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A Davison

Publications and source records attributed to A Davison.

At least 19 recordsLinked to original sources

The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women.

We studied the association between plasma total homocysteine (tHcy), its determinants folate, vitamin B(12), vitamin B(6) and MTHFR genotype, and bone mineral density (BMD) in 328 postmenopausal British women. When the subjects were assigned to one of 3 groups (control, osteopenic or osteoporotic) according to their BMD at the os calcis, those in the osteoporotic group had, compared with the controls, a significantly lower serum folate concentration, a significantly higher % of current smokers and a significantly higher incidence of recent fracture. In the population as a whole, we found significant associations of BMD with tHcy (r=-0.130, p=0.033, log tHcy) and folate (r=0.132, p=0.025, log folate). The association of folate with BMD was maintained after correction for age, weight and height (r=0.124, p=0.042, log folate), but the association of tHcy with BMD weakened after correction for age, weight, height and creatinine (r=-0.117, p=0.059, log tHcy). Vitamins B(12) and B(6) were not associated with BMD, but were significantly associated with tHcy, vitamin B(12) (r=-0.34, p<0.0001), vitamin B(6) (r=-0.16, p=0.007), as was folate (r=-0.41, p<0.0001). There was an increasing frequency of the MTHFR TT genotype across the 3 BMD groups, but this did not attain significance. Individuals with the TT genotype had significantly higher plasma tHcy but there was no difference between the genotypes (CC, CT, TT) for folate or BMD. Smoking was associated with a highly significant reduction in BMD and lower weight, and a significant reduction in circulating folate and vitamin B(6) concentrations, but no change in tHcy or vitamin B(12) concentrations when compared with non-smokers. We conclude that low serum folate is a significant risk factor for osteoporosis, with plasma tHcy having a lesser effect. Both vitamins B(12) and B(6), by acting through tHcy, may also have an effect on the skeleton, albeit a weaker one than folate. Cigarette smoking is a strong determinant of BMD, and may act through effects on folate and vitamin B(6).

Aged↗

The convoluted evolution of snail chirality.

The direction that a snail (Mollusca: Gastropoda) coils, whether dextral (right-handed) or sinistral (left-handed), originates in early development but is most easily observed in the shell form of the adult. Here, we review recent progress in understanding snail chirality from genetic, developmental and ecological perspectives. In the few species that have been characterized, chirality is determined by a single genetic locus with delayed inheritance, which means that the genotype is expressed in the mother's offspring. Although research lags behind the studies of asymmetry in the mouse and nematode, attempts to isolate the loci involved in snail chirality have begun, with the final aim of understanding how the axis of left-right asymmetry is established. In nature, most snail taxa (>90%) are dextral, but sinistrality is known from mutant individuals, populations within dextral species, entirely sinistral species, genera and even families. Ordinarily, it is expected that strong frequency-dependent selection should act against the establishment of new chiral types because the chiral minority have difficulty finding a suitable mating partner (their genitalia are on the 'wrong' side). Mixed populations should therefore not persist. Intriguingly, however, a very few land snail species, notably the subgenus Amphidromus sensu stricto, not only appear to mate randomly between different chiral types, but also have a stable, within-population chiral dimorphism, which suggests the involvement of a balancing factor. At the other end of the spectrum, in many species, different chiral types are unable to mate and so could be reproductively isolated from one another. However, while empirical data, models and simulations have indicated that chiral reversal must sometimes occur, it is rarely likely to lead to so-called 'single-gene' speciation. Nevertheless, chiral reversal could still be a contributing factor to speciation (or to divergence after speciation) when reproductive character displacement is involved. Understanding the establishment of chirality, the preponderance of dextral species and the rare instances of stable dimorphism is an important target for future research. Since the genetics of chirality have been studied in only a few pulmonate species, we also urge that more taxa, especially those from the sea, should be investigated.

Animal Structures↗

An expressed sequence tag survey of gene expression in the pond snail Lymnaea stagnalis, an intermediate vector of trematodes [corrected].

The pond snail Lymnaea stagnalis is an intermediate vector for the liver fluke Fasciola hepatica, a common parasite of ruminants and humans. Yet, despite being a disease of medical and economic importance, as well as a potentially useful comparative tool, the genetics of the relationship between Lymnaea and Fasciola has barely been investigated. As a complement to forthcoming F. hepatica expressed sequence tags (ESTs), we generated 1320 ESTs from L. stagnalis central nervous system (CNS) libraries. We estimate that these sequences derive from 771 different genes, of which 374 showed significant similarity to proteins in public databases, and 169 were similar to ESTs from the snail vector Biomphalaria glabrata. These L. stagnalis ESTs will provide insight into the function of the snail CNS, as well as the molecular components of behaviour and response to parasitism. In the future, the comparative analysis of Lymnaea/Fasciola with Biomphalaria/Schistosoma will help to understand both conserved and divergent aspects of the host-parasite relationship. The L. stagnalis ESTs will also assist gene prediction in the forthcoming B. glabrata genome sequence. The dataset is available for searching on the world-wide web at http://zeldia.cap.ed.ac.uk/mollusca.html.

Amino Acid Sequence↗

Conservation genetics and population history of the threatened European mink Mustela lutreola, with an emphasis on the west European population.

In species of great conservation concern, special attention must be paid to their phylogeography, in particular the origin of animals for captive breeding and reintroduction. The endangered European mink lives now in at least three well-separated populations in northeast, southeast and west Europe. Our aim is to assess the genetic structure of these populations to identify 'distinct population segments' (DPS) and advise captive breeding programmes. First, the mtDNA control region was completely sequenced in 176 minks and 10 polecats. The analysis revealed that the western population is characterized by a single mtDNA haplotype that is closely related to those in eastern regions but nevertheless, not found there to date. The northeast European animals are much more variable (pi = 0.012, h = 0.939), with the southeast samples intermediate (pi = 0.0012, h = 0.469). Second, 155 European mink were genotyped using six microsatellites. The latter display the same trends of genetic diversity among regions as mtDNA [gene diversity and allelic richness highest in northeast Europe (H(E) = 0.539, R(S) = 3.76), lowest in west Europe (H(E) = 0.379, R(S) = 2.12)], and provide evidences that the southeast and possibly the west populations have undergone a recent bottleneck. Our results indicate that the western population derives from a few animals which recently colonized this region, possibly after a human introduction. Microsatellite data also reveal that isolation by distance occurs in the western population, causing some inbreeding because related individuals mate. As genetic data indicate that the three populations have not undergone independent evolutionary histories for long (no phylogeographical structure), they should not be considered as distinct DPS. In conclusion, the captive breeding programme should use animals from different parts of the species' present distribution area.

Animals↗

Historical demography of Mullerian mimicry in the neotropical Heliconius butterflies.

We compare the historical demographies of two Müllerian comimetic butterfly species: Heliconius erato and Heliconius melpomene. These species show an extensive parallel geographic divergence in their aposematic wing phenotypes. Recent studies suggest that this coincident mosaic results from simultaneous demographic processes shaped by extrinsic forces over Pleistocene climate fluctuations. However, DNA sequence variation at two rapidly evolving unlinked nuclear loci, Mannose phosphate isomerase (Mpi) and Triose phosphate isomerase (Tpi), show that the comimetic species have quite different quaternary demographies. In H. erato, despite ongoing lineage sorting across the Andes, nuclear genealogical estimates showed little geographical structure, suggesting high historical gene flow. Coalescent-based demographic analysis revealed population growth since the Pliocene period. Although these patterns suggest vicariant population subdivision associated with the Andean orogeny, they are not consistent with hypotheses of Pleistocene population fragmentation facilitating allopatric wing phenotype radiation in H. erato. In contrast, nuclear genetic diversity, theta, in H. melpomene was reduced relative to its comimic and revealed three phylogeographical clades. The pattern of coalescent events within regional clades was most consistent with population growth in relatively isolated populations after a recent period of restricted population size. These different demographic histories suggest that the wing-pattern radiations were not coincident in the two species. Instead, larger effective population size (N(e)) in H. erato, together with profound population change in H. melpomene, supports an earlier hypothesis that H. erato diversified first as the model species of this remarkable mimetic association.

Alleles↗

The proliferative effects of 5-androstene-3 beta,17 beta-diol and 5 alpha-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines.

Epidemiological studies suggest that precursor steroids are implicated in the aetiology of breast cancer. However, our understanding of the role of precursor steroids in breast cancer is complicated by fact that there are many precursor steroids, which are metabolically inter-related and have divergent proliferative activities on the growth of breast cancer cell lines. In this study the proliferative affects of 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol, which may be considered true metabolites acting at a tissue level, on MCF7, T47D and MDAMB231 breast cancer cell lines have been examined by a flow cytometric technique. DNA cell cycle analysis demonstrates that 5-androstene-3 beta,17 beta-diol stimulates the proliferation of hormone-dependent cell lines at physiological levels by an oestrogen receptor mediated mechanism whereas 5 alpha-dihydrotestosterone does not affect the proliferation of MCF7 and T47D cell lines at physiological levels over short (48 h) incubations. Both 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol stimulate proliferation of hormone-dependent cell lines at pharmacological levels via and interaction with the oestrogen receptor. In long (6-9 days) incubations both 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol inhibit the 17 beta-oestradiol induced proliferation of MCF7 and T47D cell lines, however, 5 alpha-dihydrotestosterone inhibits while 5-androstene-3 beta,17 beta-diol stimulates basal proliferation. These cell line studies suggest a model for the role of precursor steroids in pre- and postmenopausal breast cancer.

Anabolic Agents↗

Awareness of swimming pool suction injury among tour operators.

A 6 year old girl suffered rectal prolapse after being sucked onto a swimming pool drain from which the cover had been removed. After six days in hospital she made a full recovery. The severe form of this injury may result in evisceration of small bowel, short bowel syndrome, and the need for long term parenteral nutrition. A survey of travel agents revealed a low awareness of this potentially devastating hazard, and a failure on the part of some companies to take adequate responsibility for customer safety. Preventive measures are reviewed.

Accidents↗

Integrated water cycle planning for towns in New South Wales, Australia.

Integration means different things to different people and as a consequence appears to only partially deliver on promised outcomes. For effective integrated water cycle management these outcomes should include improved water use efficiency, less waste, environmental sustainability, and provide secure and reliable supply to meet social and economic needs. The objective of integration is the management and combination of all these outcomes as part of a whole, so as to provide better outcomes than would be expected by managing the parts independently. Integration is also a consequence of the Water Reforms embarked on by the NSW State Government in 1995. The key goals of the reforms are clean and healthy rivers and groundwaters, and the establishment of more secure water entitlements for users. They are also essential for meeting the Council of Australian Government (COAG) water management strategies. The policies and guidelines that formed the NSW Water Reforms were the basis of the Water Management Act 2000 (NSW) (WMA) which is the legislative framework for water management in NSW. The NSW Department of Land and Water Conservation has developed an approach to integrated water cycle management for rural centres in NSW based on a catchment and policy context. This approach includes consideration of catchment wide needs and issues, environmental sustainability, government policy and community objectives in the development of an integrated water cycle plan. The approach provides for a transparent assessment of priorities and how to deal with them, and while specific to urban centres, could easily be expanded for use in the management of the whole of the catchment water cycle. Integration of the water cycle is expected to offer benefits to the local environment, community and economy. For instance, any unused proportion of an urban centre's water entitlement, or an offset against this entitlement created through returned flows (such as via good quality sewage effluent discharge to a river), can provide a surplus which is available to be traded on an annual basis. Further, improved demand management within an urban centre can be expected to result in a reduction in abstraction against the licence entitlement. This may result in the increased availability of in-stream water for environmental or other purposes and is expected to increase the economic value of returned water. Improved water use efficiencies are also expected to result in reduced capital works (and their associated costs) as the efficiency of service delivery and resource use improves. In this paper an example of the application of this process is provided and the outcomes discussed.

Conservation of Natural Resources↗

[99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma.

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.

Animals↗

Mitochondrial phylogeography and population history of pine martens Martes martes compared with polecats Mustela putorius.

The flora and fauna of Europe are linked by a common biogeographic history, most recently the Pleistocene glaciations that restricted the range of most species to southern refugial populations. Changes in population size and migration, as well as selection, have all left a signature on the genetic differentiation. Thus, three paradigms of postglacial recolonization have been described, inferred from the patterns of DNA differentiation. Yet some species, especially wide-ranging carnivores, exhibit little population structuring between the proposed refugia, although relatively few have been studied due to the difficulty of obtaining samples. Therefore, we investigated mitochondrial variation in pine martens, Martes martes, in order to understand the extent to which they were affected by glacial cycles, and compared the results with an analysis of sequences from polecats, Mustela putorius. A general lack of ancient lineages, and a mismatch distribution that is consistent with an expanding population, is evidence that the present-day M. martes and Mu. putorius in central and northern Europe colonized from a single European refugium following a recent glaciation. There has also been interspecific mitochondrial introgression between M. martes and the sable M. zibellina in Fennoscandia.

Amino Acid Substitution↗

Directional dependence in film dosimetry: radiographic and radiochromic film.

The trend towards conformal, intensity modulated radiotherapy treatments has established the need for a true integrating dosimeter. In traditional radiotherapy, radiographic film dosimetry is commonly used. The accuracy and reproducibility of film optical density as an indicator of dose is influenced by several variables, including the chemical processing conditions. As a result radiochromic film, with all the advantages of radiographic film but without the need for chemical processing, has increased in popularity, although the low-dose sensitivity of radiochromic film does remain a disadvantage for some experiments. Several studies have investigated the reproducibility of radiochromic film results, but none have specifically addressed the well-known directional dependence seen with traditional radiographic film. In this study, the directional dependence of radiographic (Kodak X-omat V) and radiochromic (Gafchromic) films were measured. It was found that both films over responded when exposed parallel to the central axis of the beam as opposed to perpendicular exposure. An attempt is made to explain the reason for the responses of both films in terms of spectral effects and the air gap between the phantom segments. Although radiographic film exposed parallel rather than perpendicular to the central axis of the beam exhibits a measured difference in film response at depth, this over response does not occur when the extent of the film is restricted to a small region at the centre of the phantom (in this case an air gap is not introduced across the phantom). This suggests that it is the air gap rather than the orientation of the film that is the cause of the over response. Furthermore, when film occupies a slice through the entire phantom an over response occurs for both radiographic and radiochromic film, indicating that spectral effects are not the cause.

Film Dosimetry↗

History or current selection? A molecular analysis of 'area effects' in the land snail Cepaea nemoralis.

We have used molecular variation in microsatellite and mitochondrial DNA to throw light on the origins of enigmatic geographical patterns, known as 'area effects', in the shell polymorphisms of the land snail Cepaea nemoralis. Our aim was to assess the relative importance of recent selection and historical events in the formation of these patterns. On the Marlborough Downs in Wiltshire, England, the 'type locality' for area effects, the frequencies of microsatellites are significantly associated with the frequencies of alleles for shell banding. A less clear association is found between microsatellites and shell colour. Mitochondrial haplotypes show no significant relationships. Although the correlated geographical patterns could be the results of random genetic drift from an initially uniform array of populations, the magnitudes of the patterns, and of the correlations between them, seem too strong to have arisen by drift since the last glaciation. Our results suggest that invasions from refugia have been the most important factors in forming area effects.

Animals↗

'3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma: synthesis and evaluation in vitro and in vivo.

'3+1' Mixed-ligand [(99m)Tc]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et(2)N(CH(2))(2)] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn(2+) as the reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX(2))] in high radiochemical yield (60-98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1-6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.

Animals↗

Correlation between autopsy findings for chronic obstructive airways disease and in-life disability in South African gold miners.

OBJECTIVES: In South Africa chronic obstructive airway disease (COAD), which could be due to working in a dusty atmosphere in scheduled mines or works, is a compensatable disease. Miners are compensated for in-life respiratory disability and for findings at autopsy of COAD, which includes emphysema, bronchitis assessed by mucus gland hyperplasia in the main bronchus, and bronchiolitis assessed by goblet cell metaplasia. The question arises as to whether the autopsy findings correlate with in-life impairment. The objectives of the study were: (1) to determine whether autopsy COAD outcomes relate to lung function and to respiratory symptoms and signs; and (2) to quantify the individual contributions of emphysema, bronchiolitis and bronchitis to lung function impairment. METHODS: On 724 gold miners, pathological findings of COAD--emphysema, bronchitis and bronchiolitis-- were related to lung function measurements and respiratory symptoms and signs observed within 5 years prior to death. RESULTS: Emphysema diagnosed at autopsy was the main determinant of airflow impairment. The emphysema score categories 0-5, 5-35, 35-65 and > 65 were associated with decreased forced expiratory volume in 1 s, expressed as percentage predicted (FEV1%) as follows: 78.8%, 66.2%, 52.0% and 46.0%, respectively. The score was also associated with increasing frequency of dyspnoea. After adjustment for emphysema, the bronchitis and bronchiolitis were not related to significant lung function loss, and in subjects without emphysema, the presence of moderate or marked bronchitis was associated with a mild impairment only. Bronchitis at autopsy was associated with increased frequency of rhonchi, sputum and cough, whereas bronchiolitis was associated with increased sputum only. Silicosis found at autopsy was associated with some obstructive and restrictive lung function impairment. Tobacco smoking was associated with all the COAD outcomes.

Aged↗

Ultrasonic fetal measurements: new Australian standards for the new millennium.

In over 30 years of ultrasound assessment of the fetus, Australian researchers have only produced growth curves for the biparietal diameter (BPD) and occipito-frontal diameter (OFD) for general use. The overseas curves used for other fetal parameters are up to 25 years old and based on predominantly white middle class sample populations. In the last decade the ethnicity in Australia has changed significantly, putting into question the accuracy of the existing charts. This 3-year study of 3,800 pregnancies has resulted in the production of fetal measurement charts for the BPD, OFD, head circumference (HC), abdominal circumference (AC), crown rump length (CRL), femur and humerus lengths. Using over 11,600 measurements collected from diverse ethnic, social and economic groups within the Australian population, rigorous statistical analysis was performed. The results showed that statistically significant differences occur between the curves currently in regular use and those for the OFD, HC, AC, CRL and humerus length obtained from our data.

Abdomen↗

"What do you think about genetic medicine?" Facilitating sociable public discourse on developments in the new genetics.

An important aspect of any meaningful public discussion about developments in gene technology is the provision of opportunities for interested publics to engage in sociable public discourse with other lay people and with experts. This article reports on a series of peer group conversations conducted in late 1996 and early 1997 with sixteen community groups in Perth, Western Australia, interested in gene therapy technology. With the case of cystic fibrosis as a particular focus, and using background resource material as a stimulus for discussion, the participating groups explored a range of value issues arising from the new genetic medicine. This more discursive context enabled participants to express a number of background or life-world concerns about genetic medicine, concerns that are often obscured by the dominant biomedical and bioethical discourses.

Attitude↗