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Biomedical subjects

W C Smith

Publications and source records attributed to W C Smith.

At least 109 records · Page 6Linked to original sources

Expression of TRPM-2 during involution and regeneration of the rat liver.

Increased message levels of testosterone-repressed prostate message-2 (TRPM-2) have been associated with programmed cell death in many tissues. To study its involvement in the apoptotic elimination of hepatocytes during liver involution and regeneration, levels of TRPM-2 message were evaluated in situ and by the ribonuclease protection assay. Although significant increases in apoptotic bodies were observed in rats 96 h following treatment with lead nitrate and ethylene dibromide, an increase in TRPM-2 message was not detected. Therefore, the expression of TRPM-2 mRNA may be a poor indicator of the extent to which apoptosis occurs during liver involution.

Animals↗

Opsins from the lateral eyes and ocelli of the horseshoe crab, Limulus polyphemus.

cDNA clones encoding opsins from the lateral eyes and median ocelli of the horseshoe crab, Limulus polyphemus, were isolated from cDNA libraries. The opsin cDNAs obtained from the lateral eye and ocellar libraries code for deduced proteins with 376 amino acids. The two cDNAs are 96% identical at the nucleic acid level, differing primarily at the 3' untranslated region, and are apparently the products of two separate genes. The deduced opsin proteins are 99% identical to each other, differing at only 5 amino acids. The opsins encoded by these cDNAs are most likely the protein moiety of the visible-wavelength rhodopsins in this animal. In the lateral eye, expression of the opsin gene is restricted to the photoreceptor cells of the ommatidia. Comparisons with opsins of other species show that the Limulus opsin proteins are most similar (53% identity) to the opsin from the R1-6 photoreceptors of flies.

Amino Acid Sequence↗

Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm.

A dorsalizing signal acts during gastrulation to change the specification of lateral mesodermal tissues from ventral (blood, mesenchyme) to more dorsal fates (muscle, heart, pronephros). This signal, from Spemann's organizer, cannot be mimicked by the mesoderm inducers activin and fibroblast growth factor. The gene noggin is expressed in the organizer, and could be the dorsalizing signal. Here we show that soluble noggin protein added to ventral marginal zones during gastrulation induces muscle, but that activin does not. Dorsal pattern can be partially rescued in ventralized embryos by injection of a plasmid that expresses noggin during gastrulation. The results suggest that the noggin product may be the dorsalizing signal from the organizer.

Activins↗

Plasma fibrinogen in women: relationships with oral contraception, the menopause and hormone replacement therapy.

Plasma fibrinogen was measured in 4837 women aged 25-64 years as part of the Scottish Heart Health Study and Scottish MONICA population surveys. The relationships of oral contraceptive use, the menopause and hormone replacement therapy were examined. Univariate analyses found that women with a history of oral contraceptive use, premenopausal women and those on hormone replacement therapy all had significantly lower fibrinogen levels than women who had never used oral contraceptives, postmenopausal women and non-hormone replacement users respectively. These differences persisted after age standardization. On multivariate analysis, menopausal status and hormone replacement therapy had independent effects on fibrinogen levels. Together with the common risk factors, 9.9% of the total variation in plasma fibrinogen levels was explained. However, less than 1% of this was from the combined menopausal and hormonal factors. These results confirm a postmenopausal rise in fibrinogen level which may be relevant to an increased risk of coronary heart disease. In addition, a protective effect with hormone replacement therapy is noted, although this was probably due to selection bias.

Adult↗

Point counting on the Macintosh. A semiautomated image analysis technique.

In image analysis, point counting is used to estimate three-dimensional quantitative parameters from sets of measurements made on two-dimensional images. Point counting is normally conducted either by hand only or manually through a planimeter. We developed a semiautomated, Macintosh-based method of point counting. This technique could be useful for any point counting application in which the image can be digitized. We utilized this technique to demonstrate increased vacuolation in white matter tracts of rat brains, but it could be used on many other types of tissue. Volume fractions of vacuoles within the corpus callosum of rat brains were determined by analyzing images of histologic sections. A stereologic grid was constructed using the Claris MacDraw II software. The grid was modified for optimum line density and size in Adobe Photoshop, electronically superimposed onto the images and sampled using version 1.37 of NIH Image public domain software. This technique was further automated by the creation of a macro (small program) to create the grid, overlay the grid on a predetermined image, threshold the objects of interest and count thresholded objects at intersections of the grid lines. This method is expected to significantly reduce the amount of time required to conduct point counting and to improve the consistency of counts.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗