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L D Smith

Publications and source records attributed to L D Smith.

At least 19 recordsLinked to original sources
PubMed1992

Evidence that Mos protein may not act directly on cyclin.

Using affinity-purified antiserum we have examined cyclin B2 levels in Xenopus oocytes at various stages of oogenesis. We found that cyclin B2 is detected from stage 2 to stage 6 as two bands, one of which is phosphorylated, and that cyclin B2 mass increases about 28-fold between stage 2 and stage 6. To examine the effect of Mos protein on cyclin phosphorylation, we microinjected synthetic Xenopus c-mos (c-mosxe) RNA into stages 4, 5, and 6 Xenopus oocytes. In stage 6 oocytes, maturation was induced by c-mosxe RNA, and, as is the case with progesterone treatment, all cyclin B2 was shifted to the phosphorylated form. However, c-mosxe RNA injected into stage 4 or 5 oocytes did not induce maturation or cause a shift in the relative proportion of the two cyclin B2 bands. These data suggest that Mos does not act directly to phosphorylate cyclin B2, causing the band shift during maturation. Cyclin B2 synthesis increases about 2-fold during maturation, in concert with total protein synthesis. Data from experiments on cyclin B2 stability indicate that the half-life of cyclin B2 is about 85 hr in stage 6. This suggests that if Mos protein has a direct effect on cyclin stability, it does so only at a later stage in oocyte maturation, but not at the onset.

Animals↗
PubMed1992

Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)

To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations.

Angina Pectoris↗
PubMed1992

The phototoxic effect of erythrosin B on third-stage larvae of gastrointestinal nematodes in sheep.

The phototoxic effect of erythrosin B on the infective third-stage larvae (L3) of naturally acquired mixed populations of ovine gastrointestinal nematodes was investigated. This xanthene dye was phototoxic when administered orally to parasitized lambs or applied directly to feces containing nematode ova. Phototoxicity was assessed by the lack of motility (non-swimming) exhibited by the L3 following their collection by Baermannization from cultured feces and exposure to fluorescent light for 360 min. When lambs were administered erythrosin B orally at dosages of O (control), 40, 60 and 80 mg dye kg-1 body weight daily for 10 consecutive days, the percentages of non-swimming L3 were 16%, 46%, 55% and 62%, respectively. However, erythrosin B phototoxicity did not persist after administration of the dye was discontinued and the percentage of non-swimming L3 declined to a level similar to that of the untreated controls within 2 days. The highest percentage of non-swimming L3 was observed when erythrosin B was added directly to feces containing nematode ova. A dose-response curve was evident from the successively higher percentages of non-swimming L3 with increasing concentrations of erythrosin B. Xanthene dyes have the potential to control parasites acquired by livestock on pasture by inducing a phototoxic reaction in the infective L3.

Administration, Oral↗
PubMed1992

Therapeutic bioequivalency study of brand name versus generic carbamazepine.

We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

Adolescent↗
PubMed1991

Isoelectrofocusing of rat muscle adenylosuccinase.

Adenylosuccinase catalyses the conversion of adenylosuccinic acid to AMP and fumarate. We have developed a coupled enzyme staining procedure applicable to nitrocellulose blots after agarose gel isoelectrofocusing of rat muscle adenylosuccinase. The coupling enzymes, fumarase (fumarate to L-malate) and malic enzyme (L-malate to pyruvate and NADPH), are adsorbed to nitrocellulose prior to blotting. The NADPH, mediated by phenazine methosulfate, converts a tetrazolium salt to its blue formazan. This procedure demonstrated that rat muscle adenylosuccinase consists of three isomeric forms present in similar amounts.

Adenosine Monophosphate↗
PubMed1990

Microinjected GTP-gamma-S inhibits progesterone-induced maturation of Xenopus oocytes.

GTP-gamma-S inhibits progesterone-induced maturation of Xenopus laevis oocytes and induces a rise in their cAMP levels. GTP-gamma-S does not inhibit MPF-induced maturation. Although GTP-gamma-S prevents the progesterone-induced increases in protein synthesis and phosphorylation, it has no effect on the basal rates of either. GTP-gamma-S also prevents the initial DAG drop induced by progesterone. GDP-beta-S effects are ambiguous, but it seems not to affect progesterone-induced maturation. These results suggest that although G-proteins are associated with the pathways affected by progesterone, the effects of progesterone are not mediated by a typical receptor/G-protein/effector interaction.

Animals↗
PubMed1990

Retinyl acetate inhibition of 3'-methyl-4-dimethyl-aminoazobenzene induced hepatic neoplasia.

1. Retinyl acetate protected female rats from the hepatocarcinogenic effect of 0.06% 3'-Me-DAB up to 18 weeks. 2. The net effect of retinyl acetate was to retard, not prevent, the action of the hepatocarcinogen since the protection broke down prior to the 30 week time point. 3. The observed elevation of serum LSA by retinyl acetate was unexpected and suggested that some of the difficulties found in its use as a tumor marker may be due to dietary factors. 4. The time necessary for development of preneoplastic lesions in the rats fed 0.01% 3'-Me-DAB was 71 vs 8 weeks for those fed 0.06% 3'-Me-DAB. 5. The effect of retinyl acetate on the lower level of 3'-Me-DAB was to prevent formation of nodules through 71 weeks by which time the unprotected rats fed 0.01% 3'-Me-DAB alone had extensive hepatic nodular development.

Adenylosuccinate Lyase↗
PubMed1990

Comparison of standard (non-oxygenated) vs. oxygenated St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol).

Recent studies have suggested that oxygenation of crystalloid cardioplegic solutions improves myocardial preservation. To assess whether oxygenation of St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol) improves its clinical efficacy, 50 patients were randomly assigned into 2 groups: (1) those receiving Plegisol and (2) those receiving O2-Plegisol (PO2 greater than 500 mmHg at 4 degrees C). Efficacy was assessed by (a) clinical and haemodynamic parameters, (b) quantitative birefringence changes in response to ATP and calcium as a measurement of myocardial preservation in left and right ventricular biopsies, (c) creatine kinase (MB isoenzyme) release for up to 4 days postoperatively, (d) electrocardiographic (ECG) monitoring for up to 7 days postoperatively. There were no differences in mean age, ejection fraction, aortic cross-clamp duration, or bypass duration between the 2 groups of patients. In the Plegisol group, 2 patients (8%) died and 4 patients (16%) required inotropic support, whereas in the O2-Plegisol group there were no deaths and only 2 patients (8%) required inotropic support. These differences, however, were not statistically significant. Birefringence assessment demonstrated an improved myocardial response to ATP and calcium (predominantly in the left ventricular epimyocardium and in the right ventricular biopsies) at the end of ischaemia and after reperfusion in patients given O2-Plegisol. Deterioration in cellular assessment of myocardial contractility (measured by a reduction in birefringence of greater than 0.4 nm) was reduced from 20% in Plegisol patients to 12.5% in O2-Plegisol patients. CK-MB values showed no difference at any sampling time between the 2 groups of patients; a mean peak CK-MB of 35 IU/l occurred 2 h postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

H-ras(val12) induces cytoplasmic but not nuclear events of the cell cycle in small Xenopus oocytes.

Microinjection of H-ras(val12) protein into fully grown Xenopus oocytes has been shown to induce meiotic maturation. In the present study, mRNA encoding the mutant ras protein was injected into both fully grown (stage 6) and growing (stage 4) oocytes. The mRNA induced nuclear breakdown in stage 6 oocytes, as expected. However, the mRNA induced neither nuclear breakdown nor maturation promoting factor when injected into stage 4 oocytes. Instead, the response in stage 4 oocytes included an activation pulse of calcium, cortical granule breakdown, elevation of the vitelline envelope, and abortive cleavage furrows, all of which are characteristics of the activation response in mature eggs. In addition, the injected mRNA led to increased rates of endogenous protein synthesis and the migration of subcortical organelles into the oocyte interior. These observations are discussed relative to the suggestion that oncogenic ras protein leads to an increase in both diacylglycerol and inositol trisphosphate, which then regulate the various cytoplasmic events described.

Animals↗
PubMed1990

Cardiology.

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Angioplasty, Balloon, Coronary↗
PubMed1990

In vivo regulation of MPF in Xenopus oocytes.

Entry into M phase in the eukaryotic cell cycle is controlled by the oscillating activity of MPF. The active component of MPF is now known to be the p34cdc2 protein kinase originally found in yeast. The p34cdc2 protein kinase displays a characteristic M-phase-specific histone H1 kinase activity when it interacts with cyclins, which are proteins that oscillate through the cell cycle and are thought to regulate p34cdc2 activity. Cyclins can induce M phase when introduced into fully grown Xenopus oocytes and cyclin may play a role in normal oocyte maturation. Small Xenopus oocytes do not mature in response to the hormonal triggers which act on stage 6 oocytes. We introduced cyclin into stage 4 (small) Xenopus oocytes and showed that it activates MPF in these cells, probably by interacting with endogenous p34cdc2 kinase. We made labelled extracts from cyclin-mRNA-injected stage 4 oocytes and used them to show differential stability of clam cyclins A and B at oocyte maturation. The relative stability of the two forms of cyclin related directly to their ability to stabilize crude MPF preparations from injected stage 6 oocytes.

Animals↗
PubMed1990

Protein kinase C and progesterone-induced maturation in Xenopus oocytes.

Though progesterone-induced maturation has been studied extensively in Xenopus oocytes, the mechanism whereby the prophase block arrest is released is not well understood. The current hypothesis suggests that a reduction in cAMP and subsequent inactivation of cAMP-dependent protein kinase is responsible for reentry into the cell cycle. However, several lines of evidence indicate that maturation can be induced without a concomitant reduction in cAMP. We show that the mass of diacylglycerol in whole oocytes and plasma membranes decreases 29% and 10% respectively, within the first 15 sec after the addition of progesterone. Diacylglycerol in plasma membranes further decreased 59% by 5 min. We also show that the protein kinase C inhibitors sphingosine and staurosporine can induce oocyte maturation. In addition, the synthetic diglyceride, DiC8, and microinjected PKC can inhibit or delay progesterone-induced maturation. These results together suggest that a transient decrease in protein kinase C activity may regulate entry into the cell cycle. The mechanism whereby DAG is decreased in response to progesterone is unclear. Initial studies show that progesterone leads to a decrease in IP3 suggesting that progesterone may act by reducing the hydrolysis of PIP2. On the other hand, progesterone caused a decrease in the amount of [3H]arachidonate labelling in DAG during the same time suggesting that progesterone may stimulate lipase activity. The relationship between postulated changes in the PKC pathway and those hypothesized for the PKA pathway are discussed.

Alkaloids↗
PubMed1989

Purification and characterization of glucose dehydrogenase from the thermoacidophilic archaebacterium Thermoplasma acidophilum.

Glucose dehydrogenase was purified to homogeneity from the thermoacidophilic archaebacterium Thermoplasma acidophilum. The enzyme is a tetramer of polypeptide chain Mr 38,000 +/- 3000, it is catalytically active with both NAD+ and NADP+ cofactors, and it is thermostable and remarkably resistant to a variety of organic solvents. The amino acid composition was determined and compared with those of the glucose dehydrogenases from the archaebacterium Sulfolobus solfataricus and the eubacteria Bacillus subtilis and Bacillus megaterium. The N-terminal amino acid sequence of the Thermoplasma acidophilum enzyme was determined to be: (S/T)-E-Q-K-A-I-V-T-D-A-P-K-G-G-V-K-Y-T-T-I-D-M-P-E.

Amino Acid Sequence↗
PubMed1989

Clinical validation of St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol).

Recently, the St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol) has become available commercially in the UK. In a series of patients (n = 28) undergoing open heart surgery for a variety of lesions, a clinical validation was performed. Preservation of myocardial contractility was assessed biophysically by quantitative birefringence measurements of myocardial biopsy samples (full thickness apical left ventricle and right ventricle) taken (1) prior to ischaemia, (2) at the end of ischaemia and (3) 10-15 min after reperfusion during cardiopulmonary bypass. In addition, serum CK-MB values were measured in samples taken throughout the operation and for 4 days postoperatively. Postoperative ECG traces (taken every 6 h for 48 h and then daily up to 7 days) were analysed to identify the occurrence of perioperative infarction. There were no hospital deaths. Chronotropic support was required in 5 of 28 patients (18%) for transient heart block. Low cardiac output did not occur postoperatively. Birefringence measurements in biopsy samples taken at the end of the ischaemic period (immediately prior to reperfusion) indicated an apparent left ventricular deterioration in myocardial contractility in 12 of 28 patients (43%) when compared to biopsies sampled prior to the ischaemic period. However, after 10-15 min of aerobic reperfusion, measurements indicated that myocardial contractility recovered to almost pre-ischaemic levels in the majority of patients. Thus, in 22 of 28 patients (79%), left ventricular deterioration did not occur in post-ischaemic biopsy samples when compared to the pre-ischaemic biopsies. Similarly, 21 of 28 patients (75%) had no deterioration of birefringence values in right ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Bicarbonates↗
PubMed1989

Maternal recognition of pregnancy in the goat: effects of conceptus removal on interestrus intervals and characterization of conceptus protein production during early pregnancy.

Goat conceptuses were surgically removed from the uterus at different days during early pregnancy and cultured for 24-30 h in the presence of L-[3H]leucine to determine the effects of embryo removal on the interestrus interval and to characterize in vitro synthesis and release of conceptus proteins. Normal cyclic and animals (controls) exhibited interestrus intervals of 20.44 +/- 0.89 days. Removal of conceptuses on Days 13 and 15 did not alter interestrus intervals compared to cyclic animals. Removal of conceptuses on Day 17 and times thereafter resulted in significant (p less than 0.05) prolongation of interestrus intervals. These results demonstrate that maternal recognition of pregnancy in the goat occurs between Days 15 and 17. Proteins synthesized and released into the medium by conceptuses were first detectable at Day 16 by the analytical method employed (two-dimensional polyacrylamide gel electrophoresis followed by fluorography). The major protein synthesized at this time was acidic (pI = 5.2-5.7) and consisted of two isotypes with molecular weights of about 17,000. Although patterns of protein production became more complex with conceptus development, this protein remained as a major product through Day 21 but not afterwards. This protein, as well as two other low molecular weight acidic proteins (Mr approximately equal to 21,000, 23,000; pI = 5.7-6.0) were shown by immunoprecipitation to react with anti-ovine trophoblast protein-1 (oTP-1) serum. Hence, these products may comprise a caprine trophoblast protein-1 (cTP-1) complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗