PubMed Health⌕ Search

Biomedical subjects

S Dwyer

Publications and source records attributed to S Dwyer.

14 recordsLinked to original sources
PubMed2004

Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1).

CONTEXT: Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study. OBJECTIVES: To confirm DTNBP1 as a schizophrenia susceptibility gene, to identify and replicate specific risk and protective haplotypes, and to explore relationships between DTNBP1 and the phenotype. DESIGN: Genetic association study based on mutation detection and case-control analysis. SETTING: All subjects were unrelated and ascertained from general (secondary care) psychiatric inpatient and outpatient services. PARTICIPANTS: The Cardiff, Wales, sample included 708 white subjects from the United Kingdom and Ireland (221 females) who met DSM-IV criteria for schizophrenia and were individually matched for age, sex, and ethnicity to 711 blood donor controls (233 females). Mean +/- SD age at first psychiatric contact for cases was 23.6 +/- 7.7 years; mean age at ascertainment was 41.8 +/- 13.5 years. The Dublin, Ireland, sample included 219 white subjects from the Republic of Ireland who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and 231 controls. The mean age of the Irish cases was 46.0 +/- 8.5 years; mean age at first psychiatric contact was 25.2 +/- 12.4 years. MAIN OUTCOME MEASURE: Evidence for association between the DTNBP1 locus and schizophrenia. RESULTS: In the Cardiff sample, there was no evidence for association with previously implicated haplotypes but strong evidence for association with multiple novel haplotypes. Maximum evidence was found for a novel 3-marker haplotype (global P<.001), composed of 1 risk haplotype (P =.01) and 2 protective haplotypes, 1 common (P =.006) and 1 rare (P<.001). Specific risk and protective haplotypes were replicated in the Dublin sample (P =.02,.047, and.006, respectively). The only phenotypic variable associated with any haplotype was between the common protective haplotype and higher educational achievement (P =.02, corrected for multiple tests). CONCLUSIONS: DTNBP1 is a susceptibility gene for schizophrenia. Specific risk and protective haplotypes were identified and replicated. Association with educational achievement may suggest protection mediated by IQ, although this needs to be confirmed in an independent data set.

Adult↗
PubMed2004

Health and aesthetic impacts of copper corrosion on drinking water.

Traditional research has focused on the visible effects of corrosion--failures, leaks, and financial debits--and often overlooked the more hidden health and aesthetic aspects. Clearly, corrosion of copper pipe can lead to levels of copper in the drinking water that exceed health guidelines and cause bitter or metallic tasting water. Because water will continue to be conveyed to consumers worldwide through metal pipes, the water industry has to consider both the effects of water quality on corrosion and the effects of corrosion on water quality. Integrating four key factors--chemical/biological causes, economics, health and aesthetics--is critical for managing the distribution system to produce safe water that consumers will use with confidence. As technological developments improve copper pipes to minimize scaling and corrosion, it is essential to consider the health and aesthetic effects on an equal plane with chemical/biological causes and economics to produce water that is acceptable for public consumption.

Copper↗
PubMed2000

Use of nitric oxide for decompensated right ventricular failure and circulatory shock after cardiac arrest.

We describe a case of peri-operative cardiac arrest, severe right ventricular failure and pulmonary hypertension in a 60-yr-old woman with interstitial pulmonary fibrosis. Inhaled nitric oxide therapy rapidly improved arterial oxygenation and haemodynamic variables, allowing recovery and weaning from mechanical ventilation. Subsequently, the patient was discharged from the cardiac intensive care unit.

Anesthesia, General↗
PubMed1997

The health-promoting workplace: an integrative perspective.

The workplace is an important setting, affecting the physical, mental, economic and social wellbeing of workers, and, in turn, their families. Health of workers has many determinants, and a multidisciplinary, integrated approach is important. An overview of trends in workplace health promotion shows that current thinking has changed from a narrowly based risk-factors approach aimed at individual behaviour changes, to an integrative approach aimed at creating health-promoting workplaces. The health-promoting workplace has 'an all-encompassing approach that empowers workers and employers to improve all facets of their health'. There are gaps in knowledge, at the state and national levels, relevant to the planning and assessment of workplace health. A national information network is needed to facilitate better links between public health practitioners and researchers in advancing the health of working Australians.

Adult↗
PubMed1997

Improving delivery of a health-promoting-environments program: experiences from Queensland Health.

The purpose of this paper is to outline the key components of a statewide multisite health-promoting-environments program. Contemporary health-promotion programs in settings such as schools, workplaces and hospitals use organisational development theory to address the health issues of the setting, including the physical environment, the organisational environment, and the specific health needs of the employees and consumers of the service. Program principles include management of each project by the participant organisation or site (for example, a school or workplace), using resources available within the organisation and the local community, voluntary participation, social justice and participant-based priority setting, and evaluation and monitoring. Adoption of these principles implies a shift in the role of the health worker from implementer to facilitator. Based on the experience of Queensland Health, it is proposed that the essential building blocks of the health-promoting-environments program are an intersectoral policy base, a model for action, training and resources, local facilitators, support from local organisations, a supportive network of sites, marketing of the program, and a state-based evaluation and monitoring system. The program in Queensland was able to develop a significant number of these components over the 1990-1996 period. In regard to evaluation, process measures can be built around the program components; however, further research is required for development of impact indicators and benchmarks on quality.

Community Health Services↗
PubMed1995

Bathing persons with dementia.

In the care of persons with Alzheimer's disease and related disorders, bathing frequently poses a formidable challenge for caregivers. This article reports the results of a consensus conference on techniques to reduce disruptive behaviors during bathing, and to make the process less stressful for persons with dementia.

Baths↗
PubMed1994

Technology transfer in digital mammography. Report of the Joint National Cancer Institute-National Aeronautics and Space Administration workshop of May 19-20, 1993.

Digital mammography is one of the most promising novel technologies for further improvement of early detection of breast cancer, offering important potential advantages: 1) improved image quality; 2) digital image processing for improved lesion contrast; 3) computer-aided diagnosis for enhanced radiologic interpretation; and 4) teleradiology for facilitated radiologic consultation. The Diagnostic Imaging Research Branch of the National Cancer Institute (NCI) recently funded an international, multidisciplinary, multi-institutional Digital Mammography Development Group for collaborations between NCI, the academic community, and industry to facilitate the integrated development and implementation of digital mammographic systems. Currently, however, digital mammography faces a number of fundamental technological roadblocks: 1) cost-effective digital detectors and displays for imaging systems; 2) the need for novel algorithms for image processing and computer-aided diagnosis; and 3) high performance, low cost digital networks to provide an "information superhighway" for teleradiology. To solve some of these technological problems, the Diagnostic Imaging Research Branch of NCI joined efforts with the Technology Transfer Division of the National Aeronautics and Space Administration to pursue a federal technology transfer program in digital mammography. The authors discuss the findings and recommendations of the workshop entitled "Technology Transfer in Digital Mammography," which was organized and held jointly by the NCI and the National Aeronautics and Space Administration in May, 1993. Numerous innovative technologies of varying degree of promise for digital mammography were presented at the conference. In this article, specific technologies presented at the workshop by the federal and federally-supported laboratories are described, and critiques of these technologies by the leaders of the medical imaging community are presented.

Breast Neoplasms↗
PubMed1992

A genetic system for studying the activity of a proteolytic enzyme.

We describe a genetic system for monitoring the activity of a specific proteolytic enzyme by taking advantage of the properties of the yeast transcriptional activator GAL4. The GAL4 protein contains two separable and functionally essential domains: the amino-terminal DNA binding domain and the carboxyl-terminal transcriptional activating domain. We constructed two hybrid proteins by inserting between the DNA binding domain and the activation domain of GAL4 either (i) a self-cleaving protease (3C protease of a picornavirus, coxsackievirus B3) or (ii) a mutant form of the protease that is unable to cleave. We show that, although the hybrid protein containing the mutant protease activates transcription of GAL1-lacZ reporter gene, the hybrid protein bearing the wild-type protease is proteolytically cleaved and fails to activate transcription. Our approach to monitor the proteolytic activity could be used to develop simple genetic systems to study other proteases.

Amino Acid Sequence↗
PubMed1991

Expression of functional beta-galactosidase containing the coxsackievirus 3C protease as an internal fusion.

Alpha complementation of beta-galactosidase (beta gal) is intracistronic and requires interaction between the alpha donor region (residues 3-41) and alpha acceptor fragment (produced by M15). We have constructed two plasmids which direct the synthesis of hybrid beta gal: coxsackievirus proteins in Escherichia coli. One plasmid, pBD1045, encodes an enzymatically active 3C protease of coxsackievirus B3 fused between the amino-terminal 79 amino acids of beta gal (containing the alpha donor region) and amino acids 80 to 1023 (alpha acceptor region). A second plasmid, pBD1043 encodes an inactive 3C protease and results in a fusion of 260 coxsackievirus amino acids between residues 79 and 80 of the beta gal monomer. Both hybrid proteins expressed by these constructs have beta-galactosidase activity regardless of whether the viral protease (183 amino acids) is autocatalytically cleaved out of the chimeric protein (pBD1045) or remains as part of a fusion protein (pBD1043). The implications of these results for structural flexibility of the complemented beta-galactosidase enzyme are discussed.

3C Viral Proteases↗
PubMed1991

Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila.

A long-lived (L) strain of Drosophila melanogaster, derived from a normal-lived (R) strain by artificial selection, has a significantly different adult longevity. Previous work has shown that 1) the two strains age in the same manner, 2) the major genes responsible for much of the L strain's extended longevity are located on the 3rd chromosome, and 3) the extended longevity phenotype is significantly modulated by the larval environment. In this report, we investigate the resistance of the L and R strains to the lethal effects of dietary paraquat. We show that, within the limitations of our described chromosomal and environmental manipulations, the extended longevity phenotype always accompanies the phenotype of elevated paraquat resistance. In addition, reversed selection applied to the L strain results in the simultaneous decrease of both life span and paraquat resistance. Thus, the presence or absence of the latter phenotype may be used as a bioassay for the presence or absence of the extended longevity phenotype, without any necessary implication of causality. Use of this bioassay should greatly speed up the genetic analysis of this system by allowing us to identify long-lived animals at a young age. Finally, we show that the age-related loss of elevated paraquat resistance in both strains precedes all the other age-related functional decrements which we have previously noted in this system.

Animals↗
PubMedDate not supplied

The design and synthesis of purine inhibitors of CDK2. III.

Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.

Adenine↗