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Biomedical subjects

C M Wilson

Publications and source records attributed to C M Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1989

A double blind placebo controlled study of early and late administration of recombinant tissue plasminogen activator in acute myocardial infarction.

Within four hours of the onset of acute myocardial infarction 57 consecutive patients were randomised blindly to infusion of 150 mg recombinant tissue plasminogen activator (rt-PA) (group 1) over five hours or placebo (group 2) when they were first seen outside hospital or in the accident and emergency department. When they were admitted to the coronary care unit patients in group 1 also had placebo infused and those in group 2 were treated with rt-PA as well as placebo. Treatment with rt-PA started at a mean of 119 minutes (range 38-235) after the onset of pain in group 1 and 187 minutes (range 80-285) after the onset of pain in group. In 19 (79%) of 24 in group 1 and 16 of 25 (64%) in group 2 cardiac catheterisation 10-14 days after infarction showed thrombolysis in myocardial infarction grades 2 or 3. There was mean percentage shortening of the infarct related segments (Leighton method) of 16% in group 1 and 10.3% in group 2. For patients with anterior infarction mean percentage shortening was 20.5% in group 1 and 12.2% in group 2. Although there was no significant difference in global ejection fraction as assessed by contrast ventriculography or radionuclide ventriculography the infarct related regional third ejection fraction (a measure of the function of the territory of the affected coronary artery) was significantly improved by early treatment (41% group 1 and 28% group 2). Assessment of infarct size by the QRS scoring method of Palmeri showed QRS score less than or equal to 15/25 patients in group 1 and 8/27 in group 2. Nine patients developed 11 episodes of ventricular fibrillation; all patients in whom ventricular fibrillation developed during treatment with rt-PA were successfully resuscitated. There was no clinically significant bleeding. In seven (12%) patients clinical and electrocardiographic criteria suggested reocclusion. Five patients died from cardiac causes. Prehospital administration of rt-PA was feasible and significantly reduced the delay before thrombolysis was started. Earlier treatment improved myocardial function in the the infarct area and reduced the infarct size.

Adult↗
PubMed1989

Initiation of fetal rat lung phospholipid and surfactant-associated protein A mRNA synthesis.

To determine whether the initiation of fetal lung surfactant phospholipid production and the activation of the gene for the 35-kD surfactant-associated protein are dependent on circulating corticosteroids, we cultured dexamethasone-responsive explants of 15- to 17-d fetal rat lung in medium with 1% FCS (controls), charcoal-stripped 1% FCS, or a variety of glucocorticoid antagonists. The steroid antagonist RU 486 almost completely abolished specific cytoplasmic and nuclear dexamethasone binding in the explants but had no glucocorticoid-agonist activity. There was a significant increase in disaturated phosphatidylcholine synthesis during 7 d in culture in control explants (78%) and in those cultured with Charcoal-stripped serum (83%), RU 486 (82%), or the other glucocorticoid antagonists--clotrimazole, cortexelone, and 11-ketoprogesterone. Specific mRNA for surfactant-associated protein A was not detectable in preculture 17-d lung tissue, but accumulated to the same extent in cultures with or without RU 486 in the medium. These findings support the view that expression of the genes responsible for the synthesis of the various components of surfactant is not induced by glucocorticoids, but by signals contained within the lung tissue itself. The role of circulating hormones is later acceleration and modulation of surfactant production.

Animals↗
PubMed1988

Activities of enzymes of phospholipid and fatty acid synthesis in fetal and adult rat type II pneumocytes.

Although differentiated fetal and adult type II pneumocytes are ultrastructurally similar, it is not known whether there are metabolic differences between them. We measured the activities of selected enzymes of phospholipid and fatty acid synthesis in fetal and adult rat type II cells, in late gestation fetal rat lung explants and in intact lung from rat fetuses of comparable gestational age. The activity of 1-acylglycerophosphocholine acyltransferase was significantly greater in adult type II cells than in fetal type II cells, fetal explants or intact fetal lung. The activity of CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase was similar in fetal and adult type II cells, but significantly lower in explants and intact fetal lung. There was a significant positive correlation between the percentage of alveolar epithelial cells in the cultures and tissue studied and CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase activity. This suggests that the previously reported correlation between phosphatidylglycerol synthesis and the percentage of alveolar epithelial cells in various lung culture systems may be related to the activity of this enzyme. Phosphatidylglycerol synthesis and CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase activity may be metabolic markers of type II cells, whereas the acyltransferase activity may be an indicator of type II cell maturation.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1988

Specificity of androgen resistance in Mus caroli kidney.

Androgen controls the expression of beta-glucuronidase and several other proteins in the kidney of the standard laboratory mouse, Mus musculus. Other species within the genus Mus exhibit a variety of response patterns for kidney beta-glucuronidase and other markers of androgen action. We have investigated the mechanism of androgen action in M. caroli, a Mus species that does not produce beta-glucuronidase in response to testosterone. The failure of testosterone to induce beta-glucuronidase in M. caroli females cannot be overcome by treatment with dihydrotestosterone, with pharmacological doses of testosterone propionate or dihydrotestosterone propionate, or with a variety of potent androgen analogues. All of these compounds induce kidney beta-glucuronidase in M. musculus females and kidney ornithine decarboxylase, submandibular gland renin, and submandibular gland epidermal growth factor in both M. caroli and M. musculus females. Furthermore, kidney androgen receptor proteins from M. caroli and M. musculus animals have the same sedimentation characteristics on sucrose density gradients. These data indicate that androgen resistance in M. caroli is not due to deficient 5 alpha-reductase or aberrant hormone metabolism producing suboptimal levels of functional androgen and is not caused by a defective androgen receptor. They suggest that the resistance of beta-glucuronidase in M. caroli kidney to induction by androgen occurs at the level of the beta-glucuronidase gene.

Androgens↗
PubMed1988

Effect of androgen and thyroid hormones on renin-1 messenger ribonucleic acid levels in mouse submandibular gland.

The synthesis of renin and other biologically active polypeptides in the granular convoluted tubule cells of the mouse submandibular gland (SMG) is regulated by androgen and thyroid hormones. In this study genetically hypothyroid (hyt/hyt) mice carrying a single renin structural gene (Ren-1) were used to investigate the mechanism of hormonal action in mouse SMG. Treatment of female mice with 5 alpha-dihydrotestosterone (DHT) and/or thyroxine (T4) enhanced renin-1 activity and increased renin-1 mRNA, determined by Northern analysis. Compared to euthyroid (hyt/+) littermates, hyt/hyt mice had lower basal levels of renin-1 mRNA and a blunted response to either hormone alone. DHT and T4 acted synergistically to increase renin-1 activity and renin-1 mRNA in the SMG of hyt/hyt females. Furthermore, levels of renin-1 activity and renin-1 mRNA varied concordantly in the SMG of these animals. These data indicate that androgen and thyroid hormones influence levels of renin-1 in mouse SMG primarily by regulating the amount of renin-1 mRNA available for translation.

Animals↗
PubMed1988

Death and damage caused by multiple direct current shocks: studies in an animal model.

Patients who require multiple defibrillator shocks have a poor prognosis. In healthy greyhounds the acute mortality increased as the number of transthoracic shocks (400 J) applied increased (one shock 0/6: five shocks 8/18: 10 shocks 12/17 dogs died acutely from asystole or electromechanical dissociation). The appearance on electron microscopy of the myocardium of these dogs showed few specific abnormal features to account for the total contractile failure that occurs in these dogs. In the survivors, significant ST segment elevation was recorded from the precordial leads of the dogs receiving five and 10 shocks, but not those receiving a single shock. At three days there was significantly more macroscopic cardiac damage in the 10-shock (13.1 +/- 1.8 g) than in the five-shock (7.2 +/- 2.0) group (P less than 0.05). One shock caused little damage. Hence a single high-energy shock was well tolerated in this model. Multiple shocks caused cardiac injury and acute pump failure. These studies indicate the need to reassess why patients die following multiple shocks, and re-emphasise the need for optimized first-shock effectiveness.

Animals↗
PubMed1988

Plasma concentrations of bupivacaine during extradural anaesthesia for caesarean section. The effect of adrenaline.

The clinical effects and plasma levels associated with the use of 0.5% bupivacaine with and without the addition of 1:200,000 adrenaline (5 micrograms/ml) were studied in 30 patients who underwent extradural anaesthesia for elective Caesarean section. The addition of adrenaline to bupivacaine prolongs analgesia, reduces the degree of hypotension and delays its onset. Plasma bupivacaine levels were consistently lower when adrenaline was added, but this difference was significant only at 10 minutes after the initial dose. Prolonging the interval between increments seems to be a more reliable way to reduce plasma concentration than the addition of the catecholamine.

Anesthesia, Epidural↗
PubMed1988

Determination of fecal alpha 1-antitrypsin concentration by radial immunodiffusion: two systems compared.

We compared Helena "QUIPlates" and Calbiochem "LC-Partigen" radial immunodiffusion systems for their ability to measure fecal concentrations of alpha 1-antitrypsin (FA1AT). Reference ranges for FA1AT concentrations in infants receiving various diets, in children, and in adults are given for each system. FA1AT values obtained with Calbiochem LC-Partigen plates averaged 30% greater than those obtained with Helena QUIPlates, but both systems distinguished between normal and high values. Studies involving variations of usual sample-handling procedures showed that storage at room temperature, repeated freezing and thawing, and long-term storage of frozen samples had no significant effect on measured FA1AT concentration. However, values obtained for lyophilized and nonlyophilized samples did not correlate well.

Adolescent↗
PubMed1987

A comparison of the early pharmacokinetics of midazolam in pregnant and nonpregnant women.

The early pharmacokinetics of midazolam were compared in pregnant (active labour, awaiting and during elective Caesarean section) and matched gynaecological patients scheduled to undergo elective hysterectomy, half of whom were given an oxytocin infusion. A standard dose of 5 mg was given intravenously. For the first 15 minutes patients in labour had significantly higher plasma midazolam levels compared to all other groups. This was associated with the largest area under the curve (2 hours), the smallest volume of distribution and lowest clearance. Midazolam when given immediately before Caesarean section, can result in depression of the infant.

Apgar Score↗
PubMed1986

Selective radiolabelling and identification of a strong nucleosome binding site on the globular domain of histone H5.

We describe a chemical investigation of the nucleosome binding site(s) on histone H5. Selective radiolabelling by reductive methylation has led to the identification of lysine residues in H5 that are protected by its association with chromatin. The most strongly protected lysine is Lys-85 which occurs in the globular domain, in a region that is highly conserved between H5 and H1, and in H1 variants, and which probably constitutes a strong binding site for DNA where it enters and leaves the nucleosome. Lysines in the amino-terminal and lysine-rich carboxy-terminal tails are only weakly protected against chemical modification, suggesting a different mode of interaction with DNA.

Amino Acid Sequence↗
PubMed1986

Glucocorticoid stimulation of choline-phosphate cytidylyltransferase activity in fetal rat lung: receptor-response relationships.

A number of previous studies using in vivo and cultured fetal lung models have shown that the activity of choline-phosphate cytidylyltransferase, the enzyme which catalyzes a rate-limiting reaction in de novo phosphatidylcholine synthesis, is increased by glucocorticoids and other hormones which accelerate fetal lung maturation. To examine the mechanism of this glucocorticoid action further, we examined the effect of dexamethasone on cytidylyltransferase activity in cultured fetal rat lung explants and related it to specific dexamethasone binding. Dexamethasone stimulated cytidylyltransferase activity in the homogenate, microsomal and 105,000 X g supernatant fractions. The hormone did not alter the subcellular distribution of the enzyme, however; the bulk of the activity was in the supernatant fraction in both the control and dexamethasone-treated cultures. The dose-response curves for stimulation of cytidylyltransferase activity in the supernatant fraction and specific nuclear binding of dexamethasone were similar and both plateaued at approx. 20 nM. The EC50 for cytidylyltransferase stimulation was 6.6 nM and the Kd for dexamethasone binding was 6.8 nM. The relative potencies of various steroids for stimulating choline-phosphate cytidylyltransferase and for specific nuclear glucocorticoid binding were the same: dexamethasone greater than cortisol = corticosterone = dihydrocorticosterone greater than progesterone. The stimulation by dexamethasone of cytidylyltransferase activity and of choline incorporation into phosphatidylcholine were both abolished by actinomycin D. These data show that the stimulatory effect of dexamethasone on fetal rat lung choline-phosphate cytidylyltransferase activity is largely on the enzyme in the supernatant fraction and does not involve enzyme translocation to the microsomes as has been reported for cytidylyltransferase activation in some other systems. This effect of dexamethasone is a receptor-mediated process dependent on RNA and protein synthesis.

Animals↗
PubMed1986

Effect of pretreatment with ranitidine on the hypnotic action of single doses of midazolam, temazepam and zopiclone. A clinical study.

Patients receiving midazolam, temazepam or zopiclone by mouth as premedication for minor gynaecological surgery were pretreated with either ranitidine or an inert tablet. Pretreatment with ranitidine was associated with a greater degree of drowsiness at 20 and 40 min after midazolam, and a shorter mean time to peak hypnotic effect than in the non-pretreated group. Ranitidine did not affect the degree of drowsiness in the patients receiving temazepam or zopiclone.

Adolescent↗
PubMed1986

Serial analysis of zein by isoelectric focusing and sodium dodecyl sulfate gel electrophoresis.

Zein, the major storage protein of maize (Zea mays L.) endosperm, was extracted from a number of inbreds with alcohol plus a reducing agent. Isoelectric focusing (IEF) separated total zeins into 41 components, while sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separated total zeins into about 15 components. Each procedure gave characteristic patterns of zein bands for a number of maize inbreds. IEF and SDS-PAGE were used serially so that each band separated by IEF could be assayed as an individual SDS-PAGE sample. Some IEF bands revealed only a single band after SDS-PAGE, while others revealed two or more bands. A nomenclature system is presented which integrates the two separation systems with information about chromosome locations of zein genes, maize mutations which affect zein synthesis, and inbred sources for different zeins. SDS-PAGE of zein gives apparent molecular masses which vary widely according to the standards used and the properties of the gels, therefore an artificial nomenclature for identifying zein bands after SDS-PAGE is presented. The new nomenclature provides a flexible system which is useful and can be conveniently used in different laboratories.

Journal Article↗
PubMed1986

Combination treatment with ranitidine and sodium bicarbonate prior to obstetric anaesthesia.

The gastric pH and volume were measured in 175 patients undergoing elective, and 313 undergoing emergency, obstetric procedures. Ranitidine 150 mg was administered orally every 6 hours in labour and at least 2 hours before elective Caesarean section. Patients received 20 ml of 8.4% sodium bicarbonate orally immediately prior to induction of anaesthesia. The combination of ranitidine and sodium bicarbonate produced marked alkalinisation of gastric contents (mean pH 8.9). The administration of sodium bicarbonate pre-operatively in patients who received ranitidine less than 2 hours before operation led to satisfactory elevation of gastric pH. Only four patients had a gastric pH less than 2.5, one patient refused any medication, two received only ranitidine and one patient had a long interval from administration of bicarbonate to aspiration of gastric contents. Gastric volumes were high in labouring patients (mean 84 ml) despite administration of ranitidine. The effectiveness of sodium bicarbonate as a single dose antacid therapy prior to obstetric anaesthesia requires further study.

Anesthesia, General↗
PubMed1986

A double-blind comparison of intramuscular pethidine and nalbuphine in labour.

A double-blind, between-patient comparison of intramuscular pethidine 100 mg and nalbuphine 20 mg for the relief of pain during labour in 80 patients is described. Severity of pain was assessed before and after treatment by subjective pain scores and visual analogue scales. Neither of these methods showed a significant difference between the treatments. Nalbuphine was associated with less maternal nausea and vomiting than pethidine, but this possible advantage was somewhat offset by a tendency of the drug to produce more maternal sedation and dizziness. The mean umbilical vein/maternal vein ratio was significantly higher for nalbuphine (0.78, SEM 0.03) than for pethidine (0.61, SEM 0.02), which suggests easier placental transfer of the former. This finding was reflected in significantly lower 2-4 hour neurobehavioural scores for the infants of mothers given nalbuphine, but there was no significant difference between these scores at 24 hours. On the basis of this study, nalbuphine does not offer a substantial improvement over pethidine for pain relief in labour.

Adult↗
PubMed1985

Mapping of zein polypeptides after isoelectric focusing on agarose gels.

Isoelectric focusing of zein in agarose gels gives sharp separations of at least 25 bands noted among 25 corn-belt inbreds. Six inbreds provided standard bands which were used to construct a pattern map. A method is provided for comparing bands, identified by distance from the cathode, which differ only slightly in position. The 25 inbreds were separated into five groups on the basis of pattern similarity. Some groups contained inbreds derived from widely different sources. Zein isoelectric focusing in agarose should be useful for genotype identification and for determination of varietal purity.

Genetic Variation↗