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Biomedical subjects

S Kelly

Publications and source records attributed to S Kelly.

At least 73 records · Page 4Linked to original sources
PubMed2000

Crystallization and preliminary diffraction studies of a truncated form of a novel protease from spores of Bacillus megaterium.

During germination of spores of Bacillus species, a novel protease termed GPR initiates the degradation of a group of small acid-soluble spore proteins which protect the dormant spore's DNA from damage. Trypsin digestion of the zymogen of B. megaterium GPR removes approximately 15 kDa from the C-terminal end of the 46 kDa zymogen subunit, leaving a 30 kDa subunit. Single crystals of this truncated form of GPR have been obtained by the vapor-diffusion method using PEG 4000 as a precipitating agent. The crystals belong to the monoclinic space group P2(1), with unit-cell parameters a = 67.99, b = 105.34, c = 108.63 A, beta = 95.68 degrees. The cryofrozen crystals diffract X-rays to about 3.3 A using synchrotron radiation.

Bacillus megaterium↗
PubMed2000

Childhood cancer in the offspring of male sawmill workers occupationally exposed to chlorophenate fungicides.

The objective of this study was to determine whether paternal occupational exposure to chlorophenol fungicides and their dioxin contaminants is associated with childhood cancer in the offspring of sawmill workers. We used data from 23,829 British Columbian sawmill workers employed for at least 1 continuous year between 1950 and 1985 in 11 sawmills that used chlorophenates. Probabilistic linkage of the sawmill worker cohort to the provincial marriage and birth files produced an offspring cohort of 19,674 children born at least 1 year after the initiation of employment in the period 1952-1988. We then linked the offspring cohort to the British Columbia Cancer Registry. We included all malignancies in cases younger than 20 years of age that appeared on the cancer registry between 1969 and 1993. We calculated standardized incidence ratios (SIRs) using the British Columbia population as a reference. A nested case-control analysis assessed the effects of paternal cumulative exposure and windows of exposure on the risk of developing cancer in the offspring. We identified 40 cases of cancer during 259,919 person-years of follow-up. The all-cancer SIR was 1.0 [95% confidence interval (CI), 0.7-1.4]; the SIR for leukemia was 1.0 (CI, 0.5-1.8); and the SIR for brain cancer was 1.3 (CI, 0.6-2.5). The nested case-control analysis showed slightly increased risks in the highest categories of chlorophenol exposure, although none was statistically significant. Our analyses provide little evidence to support a relationship between the risk of childhood cancer and paternal occupational exposure to chlorophenate fungicides in British Columbian sawmills.

Adolescent↗
PubMed2000

A rapid interferent-free assay for the determination of LD-1 in biological samples.

A highly specific enzyme linked immunosorbent assay (ELISA) for the detection of lactate dehydrogenase-1 (LD-1) has been developed. A competition assay is described with polyclonal antibody to LD-1 passively adsorbed on an ELISA 96-well plate, with non-labelled and labelled LD-1 antigen competing. The LD-1 antigen is conjugated to alkaline phosphatase (ALP) using the one step glutaraldehyde method. A linear range of 10-4000 U/L was obtained, and cross-reactivity was only observed with LD-2. It was possible to eliminate this cross-reactivity by carrying out the final incubation step at 65 degrees C. The developed assay was applied to the analysis of spiked serum and plasma samples and the recoveries obtained were acceptable.

Alkaline Phosphatase↗
PubMed2000

Downsizing and industrial restructuring in related to changes in psychosocial conditions of work in British Columbia sawmills.

OBJECTIVES: This paper investigates changes in the psychosocial and physical work conditions of the sawmill industry in British Columbia, Canada, over the past 35 years. METHODS: Shifts in work conditions were examined within the context of historical changes in sawmill labor demography and job taxonomy as the industry was both downsized and restructured, largely in response to an economic recession in the early 1980s. RESULTS AND CONCLUSIONS: Downsizing eliminated approximately 60% of the work force and 1/4 of sawmill job titles. Although all the job categories in restructured sawmills showed increased levels of control, the gradient in control across job categories was steeper in 1997 than in 1965; this change may have important health implications particularly for the unskilled workers in the restructured mills.

British Columbia↗
PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗
PubMed1999

Increased neuronal damage in apolipoprotein E-deficient mice following global ischaemia.

There is accumulating evidence that apolipoprotein E (apoE) plays a role in regulating the response to and outcome following brain injury. The present study compared the histological outcome and recovery following an episode of global ischaemia in apoE-deficient mice and wild-type littermates (12-week-old males, n = 8 per group). Transient global ischaemia was induced for a period of 17 min and the animals were allowed to recover for 72 h. Transient global ischaemia induced selective neuronal degeneration in several brain regions in wild-type mice. There was statistically significant increased ischaemic neuronal damage in apoE-deficient mice compared with wild-type mice in six of the seven regions examined (hippocampal regions CA1, CA3/CA4 and dentate gyrus; thalamus; cortex and caudate nucleus; P < 0.05). The data substantiate a role for apoE in modifying the response of the CNS to acute injury.

Alleles↗
PubMed1999

Systematic analysis of yeast strains with possible defects in lipid metabolism.

Lipids are essential components of all living cells because they are obligate components of biological membranes, and serve as energy reserves and second messengers. Many but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of the yeast Saccharomyces cerevisiae have been cloned and gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes or the turnover and degradation of complex lipids. To obtain more insight into lipid metabolism, regulation of lipid biosynthesis and the role of lipids in organellar membranes, a group of five European laboratories established methods suitable to screen for novel genes of the yeast Saccharomyces cerevisiae involved in these processes. These investigations were performed within EUROFAN (European Function Analysis Network), a European initiative to identify the functions of unassigned open reading frames that had been detected during the Yeast Genome Sequencing Project. First, the methods required for the complete lipid analysis of yeast cells based on chromatographic techniques were established and standardized. The reliability of these methods was demonstrated using tester strains with established defects in lipid metabolism. During these investigations it was demonstrated that different wild-type strains, among them FY1679, CEN.PK2-1C and W303, exhibit marked differences in lipid content and lipid composition. Second, several candidate genes which were assumed to encode proteins involved in lipid metabolism were selected, based on their homology to genes of known function. Finally, lipid composition of mutant strains deleted of the respective open reading frames was determined. For some genes we found evidence suggesting a possible role in lipid metabolism.

Antifungal Agents↗
PubMed1999

Glycated hemoglobin as an indicator of social environmental stress among indigenous versus westernized populations.

BACKGROUND: This study assessed whether glycated hemoglobin concentration, an indicator of psychogenic stress, differs between indigenous populations and non-indigenous reference groups. METHODS: Multivariate and stratified analyses were undertaken of cross-sectional data from multi-center community-based diabetes diagnostic and risk factor screening initiatives in Canada and Australia. Population groups were Australian Aborigines (n = 116), Torres Strait Islanders (n = 156), Native Canadians (n = 155), Greek migrants to Australia (n = 117), and Caucasian Australians (n = 67). Measurements included fasting glycated hemoglobin (HbA(1c)) concentration, fasting and 2-h post-load glucose concentrations, body mass index, waist-to-hip ratio, and demographic variables. RESULTS: Mean HbA(1c) concentrations were greater for indigenous groups than for Greek migrants and Caucasian Australians (P < 0. 0001). The covariate adjusted indigenous versus non-indigenous difference (95% CI) was 0.90 (0.58-1.22) percentage units, 18.2% higher for indigenous people. Stratified analyses indicated greater HbA(1c) for indigenous than for non-indigenous persons with normoglycemia (P = 0.009), impaired glucose tolerance (P = 0.097), and diabetes (P < 0.0001). CONCLUSIONS: HbA(1c) concentrations are greater for indigenous than for non-indigenous groups. Social changes, low control, and living conditions associated with westernization may be inherently stressful at the biological level for indigenous populations in westernized countries.

Acculturation↗
PubMed1999

An instrument for the multiparameter assessment of speech.

This paper describes the development of SNORS+, a clinical, user-friendly instrument for measurement of the articulators during speech. The design criteria for the instrument were based upon a wide-ranging review of current practice and available techniques. SNORS+ allows objective assessment of the function and co-ordination of key articulators. Appropriate targeting of therapy is therefore possible. Visual feedback is provided, for therapy, and an objective measurement of outcome is easily obtained. Preliminary results are presented. These suggest that the instrument will prove extremely useful in the assessment and management of many speech disorders.

Adult↗
PubMed1999

Identifying strategies for managing urinary incontinence with women who have multiple sclerosis.

The aim of this pilot project was to identify strategies for managing incontinence with women who have multiple sclerosis (MS). The project used the formation of a group in which eight women with MS and four Continence Nurse Advisers (CNAs) and the first author were brought together. In the course of the research process, the women found a voice on a topic previously thought of as taboo. When they realized that they had suffered alone and in silence they felt empowered to act. In this way, the methodology evolved from group work into a participatory action research process (PAR), as the group initiated action. Participants formed a self-help group, and continued to meet with each other after the research had run its course.

Activities of Daily Living↗
PubMed1999

Implementing and sustaining evidence-based clinical practice in Australia: the Evidence Based Clinical Practice Research Initiative.

Evidence-based medicine is a process by which clinicians translate clinical information needs into answerable questions, track down answers to those needs as efficiently and effectively as possible using the best evidence available, apply the information to patients and evaluate their performance. Implementing evidence-based medicine is fragmented and variable. The National Health and Medical Research Council of Australia has implemented a research program to determine successful strategies for implementation and sustaining of evidence-based clinical practice. In addition this research program will help to answer whether evidence-based practice improves patient outcomes. This paper describes this program and other strategies that improve the application of evidence-based practice in clinical settings.

Australia↗
PubMed1999

The nature of the attenuation of Salmonella typhimurium strains expressing human papillomavirus type 16 virus-like particles determines the systemic and mucosal antibody responses in nasally immunized mice.

We have recently shown by using a recombinant Salmonella typhimurium PhoPc strain in mice the feasibility of using a Salmonella-based vaccine to prevent infection by the genital human papillomavirus type 16 (HPV16). Here, we compare the HPV16-specific antibody responses elicited by nasal immunization with recombinant S. typhimurium strains harboring attenuations that, in contrast to PhoPc, are suitable for human use. For this purpose, chi4989 (Deltacya Deltacrp) and chi4990 [Deltacya Delta(crp-cdt)] were constructed in the ATCC 14028 genetic background, and comparison was made with the isogenic PhoPc and PhoP- strains. Although the levels of expression of HPV16 virus-like particle (VLP) were similar in all strains, only PhoPc HPV16 induced sustained specific antibody responses after nasal immunization, while all strains induced high antibody responses with a single nasal immunization when an unrelated viral hepatitis B core antigen was expressed. The level of the specific antibody responses induced did not correlate with the number of recombinant bacteria surviving in various organs 2 weeks after immunization. Our data suggest that the immunogenicity of attenuated Salmonella vaccine strains does not correlate with either the number of persisting bacteria after immunization or the levels of in vitro expression of the antigen carried. Rather, the PhoPc phenotype appears to provide the unique ability in Salmonella to induce immune responses against HPV16 VLPs.

Animals↗
PubMed1999

Cost-effective methods for isolation of Salmonella enterica in the clinical laboratory.

Data from 8,717 fecal specimens indicate that primary inoculation of xylose lysine deoxycholate (XLD) agar may enhance the speed, but not the sensitivity, of isolation of Salmonella enterica over that achieved with Selenite enrichment only. Plating of Selenite broth onto both brilliant green and XLD agar offers no advantage over plating onto XLD alone.

Agar↗
PubMed1999

Polishing.

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Dental Prophylaxis↗