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Biomedical subjects

W C Smith

Publications and source records attributed to W C Smith.

At least 163 records · Page 9Linked to original sources
PubMed1989

Recombinant mouse placental lactogen-I binds to lactogen receptors in mouse liver and ovary: partial characterization of the ovarian receptor.

The binding of recombinant mouse placental lactogen-I (mPL-Ir) to liver and ovarian membranes was investigated in virgin and pregnant mice. Competitive binding assays demonstrated that mPL-Ir, mouse placental lactogen-II (mPL-II), and mouse PRL (mPRL) bind to the same receptors in ovarian membranes. The relative abilities of the three hormones to displace [125I]iodo-mPL-Ir from the ovarian lactogen receptors was mPL-II greater than mPL-Ir much greater than mPRL. Scatchard analysis of mPL-Ir binding to ovarian membranes from day 10 pregnant mice showed a Ka of 2.0 x 10(9) M-1 and a binding capacity of 3.2 x 10(-14) mol/mg membrane protein. The specific binding of [125I]iodo-mPL-Ir to ovarian membrane preparations was significantly higher on day 17 than on day 10 of gestation. Dissociation of endogenous hormones with 4 M MgCl2 increased the binding of [125I]iodo-mPL-Ir to ovarian membranes but not to liver membranes. Affinity cross-linking of [125I]iodo-mPL-Ir to liver and ovarian membranes resulted in the specific labeling of proteins with receptor mol wt (Mr) of 44K and 40K (nonreduced) and 50K and 42K (reduced), as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lactogen receptors from liver and ovary appeared structurally homologous, producing fragments with similar Mr when treated with proteolytic enzymes and undergoing similar reductions in Mr when treated with glycolytic enzymes. The ability of mPLs to bind specifically and with high affinity to receptors in mouse ovarian membranes suggests that these hormones may regulate ovarian function during gestation.

Animals↗
PubMed1989

Hamster placental lactogen-II contains a structural feature unique among the growth hormone-prolactin-placental lactogen family.

Sequence analysis of cDNA for hamster placental lactogen-II (PL-II) revealed that while this protein has a high degree of sequence homology to mouse and rat PL-II it contains a pair of cysteine residues not present in the mouse and rat proteins or in any other known member of the GH-PRL-PL protein family. This unique pair of cysteine residues may be responsible for the extreme tendency of hamster PL-II, compared to other members of the GH-PRL-PL family, to form disulfide-bonded hormone-serum protein complexes.

Amino Acid Sequence↗
PubMed1989

Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains.

Predicted amino acid sequences for the mouse GH receptor and the related serum GH binding protein were deducted from cDNAs. Two types of cDNA clones were isolated. Both types coded an identical peptide domain with extensive homology to the extracellular domains of the recently cloned human and rabbit GH receptors. However, while one type of clone also encoded regions with homology to the transmembrane and cytoplasmic domains of the human and rabbit GH receptors, the other encoded a short hydrophilic carboxyl-terminal region in place of the transmembrane domain. It is speculated that these two types of clones encode the high and low molecular weight variants of the mouse GH receptor/serum binding proteins, respectively. The low molecular weight variant has been previously found to constitute the majority of the serum GH binding activity in mice. It is proposed that the substitution of the hydrophilic tail for the transmembrane domain may give the low molecular weight variant its soluble nature and account for its presence in serum.

Amino Acid Sequence↗
PubMed1989

The peripheral hypoechoic rim of the fetal heart.

The purpose of this study is to determine the origin of the hypoechoic rim around the fetal heart; this rim has been noted previously but there is disagreement as to its origin. Of 314 fetuses scanned, a four-chamber view was obtained in 290; a hypoechoic rim was present in 94% of these. In all cases in which a short-axis view could be obtained, the rim continued circumferentially through the ventricular septum. Because the rim continues through the septum, it cannot be pericardial fluid but is instead part of the myocardium. The presence as well as the origin of this normal hypoechoic rim around the fetal cardiac ventricles should be considered before diagnosing small pericardial effusions.

Diagnosis, Differential↗
PubMed1989

Amiodarone.

Amiodarone is an antiarrhythmic agent with unique electrophysiological and pharmacokinetic properties and a wide spectrum of antiarrhythmic activity. Its clinical efficacy is not confined to ventricular arrhythmias but extends to supraventricular arrhythmias including those associated with Wolff-Parkinson-White Syndrome. Though a highly effective drug, amiodarone causes significant side effects. In this article, the electrophysiologic and pharmacokinetic properties, the clinical efficacy, and the adverse effects of amiodarone are reviewed.

Amiodarone↗
PubMed1989

Practical automation and interpretation of quantitative assays of antibodies to therapeutic proteins, illustrated with human growth hormone.

To quantify concentrations of anti-growth hormone antibody in less than 600 serum samples by radioimmunoassay, we devised a system ("BOLAC") to process data and to execute the curve-fitting program LIGAND-PC automatically with an IBM PC-compatible computer. We fit data from each sample to four binding and one or two-antibody binding sites. Total antibody concentration is then calculated from the model that is statistically "best". This process occasionally selects a two-binding-site model that severely overestimates the antibody concentration. Errors of this kind are discarded by constraining the product of the second-site antibody's affinity and its concentration to exceed a minimum value (0.05). We evaluated the performance of the BOLAC system by assaying controls and by using computer simulations to demonstrate the high confidence levels attainable in estimation of antibody concentrations. Between-assay variability (CV) was less than 25%, and analytical recovery exceeded 90%. These figures are acceptable for an assay based on curve-fitting of competitive radioimmunoassay data, allowing clinically relevant assessments of antibody responses in patient's samples. The advantages of the BOLAC system include high throughput and the reporting of results in absolute units of affinities and concentrations.

Animals↗
PubMed1989

Ayrshire and Arran coronary prevention programme--baseline risk factor survey.

Scotland has very high mortality rates for coronary heart disease in both men and women. The Ayrshire and Arran health Board Area is co-terminus with four local government districts which all have male coronary mortality rates above the Scottish average. A survey of lifestyle and coronary risk factors was conducted in these four districts in preparation for the launch of a Prevention Programme's 'Healthy Heart Campaign'. This survey will be used as a baseline for evaluation of lifestyle modification and risk factor change over the next 5-10 years. The information provided by the survey is valuable to the direction and targeting of the Prevention Programme. The methods developed in this survey could be used for evaluation of other coronary prevention programmes. Similar data has been collected from another 20 districts as part of the Scottish Heart Health Study and has been distributed to all the Scottish mainland health boards.

Adult↗
PubMed1988

Urinary electrolyte excretion, alcohol consumption, and blood pressure in the Scottish heart health study.

As part of a study of risk factors for coronary heart disease 24 hour urine collections were obtained from 7354 men and women aged 40-59 selected at random from 22 districts throughout Scotland (Scottish heart health study). The mean of two standardised measurements of blood pressure was related to the reported consumption of alcohol and measurements of height, weight, pulse rate, and electrolyte excretion. Several significant correlations were found with both systolic and diastolic pressure, but only the coefficients for age, body mass index, and pulse rate were greater than 0.1. Alcohol consumption showed a weak positive correlation with blood pressure in men. Sodium excretion showed a weak positive correlation with blood pressure in both sexes, and potassium excretion showed weak negative correlations. In multiple regression analysis age, pulse rate, body mass index, alcohol consumption, and potassium excretion had significant independent effects but sodium excretion did not. Although measuring blood pressure twice on one occasion and 24 hour urinary sodium excretion only once may have weakened any potential correlation, the most likely explantation of these results is that the relation between sodium and blood pressure in the population is weak and that potassium and alcohol are of greater importance.

Adult↗
PubMed1988

Evaluation of a portable measure of expired-air carbon monoxide.

There are a variety of independent methods of estimating smoking status; measurement of expired air carbon monoxide has proven to be reliable and convenient. This article describes a new, inexpensive, portable analyzer for measuring expired-air carbon monoxide --the Bedfont EC50. We have compared this analyzer with the standard instrument for measuring expired-air carbon monoxide in 138 normal subjects and found good correlation and agreement. The Bedfont was demonstrated to be better at identifying smoking status, and the relevance of this finding for classification of smokers and nonsmokers by fixed-threshold carbon monoxide levels is discussed. The features of the Bedfont EC50 are particularly appealing for field and clinical use.

Adult↗
PubMed1988

Successful nonsurgical treatment of cervical pregnancy with methotrexate.

Although cervical pregnancy is a rare complication of gestation, previously described treatments are associated with a high morbidity. A case of cervical pregnancy successfully treated without surgery is presented. When the diagnosis is made early in gestation, the use of methotrexate should be considered for the treatment of cervical pregnancy when future fertility is desirable.

Abortion, Induced↗
PubMed1988

Detection of two growth hormone receptor mRNAs and primary translation products in the mouse.

Two mouse growth hormone-receptor primary translation products of Mr 95,900 and 31,800 were identified from in vitro-translated late pregnant mouse liver mRNA. RNA isolated from mouse liver was translated in a rabbit reticulocyte lysate system containing [35S]methionine, and the growth hormone receptor primary translation products were identified by immunoprecipitation with anti-mouse growth hormone receptor antiserum followed by sodium dodecyl sulfate/PAGE and fluorography. Detectable amounts of the Mr 95,900 and 31,800 proteins were not present in in vitro-translated nonpregnant mouse liver mRNA. This result is consistent with previous observations of the up-regulation of growth hormone receptors in the liver during pregnancy in the mouse. Northern (RNA) blot analysis of mouse liver and adipose tissue RNA with a rabbit growth hormone receptor cDNA probe revealed two hybridizing mRNAs of approximately 3.9 and 1.2 kilobases. These two RNAs were greatly up-regulated in liver, but not in adipose tissue, during pregnancy. The sizes of these mRNAs closely matched predictions of the sizes of the mRNAs coding for the proteins of Mr 95,900 and 31,800 made by in vitro translation of size-fractionated late-pregnant mouse liver poly(A)+RNA. These results suggest a mechanism for the generation of both the heterogeneous forms of the growth hormone receptor identified in mouse liver membrane preparations and the mouse serum growth hormone-binding protein.

Animals↗
PubMed1988

Cardiovascular risk factor profile and mortality in two Scottish cities.

Edinburgh and Glasgow are the two largest cities in Scotland, which has one of the highest coronary heart disease mortality rates in the world. Within Scotland, there is a geographical variation in these rates and Glasgow has a higher mortality rate than Edinburgh. However, the cities also differ socially and economically. Population surveys have been conducted in centres in both Edinburgh and North Glasgow using the MONICA project methods. These surveys were performed simultaneously in 1986 in men and women aged 25-64 years. Preliminary analysis shows that the differences in cigarette smoking, blood pressure and body mass index in men and women between the two centres are consistent with the difference in cardiovascular mortality. However there is no difference between the centres in reported exercise levels, and the difference in mean serum total cholesterol between the centres is in the opposite direction to that expected. Possible explanations of these differences are discussed.

Adult↗
PubMed1988

Hepatic placental lactogen receptors during pregnancy in the mouse.

The binding sites for mouse placental lactogen-II (mPL-II) in virgin and pregnant mouse hepatic membranes were analyzed by Scatchard analysis and affinity cross-linking. Competitive binding studies showed that mPL-II and mouse PRL (mPRL) bound to the same receptors in all liver membrane preparations, although the affinity of mPRL binding was lower than that of mPL-II binding. Two classes of receptors for mPL-II, high and low affinity, were found by Scatchard analysis. The concentration of both types of sites in liver membranes increased during pregnancy. In contrast, the affinity of both sites for mPL-II was highest in virgin female mice and declined during pregnancy. Cross-linking of [125I]iodo-mPL-II to maternal liver membranes resulted in the specific labeling of one major protein species of 67,000 daltons as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Under nonreducing conditions, two bands of approximately 63,000 and 60,000 daltons were apparent. Subtraction of the mol wt of mPL-II (22,000, reduced; 20,000, nonreduced) from the mol wt of the cross-linked complex indicated that the mol wt of the receptor was 45,000 under reducing conditions and 43,000 and 40,000 under nonreducing conditions. These observations suggest that mPL-II receptors may be present in mouse liver membranes in at least two forms.

Animals↗
PubMed1988

Gestational profile and affinity cross-linking of the mouse serum growth hormone-binding protein.

The modulation of the serum concentration of mouse GH-binding protein during gestation was characterized. A rapid increase in the concentration of the binding protein began on day 9 of pregnancy and peaked by day 15. The increase in the serum GH-binding protein concentration was preceded several days by an increase in the hepatic GH receptor concentration. The serum GH-binding protein was recognized by antibodies produced against the hepatic GH receptor, and its mol wt (major form mol wt, approximately 41,800) was similar to that of low mol wt forms of the hepatic GH receptor, demonstrating the similarity of the serum GH-binding protein and the hepatic GH receptor. The apparent affinity of the serum GH-binding protein for mGH in untreated serum samples from 17-day pregnant mice was 6.9 X 10(7) M-1. However, when the serum was treated to remove endogenous GH, the apparent affinity increased to 1.5 X 10(8) M-1. Likewise, the binding capacity of the GH-binding protein in serum differed in treated (60.1 nM) and untreated serum (101.2 nM).

Animals↗
PubMed1988

Isolation of two molecular weight variants of the mouse growth hormone receptor.

GH receptors (GHRs) have been shown by affinity cross-linking to be present in late pregnant mouse liver microsomes in three forms with cross-linked mol wts of 125,000, 62,000, and 56,000. The two lower mol wt forms of the receptor were partially purified by bovine GH-affinity chromatography of 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate-solubilized extracts of late pregnant mouse hepatic microsomes. The GHRs were identified from the partially purified receptor preparation and isolated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isolated GHRs had mol wts of 40,700 and 37,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Enzymatic cleavage of N-linked glycosylation from the isolated GHRs reduced their apparent mol wts to 33,600 and 30,900, respectively. Sixteen of the amino-terminal 17 amino acid residues of the two isolated receptors were sequenced and determined to be identical. One amino acid residue in each of the proteins, at position 14, could not be identified. Rabbit polyclonal antiserum was produced against the isolated GHRs. The resulting antiserum precipitated the isolated 40,700 and 37,500 mol wt proteins as well as cross-linked mouse GHRs (including the high mol wt form of the receptor). However, the antiserum did not inhibit the binding of mouse GH to either membrane bound or 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate-solubilized GHRs.

Animals↗