Biomedical subjects
S Chapman
Publications and source records attributed to S Chapman.
Formula one racing and the end of tobacco sponsorship: half pregnant at 350 kph?
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Geoff Bible's class.
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Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase.
Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. Both PKC and GSK-3beta are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPalpha production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3beta. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.
Has the ban on smoking in New South Wales restaurants worked? A comparison of restaurants in Sydney and Melbourne.
OBJECTIVE: To evaluate compliance with a legislative ban on smoking inside restaurants by comparing smoking in Sydney restaurants (where it is legally banned) with smoking in Melbourne restaurants (not subject to a legal ban). DESIGN AND PARTICIPANTS: Unobtrusive observational study of restaurant patrons, and interviews with restaurant staff, carried out by 159 volunteers. SETTING: 78 Sydney restaurants with smoke-free indoor environments (as required by legislation) and 81 Melbourne restaurants not subject to legislation preventing smoking. The study took place from 20-31 October 2000. INTERVENTION: Legislation to ban smoking in indoor areas of restaurants was introduced in New South Wales in September 2000 (about six weeks before our study). OUTCOMES: Observed incidents of smoking inside restaurants; staff attitudes to the ban; customer satisfaction as indicated by comments to staff; staff perceptions of restaurant patronage. RESULTS: No restaurant patrons were seen smoking in 78 Sydney restaurants during 156 hours of observation of 2,646 diners, compared with 176 smokers among 3,014 Melbourne diners over 154 hours of observation. Thirty-one per cent (24/78) of Sydney restaurants had experienced smokers attempting to smoke indoors after the legislation was introduced; 6% (5/78) reported instances of smokers refusing to stop smoking when asked; 79% (62/78) of restaurants had received favourable comments from patrons about the smoke-free law; 81% (63/78) of restaurant staff interviewed either supported or strongly supported the law. Since introduction of the legislation, 76% of restaurants reported normal trade, 14% increased trade, and 9% reduced trade. CONCLUSIONS: Smoke-free restaurants do not require "smoking police" to enforce bans, present few ongoing difficulties for staff, attract many more favourable than unfavourable comments from patrons, and do not adversely affect trade.
Australian bar worker wins payout in passive smoking case.
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A novel strategy for the expression of foreign genes from plant virus vectors.
Potato virus X (PVX)-based vector constructs were generated to investigate the use of an internal ribosome entry site (IRES) sequence to direct translation of a viral gene. The 148-nucleotide IREScp sequence from a crucifer-infecting strain of tobacco mosaic virus was used to direct expression of the PVX coat protein (CP). The IRES was inserted downstream of the gene encoding green fluorescent protein (GFP) and upstream of the PVX CP, in either sense or antisense orientation, such that CP expression depended on ribosome recruitment to the IRES. Stem-loop structures were inserted at either the 3'- or 5'-end of the IRES sequence to investigate its mode of action. In vitro RNA transcripts were inoculated to Nicotiana benthamiana plants and protoplasts: levels of GFP and CP expression were analysed by enzyme-linked immunosorbent assay and the rate of virus cell-to-cell movement was determined by confocal laser scanning microscope imaging of GFP expression. PVX CP was expressed, allowing cell-to-cell movement of virus, from constructs containing the IRES sequence in either orientation, and from the construct containing a stem-loop structure at the 5'-end of the IRES sequence. No CP was expressed from a construct containing a stem-loop at the 3'-end of the IRES sequence. Our results suggest that the IRES sequence is acting in vivo to direct expression of the 3'-proximal open reading frame in a bicistronic mRNA thereby demonstrating the potential of employing IRES sequences for the expression of foreign proteins from plant virus-based vectors.
Prophylaxis against organophosphate poisoning by sustained release of scopolamine and physostigmine.
Protection efficacy of continuous prophylactic administration of physostigmine and scopolamine against sarin-induced toxicity was evaluated previously in guinea pigs. The present study in large animals used Beagle dogs, that serve as an animal model with cholinergic sensitivity similar to that of humans. Pretreatment with physostigmine salicylate and scopolamine hydrochloride at dose rates of 2.5 and 1 microg x kg(-1) x h(-1), respectively, was administered via Alzet mini-osmotic pumps. At the time of exposure, the physostigmine salicylate concentration in plasma was 0.7 ng x ml(-1) and the scopolamine hydrochloride concentration was ca. 0.2 ng x ml(-1), both of which are levels known to be well tolerated in humans. Whole-blood cholinesterase inhibition was 15-20%. This regimen conferred full protection against 2.5 x LD50 i.v. of sarin. Albeit the high-dose exposure, cholinergic toxicity symptoms were mild with no convulsions. About 11-14 min following poisoning the treated animals started to walk and 15-20 min following exposure full recovery was observed and the dogs behaved normally. With higher dose rates of physostigmine salicylate and scopolamine hydrochloride, at plasma concentrations of 2.1 and 0.6 ng x ml(-1), respectively, treated dogs regained normal posture 6-10 min after exposure.
Klippel-Trenaunay-Weber (KTW) syndrome: the use of in utero magnetic resonance imaging (MRI) in a prospective diagnosis.
The diagnosis of the Klippel-Trenaunay-Weber (KTW) syndrome is rarely made antenatally. We report the use of both ultrasound and in utero magnetic resonance imaging (MRI) in the prenatal diagnosis of this syndrome. This is the first report of the use of prenatal MRI in the diagnosis of this condition. There was concordance in the findings of both modalities, with limb hypertrophy, and multiple haemangiomata - both subcutaneous and internally - demonstrated with ultrasound and MRI. The patient elected to terminate the pregnancy because of associated oligohydramnios and a small fetal chest noted at 20 weeks. The postmortem examination confirmed the antenatal diagnosis.
Cerebellar defect associated with Schimke immuno-osseous dysplasia.
UNLABELLED: We report the finding of an absent cerebellar hemisphere and partial absence of the cerebellar vermis in a child with dysmorphic features, spondyloepiphyseal dysplasia, steroid resistant nephrotic syndrome secondary to focal segmental glomerulosclerosis and T-cell lymphopenia (Schimke immuno-osseous dysplasia). These findings have not, to our knowledge, been described before and are likely to represent the consequence of a vascular event either in-utero or in early infancy. CONCLUSION: Cerebral imaging should be performed early in the course of the disease and should be repeated if further neurological events develop.
Identification of the pharmaceutical care issues of rheumatoid arthritis patients in secondary care.
OBJECTIVE: To explore the perceptions of multidisciplinary health care professionals (HCPs) and patients of the pharmaceutical care issues (PCIs) relating to rheumatoid arthritis (RA). DESIGN: Qualitative study using semi-structured one to one interviews and focus groups to explore patient perceptions. Interviews and focus groups were taped and transcribed verbatim, then described and coded for meaning to produce 'in-vivo' codes, which were then grouped to form themes. Nominal group methodology was used to generate and rank a list of HCP perceptions of the key PCIs of RA patients. The PCIs were ranked according to clinical importance and order of occurrence from admission as perceived by the HCP group. SETTING: Rheumatology ward and outpatient clinic in a teaching hospital. MAIN OUTCOME MEASURES: Generation and ranking of PCIs, generation of themes from patient interviews. RESULTS: Optimisation of pain control was identified by the nominal group as being the primary aim for patients on admission and was also the most commonly described symptom by patients. Two PCIs not predicted by the HCPs' nominal group was the frequency of infections and the associated discharge and patients described experiencing 'over-education' by HCPs, which could lead to anxiety. Complementary medicine in conjunction with traditional therapy was raised as a significant health benefit by patients. CONCLUSION: Many patients' views mirrored the PCIs identified by HCPs, but some were not anticipated; the value of patient interviews to ensure appropriate service development was demonstrated. Several PCIs emerged for future incorporation by the multi-disciplinary team into standardised models of pharmaceutical care for use in secondary care and at the secondary/primary care interface for improvement of seamless care. There is a need to target educational interventions and to identify those who will benefit from advice on complementary medicine. Further work is required to develop a tool to identify the educational needs of RA patients and targeting of the information provided. This will help ensure the delivery of pharmaceutical care is designed to match the needs of individual patients.
Sites of phosphorylation in tau and factors affecting their regulation.
The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.
Media reports of rural health and safety: a review of articles published in The Land newspaper.
The Land is one of the main newspapers that service Australia's rural community. A content analysis of reports on health issues in The Land was undertaken for the period April 1998 to October 1999 (76 editions, 10 336 pages). Fifty-four articles were published, with most being about causes of farm injury. Very few articles concerning non-injury health issues facing rural residents were published. People working in health promotion should consider The Land to be an under-utilised vehicle for news and commentary on rural health and safety issues.
Scooter injuries in children.
OBJECTIVES: To study the causes, patterns of injury and use of safety equipment in children presenting with 'push/kick' scooter-related injuries. To draw comparisons with in-line skate, skateboard and bicycle injuries and to suggest strategies for injury prevention. METHODS: A retrospective review of medical data was undertaken for 12 consecutive months to September 2000. All children aged < 15 years who had attended the Sydney Children's Hospital with scooter, in-line skate (rollerblade), skateboard or bicycle injuries were identified. Children with scooter injuries for the latter 6 month period were contacted by telephone and interviewed, together with their parents, using a structured questionnaire. RESULTS: There was a marked rise in the number of scooter injuries from October 1999 to September 2000. Sixty-one per cent of these injuries occurred during the final 3 months of the study period, making scooters the most common cause of injury in the studied groups for this period. Forty-two per cent of scooter injuries were fractures. Only 3% of children used safety equipment at the time of injury, despite 86% owning some form of safety equipment. Children were less likely to use safety equipment with a scooter than with any other form of activity studied. (Chi-squared P=0.000). CONCLUSIONS: Scooters are a common cause of childhood injury, resulting in injury patterns similar to those caused by in-line skates, skateboards and bicycles. Safety equipment is rarely worn when scooters are ridden. Injury patterns and riding styles suggest that if existing guidelines for in-line skating, skateboarding and bicycling are modified and applied to scooters, a reduction in injury numbers may be achieved.
Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits.
PURPOSE: To establish an experimental model for sulfur mustard-induced acute and delayed ocular lesions in rabbits. METHODS: Rabbit eyes were exposed to sulfur mustard (HD) vapor (370, 420 microg/l) for a period of two minutes. A three months follow-up study was carried out, based on the evaluation of clinical, biochemical and histological parameters. RESULTS: HD exposure initiated typical clinical symptoms within 2-6 hrs, characterized by eye closure, eyelid swelling, conjunctival hyperemia, corneal erosions and inflammation. The clinical signs were significantly dose-dependent and reached a peak at 24--72 hrs post exposure. Biochemical evaluation of the aqueous humor exhibited an inflammatory reaction and oxidative stress at 4 hrs after exposure, subsiding at 28 hrs after exposure. Histological examination of corneas at 48 hrs revealed epithelial denudation and marked stromal edema, accompanied by cellular infiltration. Epithelial regeneration started after 72 hrs, and recovery was almost completed within 1--2 weeks, depending on the HD dose. A second phase of pathological processes started as early as two weeks post exposure and was characterized by corneal edema, opacity, recurrent erosions and neovascularization. The delayed injuries were found in 25 and 40% of the eyes respectively, and when appearing, were more severe than the initial ones. CONCLUSIONS: The development of HD-induced ocular lesions in rabbits is similar to the lesions described in human casualties. Quantitative analysis of the various clinical parameters emphasizes the contribution of each tissue to the overall toxic picture. Our experimental model is useful for studying the pathological mechanisms of HD-ocular lesions, and may serve for testing potential therapies.
A strategy for increasing news media coverage of tobacco and health in Australia.
BACKGROUND: In many nations, government fiscal restraint is reducing the ability of public health authorities to mount mass-reach health information advertising campaigns. Strategies for increasing news coverage of health issues, and thereby contributing to policy advocacy, are well recognized, yet under-explored in health promotion research. OBJECTIVE: To increase news coverage of smoking and health issues by issuing media releases about research judged as newsworthy and important in contributing to tobacco control policy debates. METHOD: Research reports selected for their potential newsworthiness were promoted in news releases and their news 'hit rates' in New South Wales (Australia) metropolitan media over 5 weeks were compared with the background coverage of tobacco control issues over the same period. RESULTS: Fifty-eight of 283 (20.5%) news reports on tobacco in the study period were generated by the six media releases. CONCLUSIONS: News reportage of tobacco control and other public health issues can be increased significantly by the strategic use of news releases alerting journalists to research reports that embody recognizable news values. This is an inexpensive strategy with great potential to advance public health objectives.