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Biomedical subjects

L Hayes

Publications and source records attributed to L Hayes.

At least 19 recordsLinked to original sources
PubMed2006

Lifecourse predictors of normal metabolic parameters in overweight and obese adults.

OBJECTIVE: Not all overweight and obese individuals appear to be at equal risk of developing metabolic abnormalities. We sought to examine the effect of factors from different stages of life on risk of metabolic abnormalities at age 50 years in overweight and obese adults. DESIGN AND SUBJECTS: Longitudinal study of all persons born in Newcastle upon Tyne, UK in May and June 1947 and followed to age 50 years when a clinical examination took place and a detailed questionnaire on health and lifestyle was completed. Participants in this study (n=223) were those defined as being overweight or obese with a body mass index (BMI) greater than or equal to 25 at age 50 years. Subjects were defined as 'metabolically normal' if they had normal lipids, glucose and blood pressure. RESULTS: Lower BMI was the strongest predictor of remaining metabolically normal in both men and women. After adjusting for BMI, lower levels of cigarette smoking and higher levels of physical activity were independently associated with being metabolically normal in men. No other factors were independently associated with being metabolically normal in women. A stronger inverse relationship between BMI and metabolic status was found in men (Odds ratio (OR) per unit increase in BMI=0.65, 95% confidence intervals (95% CI) 0.52-0.81) than in women (OR=0.90, 95% CI 0.82-0.99). No association was seen for factors operating in fetal, infant and childhood life. CONCLUSIONS: Adult factors made a greater contribution to remaining metabolically normal than birth or childhood factors in this sample of overweight and obese adults. A lower adult BMI appeared to reduce the risk in men and women and lower cigarette smoking and higher level of physical activity also independently reduced the risk in men. Public health policy to reduce the burden of morbidity associated with obesity should continue to encourage weight loss, physical activity and smoking cessation.

Body Constitution↗
PubMed2002

Identification of a novel mutation in Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis.

We report a new missense mutation (Ala140Gly) in exon 5 of the Cu/Zn superoxide dismutase (SOD-1) gene in a 73-year-old man with familial amyotrophic lateral sclerosis (FALS). The enzymatic activity of mutated SOD-1 measured in erythrocyte lysate was 70% of control. This heterozygote mutation, which is associated with the late onset of the disease, is located in the active site of the enzyme.

Aged↗
PubMed2002

Pharmacogenomic analysis of rhIL-11 treatment in the HLA-B27 rat model of inflammatory bowel disease.

Recombinant human interleukin-11 (rhIL-11) reduces the clinical signs and histological lesions of inflammatory bowel disease (IBD) in transgenic rats expressing the human major histocompatability complex (MHC) class I allele, HLA-B27. To elucidate the pharmacogenomic effects of rhIL-11 in this model, we examined the global gene expression pattern in inflamed colonic tissue before and following rhIL-11 treatment using oligonucleotide microarrays. In total, 175 disease-related genes were identified. Increased expression of genes involved in antigen presentation, cell death and inflammation, and decreased expression of metabolic genes was associated with disease. A total of 27 disease-related genes returned to normal expression levels following rhIL-11 treatment including the MHC class II gene RT1-DMbeta. rhIL-11 induced the expression of four intestinal epithelial growth factors. These gene expression patterns indicate that treatment of inflammatory bowel disease with rhIL-11 affects class II antigen processing and colonic epithelial cell proliferation and metabolism.

Animals↗
PubMed2002

Distinct phenotypic adhesion molecule expression on human cord blood progenitors during early Eosinophilic commitment: upregulation of beta(7) integrins.

Increasing levels of proinflammatory cells, including eosinophils and basophils, are seen at the site of allergen challenge in allergic disease of the airways. Mechanisms for the recruitment of these cell types could involve either specific upregulation of adhesion molecule and chemoattraction, or the initiation of proliferation and differentiation of inflammatory cell progenitors derived from the bone marrow. In this study, we demonstrate, in two systems of eosinophilic-basophilic lineage-committed granulocytes of relative immaturity, that eosinophilic differentiation in vivo implies the induction of a distinct adhesion phenotype, characterized by the upregulation of beta(7) integrin and downregulation of beta(1) and alpha(5) integrins. Moreover, the eosinophilic differentiation induced an upregulation of complement receptor type 1 and type 3, and the expression was further enhanced upon a short-course in vitro activation with ionomycin. These data indicate a sequential alteration of disparate members of the integrin family during eosinophilic-basophilic differentiation, which may attribute to specific adhesion requirements at distinct stages of cell maturation.

Antigens, CD↗
PubMed2002

Evaluating the cost and efficacy of leg ulcer care provided in two large UK health authorities.

OBJECTIVE: This prospective study investigated the cost and efficacy of leg ulcer care over a three-month period during 1993, 1994 and 1999. It compared two health authorities (Stockport and Trafford) whose populations totalled 540,000. METHOD: All patients with active leg ulcers were invited to community leg ulcer clinics offering research-based innovations in care. Patients without significant arterial disease (ankle brachial pressure index less than 0.8) were treated with multilayer compression bandaging. RESULTS: The 42% healing rate reported in the original Stockport study was maintained at 40% in 1999, although the 65% healing rate achieved by the leg ulcer clinics in 1993 was not replicated, with rates falling to 46%. Following the opening of community leg ulcer clinics in Trafford, healing rates rose from 20% to 42%. The annual expenditure on leg ulcer care in Stockport increased from 65,545.56 Pounds to 83,344.30 Pounds, while in Trafford the cost of care dropped from 151,375.35 Pounds to 53,176.76 Pounds between 1994 and 1999. CONCLUSION: This study suggests that reductions in costs and improvements in healing rates can be sustained in a mature community leg ulcer clinic programme staffed by specialist leg ulcer nurses.

Aged↗
PubMed2001

Noncommunicable diseases in sub-Saharan Africa: where do they feature in the health research agenda?

There is no doubt that communicable diseases will remain the predominant health problem for the populations in sub-Saharan Africa, including adults, for the next 10-20 years. Concern has been expressed that the available resources to deal with this problem would be reduced by increasing the emphasis on noncommunicable diseases. The latter, however, already present a substantial burden because their overall age-specific rates are currently higher in adults in sub-Saharan Africa than in populations in Established Market Economies. There is also evidence that the prevalence of certain noncommunicable diseases, such as diabetes and hypertension, is increasing rapidly, particularly in the urban areas, and that significant demands are being made on the health services by patients with these diseases. To ignore the noncommunicable diseases would inevitably lead to an increase in their burden; the provision of health services for them would be largely undirected by issues of clinical and cost effectiveness, and their treatment and prevention would be left to the mercy of local and global commercial interests. Improved surveillance of all diseases within sub-Saharan Africa is needed in order to place noncommunicable diseases properly within the context of the overall burden of disease. Research is needed to guide improvements in the clinical and cost effectiveness of resources currently committed to the care of patients with noncommunicable diseases, and to direct and evaluate preventive measures.

Adult↗
PubMed2001

Wheat seed proteins exhibit a complex mechanism of protein elasticity.

Elastomeric proteins are found in a number of animal tissues (elastin, abductin and resilin), where they have evolved to fulfil a range of biological functions. All exhibit rubber-like elasticity, undergoing deformation without rupture, storing the energy involved in deformation, and then recovering to their initial state when the stress is removed. The second part of the process is passive, entropy decreasing when the proteins are deformed, with the higher entropy of the relaxed state providing the driving force for recoil. In plants there is only one well-documented elastomeric protein system, the alcohol-soluble seed storage proteins (gluten) of wheat. The elastic properties of these proteins have no known biological role, the proteins acting as a store for the germinating seed. Here we show that the modulus of elasticity of a group of wheat gluten subunits, when cross-linked by gamma-radiation, is similar to that of the cross-linked polypentapeptide of elastin. However, thermoelasticity studies indicate that the mechanism of elastic recoil is different from elastin and other characterized protein elastomers. Elastomeric force, f, has two components, an internal energy component, f(e), and an entropic component, f(s). The ratio f(e)/f can be determined experimentally; if this ratio is less than 0.5 the elastomeric force is predominantly entropic in origin. The ratio was determined as 5.6 for the cross-linked high M(r) subunits of wheat glutenin and near zero for the cross-linked polypentapeptide of elastin. Tensile stress must be entropic or energetic in origin, the results would suggest that elastic recoil in the wheat gluten subunits, in part, may be associated with extensive hydrogen bonding within and between subunits and that entropic and energetic mechanisms contribute to the observed elasticity.

Elasticity↗
PubMed2001

Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization.

We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known.

Alternative Splicing↗
PubMed2001

Alterations of intralesional and lymph node gene expression and cellular composition induced by IL-12 administration during leishmaniasis.

Changes in gene expression and cellular distribution in the lymph node and at the site of infection, the footpad, during Leishmania major infection and/or IL-12 administration were evaluated. Otherwise susceptible BALB/c mice given IL-12 are able to resolve infection. Interestingly, iNOS was not induced in the lymph node by IL-12, yet, nitric oxide is critical in the control of leishmaniasis. However, we observed an increase in iNOS at the lesion site in response to IL-12. These results reflect the importance of examining the primary site of infection. We observed no changes in inflammation at the lesion site; however, IL-12 promoted an early inflammatory response in the lymph nodes. IL-12 administration differentially affected both the local and systemic immune response to invading leishmanial parasites. IL-12 induced iNOS at the lesion site and an early granulomatous inflammation in the lymph node; therefore, we hypothesize that these are key events responsible for the resolution of disease in BALB/c mice treated with IL-12.

Animals↗
PubMed2001

Cerebral asymmetries in the level of attention required for word recognition.

Words presented to the right visual field (RVF) are recognised more readily than those presented to the left visual field (LVF). This RVF advantage could reflect: (a) the direct connection between the RVF and left hemisphere, (b) an attentional bias directed towards the RVF, or (c) an attentional advantage, where the left hemisphere is able to recognise words using less attention than the right hemisphere. The attentional bias and advantage models were tested in 20 dextral adults during a divided visual field word-naming task. Spatial attention was manipulated with valid, invalid, or neutral central cues. Error and reaction time measures revealed a RVF advantage for word recognition. If the attentional bias model is correct, the RVF advantage should have been attenuated for valid and invalid cues compared to neutral cues. Instead of this, an interaction emerged whereby the cueing effect was stronger for words in the LVF than the RVF. This interaction has been reported previously in studies using peripheral spatial cues. The interaction suggests that the RVF requires less attention to process words than the LVF. This left hemisphere attentional advantage may reflect asymmetries between the hemispheres in their word processing styles.

Journal Article↗
PubMed2001

Evaluation of 'Sun-safe': a health education resource for primary schools.

The aim of the study was to assess the effectiveness of 'Sun-safe', a computer-based resource designed to promote skin cancer awareness and educate children, aged 10-11 years, about the effects of excessive exposure to the sun and associated skin cancer preventive behaviours. Effectiveness was measured by changes in knowledge, attitudes and behavioural intentions using a self-completed questionnaire. A cluster, controlled evaluation design was used. Twelve schools were randomly allocated to the intervention arms of the study (workbook or computer), with a further four schools acting as controls (no intervention). One school allocated to the computer group had serious technical problems with their computers on the day of the intervention and had to be excluded from the study, leaving six schools in the workbook group and five in the computer group. One class in each of the 15 schools participated. The questionnaire was administered before the intervention, the day after and 6 weeks thereafter. The primary outcome measures were changes in mean scores at 6 weeks. In all, 376 children, 83% of the roll, completed both pre- and 6-week tests. Mixed-model analysis, allowing for pre-intervention score and the cluster effect, showed significant increases in knowledge scores in all three groups [workbook 2.36, 95% confidence interval (CI): 1.66 to 3.05; computer 1.73, 95% CI: 1.00 to 2.46; control 0.93, 95% CI: 0.11 to 1.74], but only the workbook group was significantly better than the control group (1.43, 95% CI: 0.36 to 2.50) and there was no significant difference between the intervention groups (0.63, 95% CI: -0.38 to 1.63). With regard to attitudes, both interventions showed significantly greater increases in scores than the control group, but there was no significant difference between them (workbook 2.37, 95% CI: 1.27 to 3.47; computer 1.92, 95% CI: 0.76 to 3.09; control -0.01, 95% CI: -1.28 to 1.27). Although the mean increases for behavioural intentions scores were small (workbook 0.66, 95% CI: 0.26 to 1.05; computer 1.11, 95% CI: 0.70 to 1.51; control 0.08, 95% CI: -0.37 to 0.52), those for the intervention groups were significantly better than the control group, but were not significantly different from each other. The evaluation showed significant improvements in knowledge, attitudes and behavioural intentions, which were still present 6 weeks after the intervention. This suggests that interventions employing the Sun-safe workbook and computer-based resources could be most usefully put into effect in the week before the start of the summer holidays.

Awareness↗
PubMed2001

Facing the challenge of practice development in community nursing.

The large number of job titles associated with practice development within nursing can cause confusion as to the exact role of the person working within the development sphere. However, there is a recognized need for these development roles in the absence of clinical managerial positions and within the climate of continuing changes in the NHS. This article explores the skills required for practice development and is, in part, a reflective account of the work achieved over a 2-year period. The authors argue for clarity of purpose and continuing commitment from within the organization in order for these roles to achieve some degree of recognition, with specific reference to a community health care setting.

Community Health Nursing↗
PubMed2000

Selective upregulation of a functional beta7 integrin on differentiating eosinophils.

BACKGROUND: The sequence of adhesion-molecule expression during eosinophil differentiation remains unclear. METHODS: We analyzed the surface expression of alpha4, beta1, and beta7 integrins and compared it to established myeloid developmental markers, using the eosinophilic cell line HL-60 clone 15, as well as cord and peripheral blood differentiation assays. RESULTS: Cells induced to eosinophil differentiation by treatment with butyric acid, IL-5, and GM-CSF showed a significant upregulation of beta7 integrin expression coincident with a marked upregulation of CD35 and attenuation of CD33 and beta1 integrin expression. In addition, adhesion of induced HL-60 clone 15 cells to fibronectin was attenuated by a beta7 integrin antibody. CONCLUSIONS: Our data show that protein synthesis-dependent upregulation of the functional beta7 integrin occurs under conditions when beta4 and beta1 integrins are fully expressed, indicating a sequential appearance of specific adhesion molecules on differentiating eosinophil progenitors.

Antigens, CD↗
PubMed1999

Minimum requirements for remote realtime fetal tele-ultrasound consultation.

We studied the transmission bandwidth required for accurate diagnoses when performing realtime fetal tele-ultrasound consultations. The study was divided into three phases. In phase I, three experienced clinicians evaluated the quality of ultrasound images transmitted at various bandwidths (internally looped back within Brisbane) using eight commercially available codecs at random. The two codecs that performed best proceeded to phase 2, in which a realtime video-link of up to 2 Mbit/s was set up between Brisbane and Townsville (1,500 km apart). Testing with a standard video-tape was performed at seven different bandwidths selected at random, with four clinicians (who were blinded to the equipment and bandwidths used). The optimum line rates for transmission were determined, and testing was then performed using these line rates for fetuses with various anomalies (phase 3). The results showed significant differences in performance according to bandwidths used, but not according to observers. Bandwidths were grouped into three levels. At level I (256 kbit/s) the performance was significantly worse than at level II (384, 512 or 768 kbit/s), which was in turn worse than that at level III (1, 1.5 or 2 Mbit/s). However, within each level, performance at one bandwidth was not significantly different from that at the others. The most cost-effective transmission rates therefore appeared to be 384 kbit/s and 1 Mbit/s. Further testing with fetuses affected by various anomalies confirmed that the majority could be diagnosed using a 384 kbit/s link, with slight improvement in evaluation when the bandwidth was increased to 1 Mbit/s.

Analysis of Variance↗
PubMed1997

Sequencing of the cholesteryl ester transfer protein 5' regulatory region using artificial transposons.

We have isolated and sequenced genomic clones encompassing more than 5 kb of the 5' flanking region of the cholesteryl ester transfer protein gene. This region contains multiple Alu repeats, a Mermaid repeat, and an extensive GA repeat, which made sequencing exceedingly difficult. To circumvent the problems that these repeats posed to traditional sequencing methodologies, we employed a novel transposon-facilitated technique, which greatly simplified sequencing of regions that had been difficult to accomplish otherwise. We utilized the artificial transposon, AT-2, a Bluescript derivative containing the dhfr gene and unique primer sites at both ends of the insertion DNA. Integration of the transposon occurred efficiently and covered the entire region of interest. Analysis of the sequence indicates a number of potential regulatory factor binding sites upstream of the previously characterized minimal promoter. The 5.7-kb regulatory region confers significant transcriptional activation in a conditionally transformed mouse hepatocyte line as compared to a minimal 137-bp promoter fragment. In addition, a tetranucleotide repeat of variable length that may provide a useful genetic marker has been identified 2 kb upstream of the CETP transcriptional start site.

Animals↗
PubMed1997

Migration of elderly people to join existing households: some evidence from the 1991 Household Sample of Anonymised Records.

"In this paper the extent to which migration of the elderly is linked to changing family living situations [in Great Britain] is explored.... [The authors] estimate the number of older people making moves of this type, and...identify their age, sex, and marital status, and their relationship to the household they have joined. It is also possible to say something about the households which these people are joining, in terms of tenure and house type, and to describe the distribution of distances moved."

Adult↗
PubMed1995

In vitro assessment of the effect of methanol and the metabolite, formic acid, on embryonic development of the rat.

Inhalation studies in rats have indicated that methanol is embryotoxic at levels that are only mildly maternally toxic. In the present study, the embryotoxicity of methanol and its metabolite, formic acid, was evaluated using rat embryo culture. The results showed that both methanol and formic acid have a concentration-dependent embryotoxic effect on the developing rat embryo in vitro. The no-effect concentration of methanol was 211.7 mumol/ml culture medium, while embryotoxicity was observed at 286.5 mumol/ml. The no-effect concentration of formic acid was 3.74 mumol/ml, while a concentration of 18.66 mumol/ml was associated with severe embryotoxicity. When embryos were grown in sera containing 18.66 mumol sodium formate/ml or in sera adjusted with hydrochloric acid to pH values similar to those achieved with formic acid, the results indicated that both low pH and formate contributed to the observed embryotoxicity of formic acid. When the level of methanol found to be embryotoxic in the present study is compared to blood levels in the human following controlled industrial exposure there appears to be a large margin of safety. However, plasma methanol levels are only one aspect of methanol toxicity in the human. Of greater significance is the formate level and the associated acidosis. However, it appears that embryotoxicity due to low pH or high formate levels would only occur after very severe methanol intoxication. Based on these in vitro studies, current industrial safety limits would appear to provide protection for the developing embryo.

Animals↗