PubMed Health⌕ Search

Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 37 records · Page 2Linked to original sources

beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module.

Degeneration of neurons in Alzheimer's disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.

Alzheimer Disease↗

Modelling treated waste disposal in Port Phillip Bay and Bass Strait biogeochemical and physical removal.

Large cities, such as Melbourne, generate substantial quantities of sewage, which, after treatment, must be disposed. Melbourne's sewage is disposed via two routes, that treated at the Western Treatment Plant (WTP) is discharged in enclosed Port Phillip Bay, while the Boags Rock outfall empties into the exposed Bass Strait. In Port Phillip Bay biogeochemical processes control the fate of waste, while in the Bass Strait physical mixing rapidly disperses the waste. These different processes require very different ecosystem models. Port Phillip Bay requires detailed modelling of water-column and in-sediment processes, in particular detailed models of recycling processes, and also modelling of benthos-water-column interactions. Interaction of these components gives the model a nonlinear response to change in load. The Bass Strait ecosystem model is simple with no modelling of the sediment and limited modelling of water-column recycling. This model's behaviour is largely controlled by the physical environment.

Animals↗

Allelopathy, DIMBOA production and genetic variability in accessions of Triticum speltoides.

A screening was conducted to study the allelopathic potential of Australian-held accessions of Triticum speltoides. Of 26 accessions, four were found to inhibit root growth in the indicator species, lettuce (Lactuca sativa). The methanol leaf extracts of these accessions significantly reduced the root length of wild oat (Avena spp.). In all but one case, alellopathic accessions contained higher amounts of DIMBOA than did nonallelopathic accessions. Since some variation in allelopathic response was detected within lines, random amplified polymorphic DNA (RAPD) markers were used to estimate genetic diversity between and within the allelopathic accessions of Triticum speltoides L. The average genetic similarity between all possible pairs of selected accessions was found to be 55% and ranged from 44% to 88%. Comparison of DNA extracted from different single seedlings within the same accession revealed significant intraaccession genetic diversity (4-24%), although this was much less than that observed between accessions tested. This intraaccession diversity has significant implications for the selection of T. speltoides accessions in breeding or screening programs.

Benzoxazines↗

Habitual diet in four populations of African origin: a descriptive paper on nutrient intakes in rural and urban Cameroon, Jamaica and Caribbean migrants in Britain.

BACKGROUND: The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE: We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN: The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS: Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS: These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.

Adult↗

Reproducibility and validity of a quantitative food-frequency questionnaire among Jamaicans of African origin.

BACKGROUND: An interviewer-administered quantitative food-frequency questionnaire (FFQ) was developed to determine the energy and nutrient intakes of adult Jamaicans of African origin as part of a study of the epidemiology of diabetes and hypertension. METHODS: Reproducibility of the questionnaire was investigated in 123 participants aged 25-74 years. The relative validity of the FFQ was assessed against twelve 24-hour recalls administered over 12 months in 73 of the participants. In addition, energy intakes (EI) were compared with estimated basal metabolic rates (BMR). RESULTS: Reproducibility correlation coefficients (Pearson and intraclass) varied between 0.42 for retinol and 0.71 for carbohydrate, with most values falling between 0.50 and 0.60. When compared with repeated 24-hour recalls, the FFQ estimated slightly higher energy (mean 6%) and macronutrient intakes (mean 2-14%), and was within 5% when expressed as a percentage of energy intake. Micronutrients were higher by 1.19 (calcium) to 1.61 times (vitamin C). Unadjusted correlations between the FFQ and the reference method ranged from 0.20 for beta-carotene to 0.86 for alcohol. Cross-classification of nutrients into quartiles showed that 46-48% of participants in the lowest and highest quartiles were jointly classified by both methods. Misclassifications were low for most nutrients with one or two persons misclassified at the extreme quartiles. EI/BMR ratios suggested light to moderate activity levels appropriate for an urban population in a developing country. CONCLUSIONS: The FFQ showed reasonable reproducibility and validity and is suitable for estimating the habitual intakes of energy and macronutrients, but was poor for some micronutrients (retinol and beta-carotene).

Adult↗

Chest wall tenderness is unhelpful in the diagnosis of recurrent chest pain.

We investigated whether the presence of chest wall tenderness or fibromyalgia helped to distinguish between ischaemic and non-ischaemic chest pain. Seventy-one patients with recurrent chest pain, 36 with normal (group A) and 35 with abnormal coronary angiograms (group B), were assessed by investigator-administered questionnaires, and were examined for chest wall tenderness and fibromyalgia by a single blinded observer. Chest wall tenderness was greater in group A. However, it was much greater in women, who predominated in group A, than in men, who predominated in group B, and this explained the intergroup difference. Seven patients (25%) (six female, one male) in the group A and one patient (3%) (male) in group B (chi(2) p=0.027) fulfilled criteria for fibromyalgia. Patients with recurrent chest pain are more likely to have a ischaemic cause if they are male. Although our study suggests that chest wall tenderness alone in patients with recurrent chest pain has no value in excluding myocardial ischaemia as a cause, the confounding factor of gender prevents our study design from answering this question conclusively. Fibromyalgia is commoner in patients with chest pain and normal coronary angiograms, but may be related to the excess of females in this group. Its presence does not preclude the co-existence of ischaemic heart disease.

Angina Pectoris↗

No incremental benefit of multisite atrial pacing compared with right atrial pacing in patients with drug refractory paroxysmal atrial fibrillation.

OBJECTIVE: To evaluate the incremental antifibrillatory effect of multisite atrial pacing compared with right atrial pacing in patients with drug refractory paroxysmal atrial fibrillation paced for arrhythmia prevention alone. METHODS: In 20 of these patients (mean (SD) age 64 (8) years; 14 female, six male), a single blinded randomised crossover study was performed to investigate the incremental benefit of one month of multisite atrial pacing compared with one month of right atrial pacing. Outcomes included the number of episodes of paroxysmal atrial fibrillation, their total duration obtained from pacemaker Holter memory, and quality of life using a cardiac specific questionnaire (the modified Karolinska questionnaire). RESULTS: Comparing right atrial with multisite atrial pacing, there was no significant change in either the number of paroxysmal atrial fibrillation episodes (mean (SD): right atrial pacing 77 (98) episodes v multisite pacing 52 (78) episodes, NS) or their total duration (right atrial, 4.8 (5.4) days v multisite, 6.3 (9.8) days, NS). Quality of life scores compared with baseline status were equally improved by either pacing strategy (mean percentage improvement: right atrial, 38%, p = 0.003; multisite, 44%, p = 0.003). There was no significant difference in life scores comparing the two pacing modes. CONCLUSIONS: Multisite atrial pacing has no incremental antiarrhythmic effect compared with right atrial pacing in patients paced for drug refractory paroxysmal atrial fibrillation. Quality of life is equally improved with either pacing strategy, with no differences between them.

Aged↗

Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.

OBJECTIVE: To determine the importance of rhythm regulation or rate control in patients with permanent atrial fibrillation (AF) and normal left ventricular function. PATIENTS AND INTERVENTIONS: Thirty six patients with a mixed fast and slow ventricular response rate to their AF were randomised to either His bundle ablation (HBA) and VVIR pacemaker (HBA group) or VVI pacemaker and atrioventricular modifying drugs (Med group). Outcomes assessed at one, three, six, and 12 months included exercise duration and quality of life. RESULTS: Exercise duration significantly improved from baseline in both groups. There was no difference in outcome between the groups (Med +40% v HBA +20%, p = NS). The heart rate profile on exercise was similarly slowed in both groups compared to baseline. Quality of life significantly improved in both treatment arms for the modified Karolinska questionnaire (KQ) (Med +50% v HBA +50%, p = NS) and the Nottingham health profile (NHP) (Med +40% v HBA +20%, p = NS). However, for the individual symptom scores of each questionnaire more were improved in the Med group (KQ-Med 6 improved v HBA 4, NHP-Med 3 v HBA 1). Left ventricular function was equally preserved by both treatments during follow up. CONCLUSION: In these patients control of ventricular response rate with either HBA + VVIR pacemaker or atrioventricular modifying drugs + VVI pacemaker will lead to a significant improvement in exercise duration and quality of life. Rhythm regulation by HBA did not confer additional benefit, suggesting rate control alone is necessary for the successful symptomatic treatment of these patients in permanent AF.

Aged↗

Neurology in ancient faces.

BACKGROUND: Clinical paleoneurology is almost non-existent, but recognition of neurological diseases in ancient people might be possible by scrutinising portraits apparently representing people as they appeared in life. METHODS: About 200 mummy portraits painted in colour at the beginning of the first millennium were examined. Thirty two skulls excavated at Hawara in the Fayum (northern Egypt), where most of the portraits were found were measured, and nine caliper measures on each side of the skulls were taken. The right/left ratios were statistically analyzed by analysis of variance (ANOVA). One skull was subjected to 3D CT scanning and transilluminated. RESULTS: Two patients were found with progressive facial hemiatrophy (Parry-Romberg syndrome), three with deviations of the visual axes (tropia) and one with oval pupils (corectopia). CONCLUSIONS: Clinical paleoneurology is possible in the absence of a living nervous system. The patients probably had focal epilepsy, hemiplegic migraine, and autonomic nervous system dysfunction.

Facial Asymmetry↗

Unexplained groin pain: safety and reliability of herniography for the diagnosis of occult hernias.

A retrospective study of our initial experience of herniography in a district general hospital is presented. A total of 43 herniograms were performed in 41 patients (median age 57, range 16-77, 27 males, 14 females) over a two year period. Four herniograms were unsuccessful due to failed intraperitoneal contrast injection, of which two were repeated (success rate 90.5%). A total of 25 groin hernias were identified radiologically (two on the asymptomatic side). Twenty one patients underwent surgery and a hernia was confirmed in 19 (true positive rate 90.5%). Sixteen herniograms were considered negative and after a median follow up of 28 months (range 16-42 months), none of these patients have developed a hernia. There were no major complications. It is concluded that herniography is a safe and reliable method of determining or excluding the presence of an occult groin hernia.

Adolescent↗

Developing child and adolescent mental health services.

Twenty four projects nationwide received government funding to improve child mental health services. These initiatives are expected to deliver innovative changes and enhanced interprofessional working. This preliminary evaluation in Norfolk suggests early intervention can offer acceptable, accessible, and appropriate support for children and families.

Adolescent↗

E. Coli MurG: a paradigm for a superfamily of glycosyltransferases.

MurG is an essential bacterial glycosyltransferase that is involved in the biosynthesis of peptidoglycan. The enzyme is found in all organisms that synthesize peptidoglycan and is a target for the design of new antibiotics. A direct assay to study MurG was reported recently, followed shortly by the crystal structure of E. coli MurG. This first MurG structure, combined with sequence data on other glycosyltransferases, has revealed that MurG is a paradigm for a large family of metal ion-independent glycosyltransferases found in both eukaryotes and prokaryotes. A better understanding of MurG could lead to the development of new drugs to combat antibiotic resistant infections, and may also shed light on a broad class of glycosyltransferases.

Amino Acid Sequence↗

Evidence-based dentistry: Part III. Searching for answers to clinical questions: finding evidence on the Internet.

The Internet is rapidly becoming a valuable source of information for all health care professionals, as well as for the consumers of health care--patients and their families and friends. Information on the Internet is uncontrolled and generally unevaluated. The quality filter of peer review, present in published dental journals, is usually lacking in Internet-based health sources. There are, however, a number of well-developed, highly-credible and useful resources available online that provide evidence-based information. In this paper, the third in a 6-part series on evidence-based practice, we discuss some of the sites that we have found to be most helpful for learning, teaching and practising evidence-based care.

Clinical Trials as Topic↗

The effects of sublingual glyceryl trinitrate on walking distance in patients with intermittent claudication. A randomised, doubled-blind, placebo-controlled, cross-over study.

BACKGROUND: Intermittent claudication (IC) is a common problem in older age. New work shows that the administration of glyceryl trinitrate (GTN) can reduce the fall in ankle brachial pressure index (ABPI) after exercise and can increase maximum walking distance by 19% on treadmill exercise. The aim of this study was to further define the clinical benefits of GTN in patients with PVD. METHODS: The study is of a randomised, double-blind, placebo-controlled cross-over design. We studied 29 patients with intermittent claudication where the median age was 67.5 years (45-84). This included 20 males and nine females, and six of these patients were diabetics. To be selected, the patients had to have a history of IC with a resting ABPI of 1.0 or less, that fell by more than 0.1 on exercise. Patients were walked for 15 min on flat ground following GTN spray or placebo and total distances walked were measured. This was then followed by the crossover component of the trial. RESULTS: Median walking distance with placebo was 825 m (100-1300 m) and with GTN was 900 m (240-1400 m). This is an increase of 9% (p = 0.02, using the Wilcoxon matched pairs signed ranks test). CONCLUSION: This study shows a statistically significant improvement in walking distance with GTN in patients with IC.

Administration, Sublingual↗

Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm.

BACKGROUND: We have developed a transgenic mouse with cardiac-restricted overexpression of tumor necrosis factor-alpha (TNF-alpha). These mice develop a heart failure phenotype characterized by left ventricular dysfunction and remodeling, pulmonary edema, and elevated levels of TNF-alpha in the peripheral circulation from cardiac spillover. Given that TNF-alpha causes atrophy and loss of function in respiratory muscle, we asked whether transgenic mice developed diaphragm dysfunction and whether contractile losses were caused by oxidative stress or tissue remodeling. METHODS AND RESULTS: muscles excised from transgenic mice and littermate controls were studied in vitro with direct electrical stimulation. Cytosolic oxidant levels were measured with 2', 7'-dichlorofluorescin diacetate; emissions of the oxidized product were detected by fluorescence microscopy. Force generation by the diaphragm of transgenic animals was 47% less than control (13.2+/-0. 8 [+/-SEM] versus 25.1+/-0.6 N/cm(2); P:<0.001); this weakness was associated with greater intracellular oxidant levels (P:<0.025) and was partially reversed by 30-minute incubation with the antioxidant N:-acetylcysteine 10 mmol/L (P:<0.01). Exogenous TNF-alpha 500 micromol/L increased oxidant production in diaphragm of wild-type mice and caused weakness that was inhibited by N:-acetylcysteine, suggesting that changes observed in the diaphragm of transgenic animals were mediated by TNF-alpha. There were no differences in body or diaphragm weights between transgenic and control animals, nor was there evidence of muscle injury or apoptosis. CONCLUSIONS: Elevated circulating levels of TNF-alpha provoke contractile dysfunction in the diaphragm through an endocrine mechanism thought to be mediated by oxidative stress.

Animals↗