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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 235 records · Page 13Linked to original sources

Drinking and driving in the United States: the 1996 National Roadside Survey.

Following the same general principles of its two predecessors in 1973 and 1986, the 1996 National Roadside Survey of weekend, nighttime drivers in the 48 contiguous states interviewed and breath tested over 6000 noncommercial four-wheel vehicle operators between September 6 and November 9, 1996. Results indicated that the total number of drinking drivers fell by about one-third between 1986 and 1996; however, there was no significant change in the number of drivers at blood alcohol concentrations (BACs) at or above 0.05. Compared to 1973, the proportion of women drivers on the roads during weekend nights has increased significantly. Moreover, relative to males, the proportion of female drivers who have been drinking has increased over the last decade. The number of drivers under the age of 21 with a BAC at or above 0.10 decreased significantly from 1986 to 1996.

Adult↗

Therapeutic landscapes in holistic medicine.

Therapeutic landscapes are places, settings, situations, locales, and milieus that encompass both the physical and psychological environments associated with treatment or healing, and the maintenance of health and well-being. Practices from holistic medicine--also known as nonconventional, alternative, complementary or traditional medicine--are used to illustrate specific humanistic concepts in further examining therapeutic landscapes. In addition to contributing to a theoretically-informed health geography, this paper further develops the concept of therapeutic landscapes and the understanding of holistic medicine.

Complementary Therapies↗

Pathogenicity in isolates of Salmonella enterica serotype Enteritidis PT4 which differ in RpoS expression: effects of growth phase and low temperature.

Experiments with 2 wild type isolates of Salmonella enterica serotype Enteritidis PT4, which differed in RpoS expression, tolerance to certain hostile environments and pathogenicity, found that changes in in vitro acid, heat, or peroxide tolerance had no effect on the ability of the isolates to multiply in the spleens of C57/BL7/J mice infected orally. Thus, with the pathogenic RpoS-positive isolate, the infectivity of log phase chilled cells, which are profoundly acid-sensitive, was the same as that of non-chilled stationary phase cells which are acid-tolerant. Similarity the infectivity of the RpoS-negative, sensitive isolate, was not enhanced by increases in any tolerance. The ability to survive on surfaces, like infectivity, was also largely unaffected by either growth phase or cold exposure. These two attributes may thus be related and, given that the pathogenic PT4 isolate is capable of prolonged survival and the nonpathogenic isolate survives poorly, survival could serve as a potential marker of pathogenicity. Although the pathogenicity of the two isolates was very different, they showed an almost identical increase in acid tolerance following culture at pH 4.0 for up to 60 min.

Acids↗

Isolation and characterization of two knotted-like homeobox genes from tomato.

Homeobox genes are known to play a role in developmental regulation. The knotted-like homeobox (knox) genes fall into two classes. The class I knox genes like knl, stml, and knatl are involved in maintaining meristem identity in cells. The function of class II knox genes is at yet undetermined. We have characterized two knox genes from tomato. LeT6 and LeT12 map to distinct chromosome locations that are different from the location for a recently cloned knox gene from tomato, tknl, confirming that plant homeobox genes are not clustered on chromosomes. These genes have a distinct expression pattern. Unlike other class I knl-like genes, LeT6 is expressed in developing lateral organs and developing ovaries in flowers. LeT12 is more ubiquitously expressed in the mature plant. RNA in situ localization data suggest that both these genes may have a role to play in formative events in ovule and embryo morphogenesis.

Amino Acid Sequence↗

In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell low-grade non-Hodgkin's lymphoma.

The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azumolene for the treatment of low-grade non-Hodgkin's lymphoma is warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Virus infection induces neuronal apoptosis: A comparison with trophic factor withdrawal.

Multicellular organisms can employ a number of defences to combat viral replication, the most dramatic being implementation of a cell autonomous apoptotic process. The overall cost to the viability of an organism of losing infected cells by apoptosis may be small if the dying cells can be substituted. In contrast, suicide of irreplaceable cells such as highly specialised neurons may have a more dramatic, even fatal consequence. Previous in vitro approaches to understanding whether neurotropic viruses cause neurons to apoptose have utilised transformed cell lines. These are not in the appropriate state of differentiation to provide an accurate indication of events in vivo. We have chosen to characterise the ability of a model CNS disease-causing virus, Semliki Forest virus (SFV), to infect and trigger apoptosis in primary cultures of nerve growth factor (NGF)-dependent sensory neurons. These cells are known to die when deprived of NGF and constitute a useful indicator of apoptosis. We observe that infection causes cell death which bears the morphological hallmarks of apoptosis, this occurs even in the present of survival promoting NGF and is concomitant with new virus production. Using the TUNEL (transferase dUTP nick end labelling) technique we show that SFV-induced apoptosis involves DNA fragmentation and requires caspase (CED-3/ICE cysteine protease) activation, as does apoptosis induced by NGF-deprivation. Extensive areas of apoptosis, as defined using a combination of ultrastructural analysis and TUNEL occur in infected neonatal mouse brains. The novel evidence that infection of primary neurons with SFV induces apoptosis with activation of one or more caspases defines a system for the further anlaysis of apoptosis regulation in physiologically relevant neurons.

Alphavirus Infections↗

Characteristics of new referrals to twenty-seven lymphoedema treatment units.

Lymphoedema affects 25-28% of patients who have undergone axillary surgery or radiotherapy in the treatment of cancer. The prevalence of primary lymphoedema or of lymphoedema secondary to non-cancer causes is unknown. In addition, basic demographic and disease characteristics of the lymphoedema population remain undocumented. We conducted a prospective survey to determine these characteristics. Lymphoedema treatment clinics in the UK were invited to participate at the British Lymphology Society 1996 Annual Conference. Twenty-seven clinics collected a standard data set for all new referrals in a 3-month period in 1997. The sample size was 603. The mean number of new referrals was 7.4 patients per unit per month. Eighty per cent of patients had cancer-related lymphoedema, and 86% of patients were female. Patients' mean age was 61.0 years. Thirty-seven per cent of the sample had suffered lymphoedema for less than 3 months, and 15% for 5 years or more. Patients with non-cancer related oedema had suffered the condition disproportionately longer than the cancer-related group (chi 2 = 102.2, P < 0.001). Sixty-six per cent of patients were reported as having lymphoedema at more than one site. Seventy-four per cent of all patients suffered unilateral limb oedema, and 23% bilateral limb oedema. Bilateral swelling was recorded for 67% of the non-cancer related group and 13% of the cancer related group (chi 2 = 153.4, P < 0.001). Median percentage excess volume (PCEV) for all patients with unilateral limb oedema was 16.4%. There was a positive relationship between PCEV and duration of the condition (H = 24.0, P < 0.001), and PCEV and non-cancer related lymphoedema (H = 10.5, P < 0.05). These results suggest that patients with non-cancer related lymphoedema and those with cancer-related lymphoedema form two distinct groups. The former present substantial management problems which are made more complex by late referral.

Adolescent↗

Suppression of elevated alanine aminotransferase activity in liver disease by vigabatrin.

A patient with hepatic cirrhosis due to Alpers disease is described who had a significantly raised plasma alanine aminotransferase (ALT) activity of 247 U/L which returned to normal (18 U/L) shortly after commencing treatment with the anticonvulsant drug, vigabatrin. Previous studies have reported smaller reductions in plasma ALT activity due to vigabatrin, generally in patients with normal liver function. This case demonstrates that vigabatrin may also reduce markedly elevated ALT activity to the normal range in patients with documented liver disease. Plasma ALT activity cannot be used as an index of liver cell damage in patients receiving vigabatrin.

Alanine Transaminase↗

Cognitive task analyses for decision centred design and training.

This paper presents three case studies of Cognitive Task Analysis (CTA) for defining systems design and training requirements. The approach taken involves a modification of the critical decision method of Klein et al. The authors utilized the revised CDM to obtain information from expert white-water rafting guides, general aviation pilots, and emergency ambulance dispatchers. The information obtained was used to develop multi-media tools for training rafting guides and general aviation pilots, and to redesign the VDU display requirements for the ambulance dispatchers. The examples demonstrate the utility of an approach to CTA that is closely based on relevant theory, and provides guidance to practitioners wishing to apply CTA techniques.

Adolescent↗

Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases.

Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in some JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease.

DNA-Binding Proteins↗

The Clinical Standards Advisory Group (CSAG) Cleft Lip and Palate Study.

A national study of care and outcomes in children born with a unilateral cleft lip and palate (UCLP) was performed over a 15-month period. Two cohorts of children ('5-year-olds' and '12-year-olds') were examined. There were 57 active cleft teams in the U.K. with 105 consultant orthodontists involved in the care of these children. Only 36 teams could provide basic data such as patients names. Of the patients, 47-51 per cent had neonatal appliances. The dental arch relationships were measured with the Goslon Index and a Five-Year-Old Index, 37-39 per cent of both age groups were either 'poor' or 'very poor'. Seventy per cent of the 12-year-old patients had a Skeletal III relation and 42 per cent of bone grafts were seriously deficient or failed. Dental treatment for active caries was needed by 40 per cent of 5-year-olds and 20 per cent of 12-year-olds. In addition, the training of recently appointed consultant orthodontists involved in the care of these children was scrutinized. As a whole, the results were disappointing with standards of care not significantly raised in the last decade. Recommendations have been made to the Department of Health and the implications for the orthodontic profession are explored. Overall, it seems that fewer orthodontists will need to be involved in a centralized care model for these children.

Bone Transplantation↗

Antioxidant defenses in lung lining fluid of broilers: impact of poor ventilation conditions.

Lung lining fluid antioxidants represent a potentially important protective barrier of lung epithelial cells to damaging effects of air pollutants, yet no information is apparently available concerning lung lining fluid antioxidants in broilers. Therefore, goals of this study were to establish uric acid, ascorbic acid, reduced (GSH) and oxidized (GSSG) glutathione, and protein concentrations in lung lining fluid obtained from male broiler chickens maintained for 6 to 7 wk within environmentally controlled rooms (Control) or chronically exposed to high levels of dust and ammonia within a broiler rearing house (House). The entire respiratory tract was carefully removed following an overdose of anesthetic and lavage fluid was collected after flushing the lungs with heparin-saline (10 mL per lung). There was no difference in GSH, but GSSG, uric acid, and protein concentrations were higher in House birds than in Controls. An increase in the GSSG to total glutathione (GSx) ratio, an indicator of oxidative stress, was also observed in birds maintained in the House environment. Ascorbic acid was not detected in House-reared birds and detected in only 4 of 12 Controls. Regression analysis revealed positive correlations between lung lining fluid protein and uric acid (r = 0.71; P < 0.01), protein and GSSG (r = 0.73; P < 0.01), and uric acid and GSSG concentrations (r = 0.69, P < 0.01). Additionally, GSSG was positively correlated (r = 0.66; P < 0.01) with the right ventricular weight ratio, an index commonly used in identifying the development of pulmonary hypertension syndrome in broilers. These data, the first to document lung lining fluid antioxidants in avian species, indicate an oxidative stress can be detected in fluid of broilers exposed to high levels of dust and ammonia in a simulated poultry house environment.

Animals↗

Cancer incidence and mortality around a hazardous waste depot.

The Castlereagh Regional Waste Disposal Depot (CRWDD) has been the focus of community concerns regarding the impact of hazardous waste disposal on their health and that of their local environment. As part of a phased epidemiological approach to investigate the levels of illness in people living in the vicinity of the CRWDD, routinely collected data were used to determine the rates of cancer and mortality in the area around the site and whether these rates were higher than expected when compared with New South Wales (NSW). The area investigated was based on eight census collection districts around the boundary of the CRWDD. Cancer incidence and mortality in the study area were calculated and compared to NSW using the indirect method of age and sex standardisation. Over an 18-year period, brain cancer in males (six cases) was the only cancer where the incidence in the study area was significantly higher than expected (SIR 380, 95% CL 139.4, 826.6). When this data were examined over smaller (arbitrary) time periods, there was an apparent cluster of brain cancer in males (three cases) between 1989 and 1991 (SIR 905, 95% CL 187,2646). There was a significant concentration of cases of cancers of the breast in females and cancers of the uterus over the smaller time periods. Although continued surveillance of these cancers is recommended, there are several basic limitations associated with small area data analysis that prevent a clear interpretation of these results. This limits our ability categorically to resolve the concerns of those living in the vicinity of the CRWDD.

Adult↗

Use of Mycobacterium tuberculosis complex-specific antigen cocktails for a skin test specific for tuberculosis.

The tuberculin skin test currently used to diagnose infection with Mycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.

Animals↗