitochondrial numbers, unusual mitochondrial morphology, and elevated levels of mitochondrial manganese-dependent superoxide dismutase antioxidant enzyme. These observations may have relevance to the pathogenic mechanism for this group of fatal neurodegenerative conditions.

Amyloid↗
PubMed2002

Towards a Foucauldian reading of the Australian mental health nursing workforce.

This article reflects on the findings of the recently published Scoping Study of the Australian Mental Health Nursing Workforce from the perspective of Foucault's work on 'governmentality'. First, the policy background to the scoping study is described. This is followed by a discussion of Foucauldian concepts and method that will be used to explore selected aspects of the scoping study. The related concepts of 'governmentality' and 'technologies of the self' are used to begin a theoretically grounded analysis of mental health nursing education and practice, with particular attention to discourses of 'change' and 'survival'. The examples chosen are used to support the argument that competing discourses order multiple 'readings' of Australian mental health nursing, including whether or not it is thriving or surviving. The article ends with comments on whether a Foucauldian analysis adds anything to what has been reported in the scoping study.

Attitude of Health Personnel↗
PubMed2002

Improving delivery and offspring viability of in vitro-produced and cloned sheep embryos.

Recently developed, assisted reproductive technologies (e.g., in vitro embryo production and nuclear transfer) have encountered perinatal morbidity/mortality of the offspring produced, which are likely to hinder the application of these techniques. Consequently we have sought to develop a system of hormonal stimulation that will ensure the delivery of offspring more prepared for extrauterine life. Here we examine deliveries outcome in sheep carrying in vitro-produced and nuclear transfer (NT) embryos in comparison to artificially inseminated and naturally mated control ewes. All groups (excluding NT, which received one treatment) were subjected to one of two hormonal treatments for induction of delivery, whereas the third part of each group was left without any treatment. The first (commonly used for naturally mated ewes) dexamethasone treatment did not solve a majority of parturition disturbances, and actually the number of deliveries necessitating assistance was reduced (P < 0.05) by this treatment in the control group. On the other hand, combined estradiol plus betamethasone stimulation (E + B) solved a majority of complications regarding delivery performance such as lack of the preparation of the mammary gland, low myometrial contractility, insufficient cervical ripening, and impaired maternal behavior. Moreover, substantial reduction of neonatal mortality was observed following the combined treatment. In conclusion, the E + B induction of delivery overcame the majority of physiological and behavioral intrapartum failures of sheep foster mothers and increased the survival of offspring, and thus can be recommended as a safe method for inducing delivery in foster mothers carrying in vitro-generated embryos.

Animals↗
PubMed2002

Preservation of the wild European mouflon: the first example of genetic management using a complete program of reproductive biotechnologies.

Although the potential use of reproductive biotechnologies for safeguarding endangered wildlife species is undoubted, practical efforts have met with limited success to date. In those instances in which modern technologies have been adapted to rescuing rare or endangered species, procedures have been applied piecemeal, and no consistent breeding program based on reproductive biotechnologies has been undertaken. Here we describe for the first time the rescue of an endangered species, the European mouflon (Ovis orientalis musimon), by the application of an integrated package of reproductive biotechnologies. This genetic management extended from the initial collection of gametes, through the in vitro production of embryos and interspecific transfer, to the birth of healthy mouflon offspring. In addition, a genetic resource bank for the European mouflon was established, with cryopreserved sperm, embryos, and somatic cells.

Animals↗
PubMed2002

Nuclei of nonviable ovine somatic cells develop into lambs after nuclear transplantation.

Here we report on the successful reprogramming of nuclei from somatic cells rendered nonviable by heat treatment. Granulosa cells from adult sheep were heated to nonphysiological temperatures (55 degrees C or 75 degrees C) before their nuclei were injected into enucleated metaphase II oocytes. Reprogramming was demonstrated by the capacity of the reconstructed embryos to develop to the blastocyst stage in vitro and into fetuses and viable offspring in suitable foster mothers. To our knowledge, this is the first report of cloned mammalian offspring originating from nonviable cells. In addition, our experiments show that heat-treating donor nuclei destabilizes higher-order features of chromatin (but leaves intact its nucleosomal organization) and results in a high proportion of reconstructed embryos developing to the blastocyst stage and beyond.

Animals↗
PubMedDate not supplied

Living with loss: dementia and the family caregiver.

Two focus group interviews with 15 relatives, investigated family caregivers' perceptions of having a relative in a dementia care unit. Data analysis revealed the significant theme of living with loss. The results demonstrate that the burden of care giving creates growing stress and tension that continues even when the family member is placed into a residential care setting. The findings suggest that health professionals must be prepared to assist family members with the anticipatory grieving of losses that accrue with the changing relationship with the relative and health care staff. Furthermore, there is a need to look for a means of helping and supporting family caregivers so that they can develop a sense of satisfaction and accomplishment in their care giving role.

Adaptation, Psychological↗