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Biomedical subjects

W C Smith

Publications and source records attributed to W C Smith.

At least 19 recordsLinked to original sources
PubMed1992

Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.

We have cloned a cDNA encoding a novel polypeptide capable of inducing dorsal development in Xenopus embryos. RNA transcripts from this clone rescue normal development when injected into ventralized embryos and result in excessive head development at high doses. Therefore, we have named the cDNA noggin, noggin cDNA contains a single reading frame encoding a 26 kd protein with a hydrophobic amino-terminal sequence, suggesting that it is secreted. In Northern blot analysis this cDNA hybridizes to two mRNAs that are expressed both maternally and zygotically. Although noggin transcript is not localized in the oocyte and cleavage stage embryo, zygotic transcripts are initially restricted to the presumptive dorsal mesoderm and reach their highest levels at the gastrula stage in the dorsal lip of the blastopore (Spemann organizer). In the neurula, noggin is transcribed in the notochord and prechordal mesoderm. The activity of exogenous noggin RNA in embryonic axis induction and the localized expression of endogenous noggin transcripts suggest that noggin plays a role in normal dorsal development.

Amino Acid Sequence↗
PubMed1992

Adipose tissue fatty acids in Scottish men and women: results from the Scottish Heart Health Study.

The fatty acid composition of adipose tissue from 4114 men and women across 22 districts of Scotland is described. A biopsy of subcutaneous adipose tissue was obtained from the upper arm using a skin biopsy punch. Overall the proportion of saturated fatty acids was lower in women and those of monounsaturated and polyunsaturated higher than in men. There were significant effects of age on adipose tissue fatty acid composition, particularly in women, where the proportion of saturated fatty acids decreased and that of monounsaturated fatty acids increased with advancing age. The fatty acid composition of adipose tissue varied among the districts studied. The district standardised mortality ratio for coronary heart disease was positively correlated with the district mean oleic acid value and inversely correlated with the district mean linoleic acid value. This paper supports the importance of adipose tissue fatty acids as indicators of risk factor status for coronary heart disease.

Adipose Tissue↗
PubMed1992

Social status and coronary heart disease: results from the Scottish Heart Health Study.

Social status has frequently been found to be associated with the prevalence of coronary heart disease. Currently, in developed countries, it seems that the least advantaged social groups are at the greatest risk. This article addresses this issue in the Scottish population, using a cross-sectional sample of 10,359 men and women. Four measures of social status are used: level of education, years of education, housing tenure, and the Office of Population Censuses and Surveys' definition of social class based on occupation. By each of these four criteria, and for both sexes, the least advantaged have a significantly higher coronary heart disease prevalence (P less than 0.01). The odds ratios for housing tenure are highest, being 1.63 and 1.55 for men and women, respectively, comparing those who live in rented accommodation with owner-occupiers. After adjustment for a number of coronary heart disease risk factors, which are possible confounding variables, most, if not all, of the significant effect of education and occupation on coronary heart disease is removed. Housing tenure is still highly significant (P less than 0.001), with odds ratios of 1.48 and 1.45 for men and women, respectively. Smoking and fibrinogen are the most important confounding variables for men, and body mass index, high-density lipoprotein cholesterol, and triglyceride levels, the most important for women. When relationships among the social factors themselves are investigated, housing tenure is found to remove the significant effects of education and occupation in men, and of education in women. No other social factor removes the significant effect of housing tenure (P less than 0.001). Housing tenure in Scotland is thus found to be the most discriminatory measure of social status in relation to coronary heart disease.

Adult↗
PubMed1992

Retinoids in the lateral eye of Limulus: evidence for a retinal photoisomerase.

The lateral eyes of the horseshoe crab Limulus contain about 80 pmoles of retinal, 30 pmoles of retinol, and 4 pmoles of retinyl esters. More all-trans than 11-cis isomer was found in each category of retinoid. No consistent changes were observed in the amounts of retinal, retinol, or retinyl esters as a function of time of day. No 3,4-dehydro- nor hydroxyretinoids were found. Aqueous extracts of the eye support the stereospecific formation of 11-cis retinal from all-trans retinal when irradiated with light. The reaction requires a protein that is apparently recognized by polyclonal antibodies raised against the retinal photoisomerase extracted from honeybee eyes. The isomerase is able to use as substrate either endogenous all-trans retinal in the extract of retinal supplied in vesicles of phospholipid. The spectral efficiency of this isomerization has lambda max at 550 nm, but the spectrum appears too narrow compared with the absorbance spectrum of retinoid-binding proteins, probably because of inadequate correction for nonspecific isomerization at short wavelengths.

Animals↗
PubMed1992

Rheological determinants of blood pressure in a Scottish adult population.

OBJECTIVES: To examine the relationship of blood pressure with haematocrit, plasma viscosity, whole blood viscosity and plasma fibrinogen. DESIGN: A random population sample of 1264 men and women aged 25-64 years from the west of Scotland, UK. RESULTS: Strong correlations between age, body mass index and blood pressure were noted: these were higher for women than men. Blood viscosity, haematocrit and plasma viscosity correlated with blood pressure independently of age, body mass index and smoking status. No evidence was found for an effect of erythrocyte rigidity upon blood pressure; plasma fibrinogen showed an inverse correlation with blood pressure and the rheological variables on multivariate analysis. CONCLUSIONS: Our findings support the role of blood viscosity in determining blood pressure as suggested by other, smaller studies. The magnitude of the effect upon blood pressure levels across the normal range of blood viscosity was of clinical importance. Further studies of factors that influence blood and plasma viscosity may help in the understanding of the aetiology of essential hypertension and its management.

Adult↗
PubMed1992

Diagnostic efficacy of endovaginal color Doppler flow imaging in an ectopic pregnancy screening program.

The authors compared the diagnostic yield of endovaginal color and pulsed Doppler ultrasound (US) in conjunction with endovaginal sonography with that of endovaginal sonography alone in patients prescreened to be at increased risk for ectopic pregnancy. Pelvic structures were evaluated for overall vascularity and for the presence of characteristic pulsed Doppler US velocity waveforms. The diagnostic sensitivity of the initial endovaginal sonographic examination increased with the addition of color and pulsed Doppler US, from 71% to 87% for ectopic pregnancy, from 24% to 59% for failed intrauterine pregnancy, and from 90% to 99% for viable intrauterine pregnancy. Specificities for endovaginal sonography with color and pulsed Doppler US ranged from 99% to 100%. Use of endovaginal color and pulsed Doppler US increased the percentage of diagnostic initial sonographic examinations from 62% to 82%. The improved diagnostic sensitivity of endovaginal color Doppler US for ectopic pregnancy may ultimately result in earlier treatment, with reduced morbidity and mortality.

Color↗
PubMed1992

Time trends and geographical variation in Parkinson's disease in Scotland.

Parkinson's disease is a common and disabling condition which principally affects the elderly. The time and space distribution of Parkinson's disease has been examined to determine if it provides clues as to aetiology and factors affecting its distribution. Previous studies have used mortality data, data from epidemiological studies, and prescribing information particularly with regard to the use of levodopa. These studies have looked within countries and between countries.

Aged↗
PubMed1992

Stimulation by growth hormone (GH) of GH receptor-associated tyrosine kinase activity.

We have shown previously that GH receptors (GHRs) become phosphorylated on tyrosyl residues when GH-responsive cells are exposed to GH. In this work we investigate the molecular mechanism by which GH binding stimulates tyrosyl phosphorylation of GHR. To test whether in the presence of GH, GHR and the tyrosine kinase responsible for GHR phosphorylation are tightly associated in a complex or form a transient enzyme-substrate complex, the rate of in vitro phosphorylation of GHR was determined as a function of receptor concentration. GH-GHR complexes were purified from 3T3-F442A fibroblasts by immunoadsorption to and elution from immobilized phosphotyrosyl-binding antibody. The rate of in vitro tyrosyl phosphorylation of GH-GHR complexes was not substantially reduced when the GHR preparation was diluted 1:10 or 1:100 before phosphorylation, consistent with a tight association between kinase and substrate (GHR). When cells were labeled metabolically with 35S, and GHRs containing phosphorylated tyrosyl residues were isolated by immunoadsorption to and elution from phosphotyrosyl-binding antibody, the ability to immunoprecipitate 35S-labeled GHR with GHR antibodies was only evident when the cells had been incubated with GH. This indicates that in vivo, GHRs are phosphorylated on tyrosyl residues only when GH is bound. Additionally, when anti-GHR antibodies were used to immunoprecipitate GHR from solubilized cells, only GHRs isolated from GH-treated cells were phosphorylated when subjected to an in vitro kinase assay. The increased tyrosyl phosphorylation of GHR detected after incubation of cells with GH is consistent either with GH increasing tyrosine kinase activity associated with the GHR or with GH inducing a conformational change in GHR that renders it susceptible to tyrosyl phosphorylation. To discern whether GH binding increased GHR-associated kinase activity, we tested the ability of anti-GHR antibody immunoprecipitates to phosphorylate the synthetic substrate poly(Glu4,Tyr). GH treatment of cells resulted in a 2-fold increase in the rate of phosphorylation of poly(Glu4,Tyr). The increase in kinase activity was dose dependent, with half-maximal stimulation between 15-20 ng/ml GH. These results provide strong evidence that GH actually increases tyrosine kinase activity associated with the GHR. This would be consistent with GH-dependent complex formation between a constitutively activated kinase and GHR and/or activation of a constitutively associated or intrinsic kinase.

Animals↗
PubMed1992

Variation in coronary risk factors by social status: results from the Scottish Heart Health Study.

The relationship between social status and coronary heart disease in the United Kingdom is well established with the more socially disadvantaged being at higher risk. There is also evidence that the levels of most of the known coronary risk factors vary with social status in a way consistent with their relationship to coronary heart disease. Using data from the Scottish heart health study the aim of this study was to quantify, for men and women, the variation in four of the main coronary heart disease risk factors--smoking, serum total cholesterol level, blood pressure and obesity--according to a number of social factors--occupational social class, housing tenure, level of education and employment status. The analyses used both mean risk factor levels as well as the percentages above suggested cut off levels, in order to provide estimates of the percentage of people at risk. All the risk factors, apart from total cholesterol level in men, showed fairly consistent variation across social groups with the more socially disadvantaged being at higher risk. Similar social variation was found for the percentages above the cut off levels, and these indicate that nearly 60% of the Scottish population aged 40-59 years, have one or more risk factors for coronary heart disease. These results suggest that some targeting of health education and management is appropriate, and this is especially relevant as the reforms to the National Health Service set health targets for health authorities and encourage general practitioners to provide health promotion services.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.

Expression cloning from a pool of gastrula cDNAs identified the Wnt family member Xwnt-8 as having dorsal axis-inducing activity in Xenopus embryos. Microinjected Xwnt-8 mRNA was able to rescue the development of a dorsally complete anterior-posterior axis in embryos ventralized by exposure to UV light. Axis induction was observed in embryos injected in either marginal or vegetal blastomeres at the 32-cell stage. Vegetal blastomeres receiving Xwnt-8 mRNA contributed progeny not to the induced dorsal axis, but to the endoderm, a result consistent with Xwnt-8 causing cells to act as a Nieuwkoop center (the vegetal-inducing component of normal dorsal axis formation), rather than as a Spemann organizer (the induced dorsal marginal zone component that directly forms the dorsal mesoderm). Xwnt-8, which is normally expressed ventrally in midgastrula and neurula embryos, appears to mimic, when injected, maternally encoded dorsal mesoderm-inducing factors that act early in development.

Animals↗
PubMed1991

A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter.

Genomic and cDNA sequences for the mouse cellular retinol binding protein I (mCRBPI) are presented. A specific cis-acting element responsible for retinoic acid (RA) inducibility of the mCRBPI promoter was identified and characterized. Deletion mapping of a CRBPI promoter--chloramphenicol acetyltransferase reporter gene construct localized this element to a 259 bp restriction fragment located approximately 1 kb upstream from the transcription start-site. A sequence closely resembling the previously characterized RA response element (RARE) of the RA receptor beta 2 (RAR-beta 2) promoter, and consisting of a direct repeat of the motif 5'-GGTCA-3' separated by three nucleotides, was found within this restriction fragment. Mutation of these 5'-GGTCA-3' motifs to GGAGC and GGGGC abolished RA-inducible transcription whereas a mutation to a direct repeat of the GTTCA motif found in the RARE of the RAR-beta 2 promoter resulted in enhanced inducibility. Oligonucleotides containing the direct repeat of the GGTCA motif were able to confer RA-dependent transcriptional enhancement to the herpes simplex thymidine kinase promoter, as well as to bind directly all three retinoic acid receptors (RARs) alpha, beta and gamma, as determined by gel retardation/shift assays. The control of CRBPI gene transcription by RA-RAR complexes interacting with the RARE characterized here may correspond to a feedback mechanism important in regulating retinoid metabolism and action.

Amino Acid Sequence↗
PubMed1991

Cigarette smoking and employment status.

The smoking habits and health knowledge of the unemployed and the full-time workers were investigated in a cross-sectional study of over 10,000 men and women throughout Scotland. For both sexes (age range 40-59 years), the proportion of current smokers and ever smokers was found to be considerably higher among the unemployed. Only a small part of the difference could be explained by standardisation for social class. The unemployed smokers had began to smoke at an earlier age, with significantly more smoking whilst still at school. Amongst current smokers, the unemployed males reported smoking fewer cigarettes a day, whereas unemployed women smoked more than their full-time counterparts. The reported levels were confirmed by the biochemical measures of smoking; serum thiocyanate and expired air carbon monoxide levels. In contrast to their differences in smoking habit, the two groups were very similar in their knowledge of the hazards of smoking. Smoking habits among the unemployed reflect a complex interaction of financial and both current and previous social factors. Such relationships present a particular challenge to health promotion campaigns.

Adult↗
PubMed1991

Smoking characteristics and inhalation biochemistry in the Scottish population.

Data from a cross-sectional random population sample of 10,359 middle-aged Scottish men and women are used to investigate the relationships between self-reported tobacco consumption and three biochemical markers of tobacco inhalation: expired air carbon monoxide (CO), serum thiocyanate and serum cotinine. These data represent one of the largest samples of these biochemical markers yet analysed. The results show that, for each sex, the biochemical markers are highly correlated for smokers and for the entire sample of mixed smokers and non-smokers. CO is the preferred biochemical marker, in such groups, because it is the cheapest, is non-invasive and gives virtually instantaneous results. Self-reported daily cigarette consumption also correlates well with each of these biochemical markers, and so it appears that people are, in the context of population studies, mainly truthful about their smoking. The relationships with self-reported cigarette consumption are curvilinear with apparent levelling out of the gradient at around 25 cigarettes/day for cotinine and thiocyanate and at greater than 40 cigarettes/day for CO. Sex differences are small, although thiocyanate is generally higher and cotinine generally lower in women with the same self-reported cigarette consumption as men. Amongst non-smokers, only cotinine is able to discriminate between self-reported levels of exposure to passive smoking. CO and thiocyanate are not suitable for measuring low levels of smoke inhalation, such as found in passive smokers.

Adult↗
PubMed1991

Localization of retinal photoisomerase in the compound eye of the honeybee.

The distribution of honeybee retinal photoisomerase, a soluble light-requiring enzyme that stereospecifically forms 11-cis retinal, was investigated by immunoelectron microscopy and by HPLC. Immunolocalization with polyclonal antibodies shows that the highest concentration of retinal photoisomerase is located in the proximal portion of the primary pigment cells in large aggregates (approximately 2 microns diameter). Photoisomerase is also located in the peripheral portion of the photoreceptor cells, laterally displaced from the rhabdom, but in much lower concentration. Because of the larger volume of the photoreceptor cells, about half of the total immunoreactivity is associated with the primary pigment cells. Dissection of the eye with the subsequent use of HPLC to assay for photoisomerase activity showed that most of the photoisomerase activity is associated with tissues near the cornea. The same tissue also supports the reduction of 11-cis retinal to 11-cis retinol. These biochemical findings are consistent with the immunolocalization of retinal photoisomerase to the high-concentration aggregates in the primary pigment cells that surround the crystalline cones. The major synthesis of 11-cis retinol therefore takes place in the primary pigment cells, and the retinoid must be moved into the photoreceptor cells to be available to newly synthesized opsin. The immunoreactivity of the photoreceptor cells appears to reflect the presence of some isomerase without an attached retinoid chromophore.

Animals↗
PubMed1991

Nutrient intakes of different social-class groups: results from the Scottish Heart Health Study (SHHS).

Food frequency questionnaire and socio-demographic data were collected from over 10,000 Scottish men and women aged 40-59 years in a cross-sectional study of coronary heart disease (CHD) risk factors. Dietary intake, including the antioxidant vitamins C and E and beta-carotene, was assessed for different socio-economic groups. Trends in nutrient intakes were found with social-class (occupational) groups I-V. The non-manual-manual distinctions were clear even after standardizing for serum cotinine, and alternative classification by housing tenure and level of education did not confound the social-class effect. Total energy intake was significantly higher in the manual (men 10,363 KJ, women 7507 KJ) than in the non-manual (men 9156 KJ, women 7169 KJ) groups, and all nutrient amounts except for vitamin C, vitamin E, beta-carotene and fibre were significantly higher in the manual than the non-manual groups. Alcohol intake was lower in manual women, but higher in manual men compared with their respective non-manual groups. Sex and social-class differences were maintained after adjusting for total energy. Women in general, and manual women in particular, had the highest percentage energy from total fat (40.2) and saturated fat (18.2), while the percentage energy from polyunsaturated fat was lower in men than women, and lowest in manual men (4.4). The polyunsaturated:saturated fat (P:S) ratios were, for non-manual and manual men 0.32 and 0.31, and for non-manual and manual women 0.31 and 0.28. Fibre and antioxidant vitamin intakes, when expressed as nutrient densities, were lower in men than women, and lowest in manual men. Overall, men and women in manual occupations had a poorer-quality diet than did those in non-manual occupations. The coincident low P:S ratios and low antioxidant vitamin intakes in manual groups may contribute to an increased risk of CHD. Thus, the findings are compatible with the view that poor diet may be a contributory factor to the higher mortality rates for CHD which occur in the lower socio-economic groups.

Adult↗