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Biomedical subjects

D Bradshaw

Publications and source records attributed to D Bradshaw.

At least 19 recordsLinked to original sources
PubMed2005

Design, chirality, and flexibility in nanoporous molecule-based materials.

Scientific and technological interest in porous materials with molecule-sized channels and cavities has led to an intense search for controlled chemical routes to systems with specific properties. This Account details our work on directing the assembly of open-framework structures based on molecules and investigating how the response of nanoporous examples of such materials to guests differs from classical rigid porous systems. The stabilization of chiral nanoporosity by a hierarchy of interactions that both direct and maintain a helical open-framework structure exemplifies the approach.

Journal Article↗
PubMed2005

Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country.

BACKGROUND: As relatively little is known about adult wheeze and asthma in developing countries, this study aimed to determine the predictors of wheeze, asthma diagnosis, and current treatment in a national survey of South African adults. METHODS: A stratified national probability sample of households was drawn and all adults (>14 years) in the selected households were interviewed. Outcomes of interest were recent wheeze, asthma diagnosis, and current use of asthma medication. Predictors of interest were sex, age, household asset index, education, racial group, urban residence, medical insurance, domestic exposure to smoky fuels, occupational exposure, smoking, body mass index, and past tuberculosis. RESULTS: A total of 5671 men and 8155 women were studied. Although recent wheeze was reported by 14.4% of men and 17.6% of women and asthma diagnosis by 3.7% of men and 3.8% of women, women were less likely than men to be on current treatment (OR 0.6; 95% confidence interval (CI) 0.5 to 0.8). A history of tuberculosis was an independent predictor of both recent wheeze (OR 3.4; 95% CI 2.5 to 4.7) and asthma diagnosis (OR 2.2; 95% CI 1.5 to 3.2), as was occupational exposure (wheeze: OR 1.8; 95% CI 1.5 to 2.0; asthma diagnosis: OR 1.9; 95% CI 1.4 to 2.4). Smoking was associated with wheeze but not asthma diagnosis. Obesity showed an association with wheeze only in younger women. Both wheeze and asthma diagnosis were more prevalent in those with less education but had no association with the asset index. Independently, having medical insurance was associated with a higher prevalence of diagnosis. CONCLUSIONS: Some of the findings may be to due to reporting bias and heterogeneity of the categories wheeze and asthma diagnosis, which may overlap with post tuberculous airways obstruction and chronic obstructive pulmonary disease due to smoking and occupational exposures. The results underline the importance of controlling tuberculosis and occupational exposures as well as smoking in reducing chronic respiratory morbidity. Validation of the asthma questionnaire in this setting and research into the pathophysiology of post tuberculous airways obstruction are also needed.

Adolescent↗
PubMed2004

Tobacco attributable deaths in South Africa.

BACKGROUND: In mid 1998, a question "Was the deceased a smoker five years ago?" was introduced on the newly revised South African death notification form. DESIGN: A total of 16,230 new death notification forms from 1998 have been coded, and comparison of the prevalence of smoking among those who died of different causes was used to estimate, by case-control comparisons, tobacco attributed mortality in South Africa. Cases comprised deaths from causes known (from other studies) to be causally associated with smoking, and controls comprised deaths from medical conditions expected to be unrelated to smoking. Those who died from external causes, and from diseases strongly related to alcohol consumption, were excluded. SUBJECTS: Reports were available from 5340 deceased adults (age 25+), whose smoking status was given by a family member. RESULTS: Significantly increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0), other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart disease (OR 1.7, 95% CI 1.2 to 2.3). CONCLUSION: If smokers had the same death rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8% of all adult deaths in South Africa (more than 20 000 deaths a year) were caused by smoking.

Adult↗
PubMed2004

Predictors of chronic bronchitis in South African adults.

SETTING: National household survey of adults in South Africa, a middle income country. OBJECTIVE: To determine the prevalence and predictors of chronic bronchitis. DESIGN: A stratified national probability sample of households was selected. All adults in the selected households were interviewed. Chronic bronchitis was defined as chronic productive cough. Socio-demographic predictors were wealth, education, race, age and urban residence. Personal and exposure variables included history of tuberculosis, domestic exposure to smoky fuels, occupational exposures, smoking and body mass index. RESULTS: The overall prevalence of chronic bronchitis was 2.3% in men and 2.8% in women. The strongest predictor of chronic bronchitis was a history of tuberculosis (men, odds ratio [OR] 4.9; 95% confidence interval [CI] 2.6-9.2; women, OR 6.6; 95%CI 3.7-11.9). Other risk factors were smoking, occupational exposure (in men), domestic exposure to smoky fuel (in women) and (in univariate analysis only) being underweight. Wealth and particularly education were protective. CONCLUSION: The pattern of chronic bronchitis in South Africa suggests a combination of risk factors that includes not only smoking but also tuberculosis, occupational exposures in men and domestic fuel exposure in women. Control of these risk factors requires public health action across a broad front. The protective role of education requires elucidation.

Adolescent↗
PubMed2003

The influence of dehydration on the thermal preferences of the Western tiger snake, Notechis scutatus.

Temperature selection in tiger snakes (Notechis scutatus) is strongly influenced by hydration state and this response varies between two distinct neighbouring populations on semi-arid Carnac Island and mainland wetland (Herdsman Lake). Fed and hydrated (control) Carnac Island snakes selected a preferred body temperature of 26.2+/-1.2 degrees C and an average maximum temperature of 32.5+/-0.5 degrees C in a photo-thermal gradient. Dehydrated Carnac Island snakes selected a significantly lower preferred body temperature (19.7+/-1.6 degrees C) and average maximum temperature (27.7+/-1.0 degrees C). Control Herdsman Lake snakes selected a preferred body temperature of 27.5+/-0.6 degrees C and an average maximum temperature of 33.3+/-0.4 degrees C. Dehydrated Herdsman Lake snakes selected a significantly lower preferred body temperature (23.3+/-1.1 degrees C) and a lower average maximum temperature (31.8+/-0.6 degrees C). Thermal depression (decreased preferred body and average maximum temperatures) in response to dehydration was greater for Carnac Island than Herdsman Lake snakes. As decreases in temperature and activity can reduce water loss, our laboratory data suggest that the survival of the relict population of tiger snakes on Carnac Island is associated with thermoregulatory modifications, which may have the effect of enhancing water conservation in this waterless habitat.

Animals↗
PubMed2003

Seventeen novel HLA-A alleles.

This paper describes 17 novel HLA-A alleles: A*0244, A*0251, A*0254, A*0309, A*1111, A*2432, A*2434, A*2504, A*2618, A*2905, A*2906, A*3106, A*3107, A*3207, A*6820, A*7407, and A*7408. Most substitutions are found in other alleles.

Alleles↗
PubMed2003

Twenty-five novel HLA-B alleles.

Twenty-five novel HLA-B alleles are described in this paper: B*0729, B*1309, B*1814, B*1815, B*2724, B*2725, B*3539, B*3926, B*4037, B*4040, B*4042, B*4043, B*4044, B*4204, B*440203, B*4428, B*4429, B*4430, B*4505, B*5308, B*5309, B*5510, B*5511, B*570102, and B*5709. Most of the variants are single nucleotide substitutions. Two involve variants at the Bw4/Bw6 epitope. Two alleles carry substitutions of conserved amino acids.

Alleles↗
PubMed2003

Novel polymorphisms and the definition of promoter 'alleles' of the tumor necrosis factor and lymphotoxin alpha loci: inclusion in HLA haplotypes.

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) influence a variety of cellular responses and play a complex role in the immune response. Several single nucleotide polymorphisms (SNPs) have been reported in these major histocompatibility complex (MHC)-linked loci; however, a comprehensive examination of polymorphisms in the promoter regions of TNF and LTA has not been carried out and was undertaken here. Seven novel SNPs in LTA were identified by sequence analysis of 69 samples. Eight novel TNF alleles and 16 novel LTA alleles were designated. The TNF alleles clustered into two closely related groups, while the LTA alleles clustered into three distinct groups using phylogenetic and percentage difference analyses. A total of 52 unique TNF-LTA-HLA haplotypes are reported. There appear to be some associations between TNF/LTA alleles and HLA haplotypes, but not with specific HLA alleles. The majority of the SNPs appear to be randomly associated within and between the two loci except for the LTA SNPs at -293, +81 and +369. These observations may provide an explanation for the oftentimes contradictory results of studies associating individual cytokine gene SNPs with expression level phenotypes, HLA and disease.

Alleles↗
PubMed2003

Development of informatics tools for complex gene systems: killer-cell immunoglobulin-like receptor genes.

Killer-cell immunoglobulin-like receptors (KIRs) are a newly described family of polymorphic and highly homologous genes that have been difficult to classify and characterize. Before comprehensive analyzes of the genes are completed, researchers must struggle with completing the task of classifying and characterizing what is currently known. A collection and alignment of all KIR sequences found in GenBank was created to facilitate oligonucleotide reagent development and to provide an overall picture of this complex gene system. Two methods, a direct measurement of homology and phylogenetic analysis, were used to categorize sequences previously not specifically identified as belonging to a particular locus. The two methods agreed for 64.2% of sequences. A further 22.6% of uncategorized sequences were specified by only one method, although the assignments were consistent. Some sequences (11.3%) could not be assigned to a locus by either method. For one sequence, the two methods disagreed as to the locus assignment (1.9%). The failure to categorize a sequence was usually related to the short length of the sequence and the similarity among KIR loci. The tools developed in this study have been valuable in the analyses of KIR sequences and can be used for any complex gene system.

Base Sequence↗
PubMed2002

Novel HLA-A locus alleles including A*01012, A*0306, A*0308, A*2616, A*2617, A*3009, A*3206, A*3403, A*3602 and A*6604.

This paper describes 10 novel HLA-A alleles that have been characterized by DNA sequencing. Seven alleles, A*0308, A*2616, A*3009, A*3206, A*3403, A*3602 and A*6604 carry motifs observed in other HLA-A alleles, suggesting that gene conversion has created this diversity. The remaining three alleles, A*01012, A*0306 and A*2617, contain polymorphisms not previously found in any "classical" class I allele. All alleles were identified due to unexpected probe hybridization patterns during routine SSOP typing. Exons 2 and 3 of each allele were subsequently characterized by DNA sequencing.

Alleles↗
PubMed2002

(E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-alpha convertase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)-induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/- 0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14) of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg, i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro 32-7315-treated group, the reduced paw swelling was associated with improved lesion score and joint mobility. Furthermore, in a placebo-controlled, single-dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo, LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These data collectively support the potential use of such a compound for the oral treatment of inflammatory disorders.

ADAM Proteins↗
PubMed2002

Cognitive dysfunction after isolated brain stem insult. An underdiagnosed cause of long term morbidity.

Cognitive dysfunction adversely influences long term outcome after cerebral insult, but the potential for brain stem lesions to produce cognitive as well as physical impairments is not widely recognised. This report describes a series of seven consecutive patients referred to a neurological rehabilitation unit with lesions limited to brain stem structures, all of whom were shown to exhibit deficits in at least one domain of cognition. The practical importance of recognising cognitive dysfunction in this group of patients, and the theoretical significance of the disruption of specific cognitive domains by lesions to distributed neural circuits, are discussed.

Adult↗
PubMed2001

Changes in plasma progesterone in relation to vitellogenesis and gestation in the viviparous snake Vipera aspis.

Viviparity has arisen from oviparity on more than 100 independent occasions in squamate reptiles, providing an unique opportunity to investigate the ways in which endocrine control of gestation length has been modified by natural selection during this major transition in reproductive modes. Intuitively, the evolution of viviparity might be expected to involve an increasingly important role for the steroid hormone progesterone, rather than estradiol. Unfortunately, published data on this topic in snakes are scarce and often contradictory. Females of the viviparous snake Vipera aspis reproduce with a lower than annual frequency, providing the opportunity to examine steroid profiles simultaneously in vitellogenic, pregnant, and postparturient versus nonreproductive females. From 1990 to 1994, more than 500 blood samples were collected from more than 100 females. Progesterone, estradiol-17beta, and several plasma metabolites were assayed by radioimmunoassay and spectrophotometry. In contrast to earlier studies, we found significant differences between plasma progesterone levels in reproducing (10.5 +/- 9.1 ng ml(-1), N = 168) and nonreproducing (5.1 +/- 4.2 ng ml(-1), N = 121) females. Estradiol reached high levels during vitellogenesis (4.8 +/- 4.0 ng ml(-1), N = 16), and progesterone levels increased during gestation (from 3.7 ng ml(-1) before gestation to 18.7 ng ml(-1) at midgestation). However, experimental elevation of plasma progesterone levels with implants (up to 44.4 ng ml(-1)) did not modify plasma metabolite levels or delay parturition.

Animals↗