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S Healey

Publications and source records attributed to S Healey.

17 recordsLinked to original sources
PubMed2005

Genetic, functional, and histopathological evaluation of two C-terminal BRCA1 missense variants.

BACKGROUND: The vast majority of BRCA1 missense sequence variants remain uncharacterized for their possible effect on protein expression and function, and therefore are unclassified in terms of their pathogenicity. BRCA1 plays diverse cellular roles and it is unlikely that any single functional assay will accurately reflect the total cellular implications of missense mutations in this gene. OBJECTIVE: To elucidate the effect of two BRCA1 variants, 5236G>C (G1706A) and 5242C>A (A1708E) on BRCA1 function, and to survey the relative usefulness of several assays to direct the characterisation of other unclassified variants in BRCA genes. METHODS AND RESULTS: Data from a range of bioinformatic, genetic, and histopathological analyses, and in vitro functional assays indicated that the 1708E variant was associated with the disruption of different cellular functions of BRCA1. In transient transfection experiments in T47D and 293T cells, the 1708E product was mislocalised to the cytoplasm and induced centrosome amplification in 293T cells. The 1708E variant also failed to transactivate transcription of reporter constructs in mammalian transcriptional transactivation assays. In contrast, the 1706A variant displayed a phenotype comparable to wildtype BRCA1 in these assays. Consistent with functional data, tumours from 1708E carriers showed typical BRCA1 pathology, while tumour material from 1706A carriers displayed few histopathological features associated with BRCA1 related tumours. CONCLUSIONS: A comprehensive range of genetic, bioinformatic, and functional analyses have been combined for the characterisation of BRCA1 unclassified sequence variants. Consistent with the functional analyses, the combined odds of causality calculated for the 1706A variant after multifactorial likelihood analysis (1:142) indicates a definitive classification of this variant as "benign". In contrast, functional assays of the 1708E variant indicate that it is pathogenic, possibly through subcellular mislocalisation. However, the combined odds of 262:1 in favour of causality of this variant does not meet the minimal ratio of 1000:1 for classification as pathogenic, and A1708E remains formally designated as unclassified. Our findings highlight the importance of comprehensive genetic information, together with detailed functional analysis for the definitive categorisation of unclassified sequence variants. This combination of analyses may have direct application to the characterisation of other unclassified variants in BRCA1 and BRCA2.

Adult↗
PubMed2003

Coverage of work related fatalities in Australia by compensation and occupational health and safety agencies.

AIMS: To determine the levels of coverage of work related traumatic deaths by official occupational health and safety (OHS) and compensation agencies in Australia, to allow better understanding and interpretation of officially available statistics. METHODS: The analysis was part of a much larger study of all work related fatalities that occurred in Australia during the four year period 1989 to 1992 inclusive and which was based on information from coroners' files. For the current study, State, Territory, and Commonwealth OHS and compensation agencies were asked to supply unit record information for all deaths identified by the jurisdictions as being due to non-suicide traumatic causes and which were identified by them as being work related, using whatever definitions the agencies were using at the relevant time. This information was matched to cases identified during the main study. RESULTS: The percentage of working deaths not covered by any agency was 34%. Only 35% of working deaths were covered by an OHS agency, while 57% were covered by a compensation agency. The OHS agencies had minimal coverage of work related deaths that occurred on the road (to workers (8%) or commuters (3%)), whereas the compensation system covered these deaths better than those of workers in incidents that occurred in a workplace (65% versus 53%). There was virtually no coverage of bystanders (less than 8%) by either type of agency. There was marked variation in the level of coverage depending on the industry, occupation, and employment status of the workers, and the type of injury event involved in the incident. CONCLUSIONS: When using data from official sources, the significant limitations in coverage identified in this paper need to be taken into account. Future surveillance, arising from a computerised National Coroners Information System, should result in improved coverage of work related traumatic deaths in Australia.

Accidents, Occupational↗
PubMed2001

Spinocerebellar ataxia type 7: a distinctive form of autosomal dominant cerebellar ataxia with retinopathy and marked genetic anticipation.

When a child presents with progressive ataxia, there is a broad differential diagnosis and a very long list of potential investigations. Spinocerebellar ataxia type 7 presenting in infancy is a rare condition where a presumptive diagnosis can be made based on the clinical features alone. These include rapidly progressive ataxia, retinopathy and autosomal dominant inheritance with marked genetic anticipation of paternal origin. The father of the infant may manifest minimal symptoms at a time when the infant is severely affected. Diagnosis is confirmed by the demonstration of an expansion of a CAG repeat in the coding region of the gene on chromosome 3p. We present a case to illustrate the diagnostic difficulties. Antenatal diagnosis was performed in two subsequent pregnancies.

Fatal Outcome↗
PubMed1999

Investigation of a cryptic interstitial duplication involving the Prader-Willi/Angelman syndrome critical region.

A 3-year-old female referred with developmental delay, hypotonia and seizures was found to have a cryptic interstitial duplication of the Prader-Willi/Angelman critical region (PWACR). Her clinical features form part of a common phenotype characteristic of PWACR duplications including developmental delay, behavioural problems and speech difficulties. Microsatellite analysis showed that the duplication had arisen de novo, was maternal in origin and involved the entire 4-Mb PWACR between the common deletion breakpoints. The existence of cryptic rearrangements emphasises the need for molecular tests alongside conventional cytogenetics when investigating abnormalities involving this imprinted region.

Angelman Syndrome↗
PubMed1996

Self reported symptoms in the neck and upper limbs in nurses.

This paper describes a cross-sectional study which examines musculoskeletal symptoms in nurses working in two similar units in a residential care centre for the developmentally disabled. Amongst the 30 nurses who were administered the Nordic Questionnaire, neck and upper limb symptoms had resulted in considerable inability to perform work. In contrast, a similar incidence of reported back symptoms in these nurses had not prevented them from doing their work. An examination of the worker's compensation claims made by nurses from the whole facility showed low back claims to be more common than neck and upper limb claims. It appears that nurses are more likely to make a worker's compensation claim for low back symptoms than neck and upper limb symptoms. In other words, worker's compensation claims do not accurately reflect the types of musculoskeletal symptoms actually experienced by nurses and affecting their ability to do their work. Five nurses from each unit were also observed during the entire morning and afternoon shifts to examine the work load and the effects of fatigue on the musculoskeletal system. Heart rate measurements and ratings of perceived exertion were taken. Activities performed and types of transfers carried out were also recorded. Nurses in one of the units had significantly more reported neck and shoulder symptoms than their counterparts. Observations of a sample of five nurses from each unit also showed higher ratings of perceived exertion in this unit. These differences were possibly confounded by the fact that nurses in the unit which experienced these problems were about 8 cm shorter and about 5 kg lighter than their counterparts. Differences in the work practices in the two units, especially methods of manual handling and use of ergonomic interventions were identified as important contributing factors.

Journal Article↗
PubMed1995

Packing products for customers: an ergonomics evaluation of three supermarket checkouts.

The introduction of laser scanners at supermarket checkout areas has resulted in previous ergonomics studies focusing specifically on the scanning process and associated cumulative trauma disorders in the hands and arms. Few studies have evaluated the increased musculoskeletal load and exertion of checkout staff when they are also expected to pack the products into bags for the customers. This paper describes an ergonomics evaluation of three different designs of checkout workstation, which require the operator to stand when they scan the products, pack them into plastic bags and transfer the packed bags to the customer. Musculoskeletal load and exertion associated with the different checkouts were measured using OWAS, heart rate recordings and ratings of perceived exertion. In addition, subjective rankings of the workstations were obtained and the productivity associated with each design examined as part of the evaluation. Some of the variables measured showed significant differences in postural load between the workstations. The results of the evaluation formed the basis of recommendations for an improved workstation design. Some of the suggestions made to reduce postural load and increase productivity include positioning the weigh scale to the side and the bag frame beneath the scanner.

Journal Article↗
PubMed1994

Distinct phenotype in maternal uniparental disomy of chromosome 14.

We report on the occurrence of maternal uniparental disomy for chromosome 14 (mUPD14) in a 4-year-old girl with a de novo Robertsonian translocation, 45,XX,t (13q,14q). The child has arrested hydrocephalus, short stature, minor anomalies, small hands with hyperextensible joints, and mild to moderate developmental delay. Comparison of her phenotype with those of three previously described individuals show some common distinct traits which suggest a mUPD14 syndrome.

Abnormalities, Multiple↗
PubMed1994

Evaluation of the seating of Qantas flight deck crew.

In 1985 Qantas Airways (Australia) requested an ergonomics assessment of three pilots' seats so that one could be selected for fitting in all new aircraft as well replacement in existing aircraft. The Ipeco seat was chosen. In 1991, after all aircraft were fitted with the Ipeco seats, the company then requested a further evaluation of the seat to see if it was acceptable to the pilots and if there were any outstanding problems. A seat feature checklist plus a body chart discomfort rating scale was given to the total crew of 1030 pilots. The results from the 202 respondents indicated that although the pilots found the Ipeco seat an improvement on the Weber seat there were some modifications required. The main problems included insufficient adjustment range of the lumbar support area and the thigh supports, and infrequent replacement of the seat cushion. The body charts supported the checklist results in that the main areas of discomfort indicated were the buttocks and low back. Recommendations for improvements in design of the Ipeco seat, training in use and maintenance are presented. The method used in this study has application for field assessment of seating in a wide range of occupations, particularly bus drivers, truck drivers and train drivers, who spend long hours seated without being able to take breaks.

Journal Article↗
PubMed1993

Reproductive hormone genes in mothers of spontaneous dizygotic twins: an association study.

There are important genetic influences on the tendency to dizygotic (DZ) twinning and it is a plausible hypothesis that these reside in one or more of the genes coding for the major reproductive hormones. We used Southern analysis of DNA from 50 young (< 32) mothers of DZ twins, who also had a family history of DZ twinning, and 50 controls, to examine allele frequencies of five restriction fragment length polymorphisms (RFLPs) in four hormone genes coding for follicle stimulating hormone beta (FSH beta), chorionic gonadotropin beta (CG beta), inhibin beta B and gonadotropin releasing hormone (GnRH). Comparison of allele frequencies revealed no significant differences between DZ twin mothers and controls. However this does not rule out the role of these genes in the hereditary tendency of multiple ovulation in humans, since absence of linkage disequilibrium does not imply absence of linkage.

Adult↗
PubMed1993

Exclusion of APC and MCC as the gene defect in one family with familial juvenile polyposis.

BACKGROUND: In familial juvenile polyposis, multiple juvenile polyps occur throughout the colon. The genetic defect has not been characterized. The risk of colon cancer is increased, although the magnitude of the increased risk is controversial. The hypothesis of this study was that the genetic defect is within a tumor suppressor gene, possibly one already known to be inactivated in colorectal neoplasia. METHODS: Linkage analysis using the short tandem repeat polymorphism D5S346 was performed to determine if juvenile polyposis was linked to either APC (adenomatous polyposis coli) or MCC (mutated in colorectal carcinoma) genes within a single large family. RESULTS: A family in which eight subjects have been affected by juvenile polyposis over three generations is described. Six affected subjects had colectomies in childhood, but the two who have so far survived beyond 35 years of age have developed adenocarcinoma of the jejunum. Within this family, linkage analysis excluded linkage of the juvenile polyposis trait to either APC or MCC. CONCLUSIONS: In a family with juvenile polyposis with a clear predisposition to malignancy, including carcinoma of the jejunum, APC and MCC were not the defective genes causing the condition.

Adenomatous Polyposis Coli↗
PubMed1991

Leukotriene B4 promotes phospholipid acylation in human neutrophils.

The present study was undertaken to test the hypothesis that leukotriene B4 (LTB4) may promote extracellular fatty acid incorporation into neutrophil choline glycerophospholipids (PC) to replenish phospholipids after deacylation. Incubation of human neutrophils with LTB4 (1.5 to 150 nM) for 1 to 5 min resulted in increased fatty acid incorporation into phosphatidylinositol (PI), diacyl-sn-glycero-3-phosphocholine (diacyl-GPC) and alkylacyl-GPC. The magnitude of stimulation (percentage of control) of fatty acid incorporation appears to reflect increased activity of the acyltransferase catalyzing acylation of the respective lysophospholipids. LTB4 stimulation of arachidonic acid incorporation into PI was greater than into PC, whereas the stimulation of palmitic acid incorporation into PC was greater than into PI. LTB4 stimulated phosphatidic acid labeling by palmitic acid but not by arachidonic acid. LTB4 and 1-O-alkyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine (cPAF) exhibited a similar stimulatory effect on fatty acid incorporation into the PC fraction. Phosphate analysis could not detect changes in the mass of PI or of PC in neutrophils exposed to LTB4 or cPAF. The results suggest that increased fatty acid incorporation into phospholipids in LTB4-activated neutrophils reflects activation of phospholipase A2 and acyltransferases as well as of de novo phospholipid synthesis.

Acylation↗
PubMed1990

A randomised controlled trial of counseling in a workplace setting for coronary heart disease risk factor modification: effects on blood pressure.

This paper reviews a prospective study of occupational factors in coronary heart disease risk incorporated in a randomised controlled trial of a worksite based occupational health nurse counseling program for reducing coronary heart disease risk factors. The aim of the trial was to evaluate the longterm effectiveness of the counseling program in persons with mildly elevated risk factor levels. Of the 2,489 Australian government employees with mildly elevated risk factor levels who entered the intervention trial, 1,937 (78%) attended a followup examination three years later. This paper reports on changes in systolic and diastolic blood pressure. Multiple linear regression models were used with three-year blood pressure reduction as the dependent variable, intervention status as the main determinant, and sex, age, initial risk level and initial blood pressure as covariates. Although systolic and diastolic blood pressure fell in both the intervention and control groups, intervention was significantly associated with systolic blood pressure change only.

Adult↗
PubMed1989

Evaluation of a worksite programme for the modification of cardiovascular risk factors.

This article reports on the long-term results of a randomized controlled trial of non-pharmacological intervention for mildly-elevated levels of cardiovascular risk factors. The intervention consisted of individual counselling by occupational health professionals. From a population of 4607 volunteers who were working for Australian government organizations, a sample of 2489 subjects met the eligibility criteria for the trial, and 1937 subjects were available for follow-up examination three years later. Changes in the levels of risk factors favoured the interventional group marginally and appeared to vary with the sex, age and occupation of the subjects. A significant effect of intervention was noted for systolic blood pressure levels; however, although this interventional effect was more pronounced in men of 40 years of age or over and in administrative workers, clinically it was small. The results suggest that individual counselling, as undertaken in this study, generally is not effective in the long-term modification of mildly-elevated cardiovascular risk factors.

Adult↗
PubMed1979

Prevalence of sleep disorders in the Los Angeles metropolitan area.

The authors determined the prevalence of sleep disorders in a general population through a survey of 1,006 representative households in the Los Angeles metropolitan area. They found an overall prevalence of current or previous sleep disorders in adults of 52.1%. Specifically, they found a 42.5% prevalence of insomnia, 11.2% of nightmares, 7.1% of excessive sleep, 5.3% of sleeptalking, and 2.5% of sleepwalking. These conditions were often chronic and usually started early in life. Insomnia was more frequent in older people, particularly older women, and in people of lower educational socioeconomic status. Insomnia, nightmares, and hypersomnia were correlated with more frequent general physical and mental health problems.

Adolescent↗
PubMed1976

Personality patterns in insomnia. Theoretical implications.

Subjects with a primary complaint of insomnia (N = 124) were evaluated with Minnesota Multiphasic Personality Inventories (MMPIs). A high percentage of subjects (85%) had one or more MMPI scales elevated to a pathological degree. The scales most elevated were, in order. 2 (depression), 7 (psychasthenia), and 3 (conversion hysteria). A striking finding was the preponderance of depression. This was indicated by the frequency in which scale 2 was elevated above 70, the frequency in which this this scale had the highest elevation, and the frequency of MMPI code types that included scale 2. Four common MMPI code types representing various types of depression were noted, indicating considerable homogeneity for code types in this sample. The predominant personality styles in this sample were characterized by the internalization of psychological distrubances rather than by acting out or aggression. We propose that this internalization produces a state of constant emotional arousal and resultant physiological activation and that this process is a psychophysiological mechansim underlyling insomnia.

Adolescent↗