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Biomedical subjects

L D Smith

Publications and source records attributed to L D Smith.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Use of a hollow wire to facilitate angioplasty of occluded vessels.

An USCI 0.038 inch (0.97 mm) floppy tipped hollow wire was used to facilitate the passage of angioplasty guide wires across severe stenoses or vessel occlusions before balloon angioplasty. The hollow wire was passed through a standard 7 or 8 French gauge Judkins coronary catheter to establish whether the obstruction could be breached. This reduced the cost of failure because angioplasty guiding systems were not committed to procedures that were unlikely to be successful. The hollow wire provides stability for the passage of the guide wire and can be used to measure distal pressure and inject contrast. To date it has been used in a total of 15 cases of occluded vessels; it failed to cross the lesion in four cases. Successful angioplasty followed in all patients in whom the lesion was crossed.

Adult↗
PubMed1989

Medication refusal and the rehospitalized mentally ill inmate.

Records of all inmates committed to a state forensic hospital in fiscal year 1982 (N = 472) were studied to examine the inmates' hospital utilization between September 1977 and April 1984 and the reasons for their admissions. Medication refusal, hallucinations and delusions, and threatened or potential violent behavior toward others were the most frequently documented reasons for admission. Medication refusal was associated with a greater number of hospitalizations, shorter hospitalizations, diagnoses of paranoid schizophrenia or schizophreniform disorders, longer prison sentences, and convictions for more serious felonies. Inmates admitted for medication refusal were also likely to be referred concurrently for threatened or potential violent behavior toward others. The study demonstrates the particularly violent nature of a large proportion of the hospitalized mentally ill inmates and the important role of medication refusal in their rehospitalization.

Commitment of Persons with Psychiatric Disorders↗
PubMed1988

Mutations in the Tn10 tet repressor that interfere with induction. Location of the tetracycline-binding domain.

Tetracycline induces transcription of the Tn10 tetracycline resistance gene (tetA) by binding to the tet repressor, thereby reducing the repressor's affinity for two operator sites that overlap the tet promoters. We characterized mutations in the tet repressor (tetRs mutations) that interfere with induction of tetA expression. The mutations were isolated on multicopy Tn10 tet plasmids by selecting for resistance to the inducer 5a,6-anhydrotetracycline. Under these conditions, maximal induction of tetA expression inhibits the growth of Escherichia coli K-12. DNA sequence analysis of 25 spontaneous tetRs mutations identified amino acid changes at 13 different positions clustered near the middle of the 207 amino acid residue sequence of tet repressor. This region (residues 64 to 107) is distinct from the bihelical DNA-binding motif of tet repressor (residues 26 to 47). The capacity of tetRs repressors to bind tet operator DNA and to respond to inducer was examined in vivo in tetA-lacZ fusion strains. In three cases, the capacity of tetRs repressors to bind tetracycline was examined in vitro using cell extracts enriched in repressor. Mutations 64Y (His64----Tyr) and 82H (Asn82----His) reduce the repressor's affinity for tetracycline more than 1000-fold and more than 100-fold, respectively, suggesting that His64 and Asn82 may be part of the inducer-binding site or directly involved in maintaining its conformation. Mutation 103I (Thr103----Ile) reduces the repressor's affinity for tetracycline less than tenfold, yet it interferes with induction to a greater extent than either 64Y or 82H, suggesting that 103I may also reduce the repressor's capacity to undergo a conformational change required for induction. The properties of tetRs mutants suggest that the region of amino acid residues 64 to 107 is involved in inducer binding and in signalling between the inducer-binding and operator-binding domains of the repressor.

Bacterial Proteins↗
PubMed1988

Role of the 3'-poly(A) sequence in translational regulation of mRNAs in Xenopus laevis oocytes.

We investigated the effect of 3'-noncoding and poly(A) sequences on the translation and stability of membrane-bound mRNA (maize zein) and free mRNA (Xenopus beta-globin) by injecting SP6 transcripts into stage 6 Xenopus oocytes. With zein mRNA, the presence or absence of a 3'-noncoding or poly(A) sequence had little effect on mRNA stability over 24 h, and the 3'-noncoding sequence played essentially no role in mRNA translation. With short periods of incubation, e.g. 1-2 h, the presence or absence of a poly(A) tail also had little effect on zein mRNA translation; but after longer periods, translation of the poly(A-) mRNA was significantly reduced. A similar pattern of mRNA translation was observed for poly(A+) and poly(A-) Xenopus beta-globin mRNAs. These differences in translational efficiency correlated with the formation of maximally loaded polysomes (seven-eight ribosomes/mRNA) for the poly(A+) zein mRNA and a failure to form large polysomes with the poly(A-) zein mRNA. These results are consistent with a model in which the 3'-poly(A) sequence of mRNAs facilitates reinitiation of ribosomes during protein synthesis.

Animals↗