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Biomedical subjects

D L Smith

Publications and source records attributed to D L Smith.

At least 343 records · Page 19Linked to original sources
PubMed1988

Epinephrine and left ventricular function in humans: effects of beta-1 vs nonselective beta-blockade.

Changes in cardiac performance in response to epinephrine administered by graded infusion were assessed by M-mode echocardiography in normotensive healthy subjects after pretreatment with placebo, the beta 1-selective blocker atenolol, or the nonselective beta-blocker propranolol. Epinephrine alone increased heart rate and left ventricular end diastolic dimension and decreased left ventricular end systolic dimension. Left ventricular performance as assessed by fractional shortening and systolic blood pressure/end-systolic volume (P/V) ratio was also increased. Atenolol pretreatment did not significantly affect the increase in heart rate by epinephrine. However, atenolol did prevent the effects of epinephrine on left ventricular dimensions and left ventricular performance at the lower infusion rates and significantly blunted these effects at the highest infusion rate. After propranolol, epinephrine significantly decreased left ventricular end diastolic dimension despite decreasing heart rate and left ventricular emptying (associated with a high afterload). P/V ratio remained unchanged. These results indicate that beta 2-receptors may play a major role in the increase in heart rate caused by epinephrine. In contrast, epinephrine's positive inotropic effect appears to be mediated primarily via beta 1-receptors and, at higher concentrations, possibly also through beta 2-receptors. The pattern of changes in left ventricular end diastolic dimension suggests that epinephrine increases venous return via both beta 1- and beta 2-receptor stimulation and that alpha-receptor stimulation (epinephrine after propranolol) may actually decrease venous return.

Adrenergic beta-Antagonists↗
PubMed1988

Calcium absorption from calcium carbonate and a new form of calcium (CCM) in healthy male and female adolescents.

Calcium absorption from two Ca salts was investigated in a crossover design using stable isotopic tracers in 12 healthy adolescents (6 males, 6 females). A Ca supplement in the form of Ca carbonate or Ca citric and malic acids (CCM) was ingested with a standardized breakfast and the order of administration was randomized. The oral supplement contained 250 mg elemental Ca, 21.8 mg of which was highly enriched 44Ca tracer. Thirty minutes later subjects received 3.6 mg 42Ca tracer intravenously. The molar concentrations of 42Ca and 44Ca tracers in a urine sample obtained 24 h after tracer administration were quantified by fast-atom-bombardment mass spectrometry and used to determine fractional absorption of the Ca from the supplement. Ca in the form of CCM had an increased fractional absorption (p less than 0.03) relative to Ca carbonate in healthy adolescents (36.2 vs 26.4%). This increase was not related to body size, sex, or indices of Ca metabolism.

Administration, Oral↗
PubMed1988

Flexibility of the yeast alpha 2 repressor enables it to occupy the ends of its operator, leaving the center free.

The yeast alpha 2 protein, the product of the MAT alpha 2 gene, is a regulator of yeast cell type; it turns off transcription of the a-specific genes by binding to an operator located upstream of each gene. In this paper we describe the domain structure, subunit organization, and some unusual features of the way this protein contacts its operator. We show that the protein is folded into two domains. The carboxy-terminal domain binds specifically to the operator; the amino-terminal domain contains dimerization contacts. The alpha 2 dimer differs from those of the phage repressors in that it is flexible and therefore is able to bind tightly to differently spaced operator half-sites. In the natural operator, the centers of the operator half-sites are two and one-half turns of DNA apart, exposing them on opposite sides of the DNA helix. We show that the design of alpha 2 allows a dimer to reach across its operator such that it occupies the two half-sites but leaves the middle of the operator available to other proteins.

Base Sequence↗
PubMed1988

Topical minoxidil: cardiac effects in bald man.

Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy.

Administration, Topical↗
PubMed1988

The ego (and its superego) reconsidered.

The term 'ego' can be found in Freud's writings from his earliest psychoanalytic works onwards. Hartmann was the first scholar to suggest a solution to some of the apparent ambiguity in Freud's use of the term by distinguishing the self-representation from the structural ego of the second topography. Ultimately, Hartmann sought to confine the term 'ego' to the designation of a theoretical entity as opposed to an experiential reality. A careful reading of Freud reveals that he used the term 'das Ich' to designate both a set of experiences and the theoretical entity formulated to explain them. On the phenomenological level Freud describes the ego in terms of (a) the self representation, (b) the felt sense of existence and (c) the phenomenon of action. An application of this approach to understanding Freud to his accounts of the superego and ego ideal suggests that there is no inherent antagonism between the two concepts and that the difference between the two is fundamentally one of levels of abstraction. The superego emerges as a phase-specific organization of the ego.

Ego↗
PubMed1987

Annonacin, a novel, biologically active polyketide from Annona densicoma.

A new linear polyketide, Annonacin (I), has been isolated from active extracts of the stembark of Annona densicoma Mart. Annonacin (I) is highly cytotoxic and is active in an assay designed to detect antimitotic agents. The structure of (I) was determined by analysis of spectroscopic data.

Antineoplastic Agents↗
PubMed1987

Isolation and structure elucidation of an epoxide derivative of the hypermodified nucleoside queuosine from Escherichia coli transfer RNA.

A new nucleoside has been identified in tRNATyr from Escherichia coli MRE 600, where it replaces the highly modified nucleoside queuosine. The nucleoside is also present in a large amount relative to queuosine in mixed tRNA from E. coli strains MRE 600 and W (from which it was isolated for characterization). The new nucleoside has been characterized as an epoxy derivative of queuosine: 7-(5-[(2,3-epoxy-4,5-dihydroxycyclopent-1-yl)amino]methyl)-7-de azaguanosine, oQ, based on data from directly combined liquid chromatography/mass spectrometry, high resolution mass spectrometry, and proton NMR spectroscopy. Nucleoside oQ is also present in small amounts in mixed tRNA from E. coli B. Isomerization of oQ occurs readily under alkaline conditions to give a rearranged product, oQ', characterized as 7-(5-[(3,4-epoxy-2,5-dihydroxycyclopent-1-yl)amino]methyl)-7-deaza guanosine. The present finding constitutes the first report of epoxide formation during post-transcriptional processing of RNA.

Chromatography, High Pressure Liquid↗
PubMed1987

Assignment of disulfide bonds in proteins by fast atom bombardment mass spectrometry.

A rapid and sensitive method for assignment of disulfide bonds using fast atom bombardment mass spectrometry is described for hen egg white lysozyme and bovine ribonuclease A. The protein is initially digested to a mixture of peptides using chemical and enzymatic methods under conditions which minimize disulfide bond reduction and exchange. The digested sample is analyzed directly by fast atom bombardment mass spectrometry before and after chemical reduction of cystine residues. An important feature of the method is that it is not necessary to completely resolve the peptides in the digest chromatographically prior to analysis. The disulfide-containing peptides are also characterized directly by prolonged exposure of the sample to the high energy xenon atom beam which results in the reduction of cystine residues. Intra- as well as interchain disulfide bond assignments are made on the basis of the mass difference between the molecular ions (MH+) of the oxidized and reduced peptides. Confirmation of the mass assignments may be obtained from the mass spectra of the digests after one cycle of manual Edman degradation. Although the quantity of protein required to unambiguously assign all of the disulfide linkages will depend on the ease with which the appropriate peptide fragments can be formed, results from these studies indicate that approximately 1 nmol of protein is usually sufficient.

Amino Acid Sequence↗
PubMed1987

Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans.

Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.

Adult↗
PubMed1987

Selective turnover of the essential fatty acid ester components of estradiol-17 beta lipoidal derivatives formed by human mammary cancer cells in culture.

The properties of fatty acyl coenzyme A: estradiol-17 beta acyl transferase in microsomes derived from pooled human mammary cancer tissue have been examined. A pH optimum of 5.5 was found and addition of long-chained fatty acyl CoAs increased estradiol-17 beta (E2) 17-monoacyl ester synthesis; the apparent Km for E2 being 8 microM when oleoyl CoA, linolenoyl CoA or palmitoyl CoA were employed. Testosterone, dehydroepiandrosterone, and 5-androsterone-3 beta, 17 beta-diol acted as competitive inhibitors with Ki values of 36, 36 and 46 microM, respectively. The composition of E2 fatty acyl esters (E2-L) formed by incubation of [3H]E2 with human mammary cancer tissue and human mammary cancer cell lines has been determined by HPLC. Although the composition of E2-L in estrogen receptor negative cell lines (MDA-MB-231 and MDA-MB-330) was generally similar to that found for MCF-7 cells (estrogen receptor positive) and pooled human mammary cancer tissue, the former cell lines contained a 3-fold higher relative concentration of E2-17 beta stearate. MCF-7 cells were exposed to 30 nM [3H]E2 and the composition of the isolated [3H]E2-L fraction studied at various time intervals. At 0.5 h, the intracellular concentration of E2-L was 1.8 +/- 0.4 (SEM) pmol/mg DNA which increased to values of 3.6 +/- 0.6 and 4.3 +/- 0.5 at 4 h and 16 h, respectively. In the subsequent 3 h following transfer to medium lacking [3H]E2, the concentration of E2-L declined to 3.7 +/- 0.3 pmol/mg DNA. The subfraction of E2-L composed of E2-17 beta arachidonate, linolenate and docosahexaenoate, was seen to decline in relative abundance after 0.5 h and to reach significantly lower relative levels at 16 h, and again in the 3 h period following estrogen withdrawal. The data suggests that these components, derived from essential fatty acids, are more metabolically active. This may then provide a new lead to link these novel estrogen derivatives with the established relationship between unsaturated fatty acids and an increased mammary cancer incidence.

Acyl Coenzyme A↗
PubMed1987

Platelet aggregation inhibitory activity and vasodepressor activity of a series of bicyclo[3.2.0]hept-6-ylidene iminoxy alkanoic acids with modified lower side chains.

Prostacyclin analogues derived from modification of the lower side chain of the bicyclo[3.2.0]hept-6-ylidene iminoxyacetic acid (1) were studied in inhibition of in vitro and ex vivo platelet aggregation and in the spontaneously hypertensive rat. Iminoxyacetic acids (13a), (13b), (13c) and iminoxypropionic acid (14b) were 2.9, 3.0, 1.9 and 2.0 times respectively more potent than PGE1 in inhibiting ADP-induced aggregation of human platelets in vitro. Following intravenous administration at a dose of 90-110 micrograms/kg in the guinea pig, iminoxyacetic acids (13a), (13c) and iminoxypropionic acid (14b) showed a maximum inhibition of 82-92% with a half life in the range of 14-22 min. Following oral administration at a dose of 1 mg/kg in the guinea pig, iminoxyacetic acids (13a) and (13b) inhibited heterologous platelet aggregation for 4.5 h. Following intravenous administration in spontaneously hypertensive rats, acids (13a)-(13c) and (14b) lowered the mean blood pressure in a dose dependent manner. At a dose of 100 micrograms/kg, the effect lasted for 20-40 min.

Administration, Oral↗
PubMed1987

Hemodynamic interaction of nonselective vs. beta-1-selective beta-blockade with hydralazine in normal humans.

To assess the effects of nonselective vs. beta 1-selective beta-blockade on the hyperdynamic circulation induced by hydralazine, eight healthy volunteers received placebo, propranolol, 20 and 40 mg, and atenolol, 25 and 50 mg, on 5 separate days, followed by hydralazine (range 75 to 150 mg). Hydralazine decreased afterload (end-systolic wall stress) and increased venous return and left ventricular performance (by M-mode echocardiography). Both beta-blockers blunted the increases in heart rate, cardiac output, and venous return similarly, although heart rate and cardiac output were not completely normalized. Atenolol did not affect the hydralazine-induced decrease in afterload, whereas propranolol significantly opposed this change (P less than 0.03). The hyperdynamic circulation seen with hydralazine is mostly beta mediated, primarily beta 1. When given with hydralazine the two beta-blocker types differ primarily in their effects on afterload.

Adolescent↗