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Biomedical subjects

M J Lewis

Publications and source records attributed to M J Lewis.

At least 235 records · Page 13Linked to original sources
PubMed1986

Blood lead levels in children in the north-west of Adelaide.

Capillary blood lead levels were investigated in a sample of 513 children of preschool age who were drawn from an industrial working-class region of Adelaide. The geometric mean lead level was 16.3 micrograms/dL. Fourteen children (2.7%) had a blood lead level of at least 30 micrograms/dL, which is designated by the National Health and Medical Research Council as "the level of concern". Boys tended to have higher lead levels than did girls, and children who lived closer to the inner city generally had higher levels than did those who lived further away. Compared with most other Australian findings, the blood lead levels in this study tended to be high. We suspect that the age groups that were studied, and the industrial urban quality of the region that was included, would have had an important bearing on this finding. However, the proportion of children with elevated lead levels in this study did not seem high when compared with US data for children in a comparable age range.

Australia↗
PubMed1986

Influence of endothelium on drug-induced relaxation of the rabbit aorta.

The influence of endothelium on relaxation induced by glyceryl trinitrate (GTN) and isoprenaline (I) has been studied in isolated rabbit aortic ring preparations, in the resting state and after constriction with 5-hydroxytryptamine (5HT). In resting preparations relaxant responses to GTN and I were smaller in the presence of endothelium. In preparations constricted with 5HT relaxant responses to GTN and I were conversely greater in the presence of endothelium. These paradoxical findings are discussed in relation to basal release of endothelium derived relaxant factor.

Animals↗
PubMed1986

Structure and assembly of the endoplasmic reticulum: biosynthesis and intracellular sorting of ERp61, ERp59, and ERp49, three protein components of murine endoplasmic reticulum.

Rabbit antibodies have been prepared against ERp61, ERp59, and ERp49, three protein components of rough endoplasmic reticulum (RER) purified from mineral oil-induced plasmacytoma 315 (MOPC-315) tissue. Analysis of subcellular fractions of MOPC-315 tissue by an immunoprecipitation procedure demonstrated that all three endoplasmic reticulum proteins (ERps) were most enriched in the RER. Immunologically cross-reacting proteins of similar molecular weight have been detected in other eucaryotic cell lines. We have used these antibodies to study the post-translational processing and biosynthetic sorting of the three ERps in pulse-labeled MOPC-315 cells. No larger precursor forms of the ERps were detected and none of the ERps were found to possess asparagine-linked oligosaccharide moieties. We have used a sucrose gradient analysis of pulse-labeled MOPC-315 cells to study the biosynthetic sorting of ERp61, ERp59 and ERp49 and have found no evidence to suggest that these proteins ever leave the endoplasmic reticulum. In addition, all three ERps appeared to have luminally exposed domains. ERp61 and ERp59 were entirely protected by the ER membrane in the absence of detergent, while ERp49 was a transmembrane protein that also possesses a cytoplasmically exposed domain. We have used the anti-ERp antibodies to quantitate the synthesis and accumulation of the three ERps during lipopolysaccharide (LPS)-induced lymphocyte differentiation. After 48 h of culture in the presence of LPS, the synthesis of ERp49 increased sixfold relative to that in control cells. The synthesis and membrane accumulation of ERp61 and ERp59 were less affected by the LPS treatment. Thus, membranes isolated from LPS-treated cells were enriched in ERp49 relative to those isolated from control cells.

Animals↗
PubMed1986

Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium.

The production (synthesis or release or both) of endothelium derived relaxant factor was studied in rabbit aortic strip preparations and an aortic-coronary artery bioassay system. Production of endothelium derived relaxant factor was rapidly inhibited by agents that inhibit mitochondrial electron transport or F1-ATPase, or which uncouple oxidative phosphorylation, but was only slowly impaired by inhibition of glycolysis. It was dependent also on the presence of extracellular calcium with a rapid on-off response time. This study shows that production of endothelium derived relaxant factor appears to be dependent on both oxidative phosphorylation and extracellular calcium.

Acetylcholine↗
PubMed1986

An association between chronic neutrophilic leukaemia and multiple myeloma with a study of cobalamin-binding proteins.

Two patients are described who had evidence of both multiple myeloma and chronic neutrophilic leukaemia at or near the time of presentation. Descriptions of five similar patients were found in the literature supporting an association between the two disorders. This association is further evidence of a link between myeloproliferative and lymphoproliferative disorders. Cobalamin-binding studies of the plasma and neutrophils from one of these patients showed a gross elevation of plasma unsaturated TC I and abnormal neutrophils which contained TC I but not TC III.

Aged↗
PubMed1986

Molecular relationships between trimethoprim R plasmids obtained from human and animal sources.

A total of 65 trimethoprim R plasmids (35 obtained from human strains and 30 from animal strains of Escherichia coli) were examined by the technique of restriction endonuclease fingerprinting. Plasmids belonging to incompatibility groups B, FII and I delta obtained from human and animal sources showed close similarities within each group. Plasmids belonging to incompatibility groups I alpha and P were also obtained from both human and animal sources, but there was no conclusive evidence of close relationships within the groups. Restriction endonuclease fingerprinting was found to be useful for obtaining information about the epidemiology of R plasmids. Its main limitation in this study related to broad host range plasmids of the P incompatibility group, some of which contained very few sites susceptible to cleavage by the restriction endonucleases tested.

Animals↗
PubMed1986

Endothelium-derived relaxing factor alters calcium fluxes in rabbit aorta: a cyclic guanosine monophosphate-mediated effect.

1. Measurement of tension and 45Ca influx and efflux were used to study the effects of endothelium-derived relaxing factor (EDRF), sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) on contractile responses and calcium movements in aortic ring preparations of the rabbit. 2. EDRF activity, induced by stimulating endothelium-containing rings with acetylcholine, was associated with relaxation of noradrenaline-constricted rings and with a marked reduction of noradrenaline-stimulated increase in calcium influx. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations. 3. EDRF also inhibited noradrenaline-stimulated calcium efflux. Sodium nitroprusside and 8-bromo-cyclic GMP had a similar effect in de-endothelialized preparations, both in the presence and absence of extracellular calcium. 4. The vascular smooth muscle relaxant effect of EDRF and of nitrovasodilators may be effected by a cyclic GMP-mediated reduction of cytosolic calcium, through both inhibition of calcium influx and reduction of intracellular calcium release.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Involvement of ATP in the nuclear and nucleolar functions of the 70 kd heat shock protein.

The major heat shock protein, hsp70, is an ATP-binding protein which is synthesized in very large amounts in response to stress. In unstressed, or recovered, mammalian cells it is found in both nucleus and cytoplasm. Under these conditions, its interaction with nuclei is weak, and it is readily released from them upon lysis of cells in isotonic buffer. After heat shock, hsp70 binds tightly first to some nuclear component(s) and then to nucleoli. It can be released from these binding sites rapidly and specifically in vitro by as little as 1 microM ATP, but not by non-hydrolysable ATP analogues. Studies of hsp70 deletion mutations show that the ability of mutants to be released by ATP correlates with their ability to migrate to heat-shocked nucleoli and aid their repair in vivo. We propose a model in which ATP-driven cycles of binding and release of hsp70 help to solubilize aggregates of proteins or RNPs that form after heat shock. Cells also contain proteins related to hsp70 that are synthesized in the absence of stress. The most abundant of these shows the same behaviour as hsp70 after heat shock, and thus may perform a related function in both normal and stressed cells.

Adenosine Triphosphate↗
PubMed1985

Structure and assembly of the endoplasmic reticulum. Biosynthetic sorting of endoplasmic reticulum proteins.

We have studied the post-translational processing and the biosynthetic sorting of three protein components of murine endoplasmic reticulum (ER), ERp60, ERp72, and ERp99. In pulse-labeled MOPC-315 (where MOPC-315 represents mineral oil-induced plasmacytoma cells) plasmacytoma cells, no precursor forms of these proteins were detected and only ERp99 was sensitive to endoglycosidase H. The ERp99 oligosaccharide remained endoglycosidase H sensitive during a 3-h chase, and analysis by high performance liquid chromatography showed the predominant structure to be Man8GlcNAc2. We have used a sucrose gradient analysis of pulse-labeled MOPC-315 plasmacytoma cells in order to directly study the biosynthetic sorting of both glycosylated and nonglycosylated ERps and have found no strong evidence to suggest these proteins ever leave the endoplasmic reticulum. In spite of their common sorting pathway, these proteins differ in their membrane orientation. Both ERp60 and ERp72 are entirely protected by the endoplasmic reticulum membrane while ERp99 appears to have a large domain exposed on the cytoplasmic face of the endoplasmic reticulum.

Animals↗
PubMed1985

Evidence that cyclic guanosine monophosphate (cGMP) mediates endothelium-dependent relaxation.

The mechanism of action of endothelium-derived relaxant factor (EDRF) was studied using aortic strip preparations of the rabbit and a bioassay system of a rabbit coronary artery perfused in series with an intact aorta. Methylene blue (an inhibitor of guanylate cyclase) inhibited, and 2-O-propoxyphenyl-8-azapurine-6-one (MB22948, an inhibitor of cGMP phosphodiesterase) potentiated the vascular effects of EDRF whether these were due to its basal or to stimulated release. Infusion of these agents at different sites in the bioassay indicated that they act pharmacologically at the smooth muscle level and not on release of EDRF or by chemical interaction with EDRF. The data are consistent with the hypothesis that EDRF-induced relaxation is mediated by elevation of smooth muscle cGMP levels.

Animals↗
PubMed1985

Oesophageal stimulation lowers exertional angina threshold.

The effect of oesophageal stimulation with acid on the exertional angina threshold was examined in 12 subjects. Each walked until the angina threshold was reached on four successive occasions; during two tests the oesophagus was instilled with 0.1 mol/l hydrochloric acid and during the other two with physiological saline. Oesophageal instillation was carried out for 20 min at rest before each walk. In 10 patients the angina point was reached after walking a significantly shorter distance on the treadmill when acid was instilled than when the saline was instilled. ST-segment changes and rate-pressure product were not significantly different during the acid and saline tests. The mechanism responsible for the reduction of angina threshold is not known. However, the effect was more pronounced in the 6 patients who had experienced regular oesophageal symptoms than in those who had not. Ischaemic heart disease and gastro-oesophageal reflux are both common, and the possibility that acid reflux may aggravate angina should be borne in mind, particularly when oesophageal symptoms are present.

Adult↗
PubMed1985

Frequency-dependent depression of myocardial contractility by slow calcium channel blocking drugs.

The negative inotropic effects of two dihydropyridine and two non-dihydropyridine calcium slow channel blocking drugs were studied using ferret isolated papillary muscle preparations contracting both isotonically and isometrically. The degree of inotropic depression was found to be dependent on the frequency of stimulation for all four agents. Frequency dependence of inotropic effect was of the order: nifedipine less than felodipine less than diltiazem less than verapamil.

Animals↗
PubMed1985

Structure and assembly of the endoplasmic reticulum. The synthesis of three major endoplasmic reticulum proteins during lipopolysaccharide-induced differentiation of murine lymphocytes.

Monospecific rabbit antibodies have been prepared against ERp72, ERp99, and ERp60, major protein components of a detergent-solubilized extract of endoplasmic reticulum purified from mineral oil-induced plasmacytoma 315 tissue. When subcellular fractions of mineral oil-induced plasmacytoma 315 tissue were assayed by an immunoprecipitation procedure, all three endoplasmic reticulum proteins (ERps) were found to be enriched in the rough endoplasmic reticulum. In murine lymphoid cells, the three ERps represent two major structural classes of protein. Both ERp72 and ERp60 contain no endoglycosidase H-sensitive, N-linked oligosaccharides. On the other hand, ERp99 is glycoprotein containing, in all likelihood, one endoglycosidase H-sensitive oligosaccharide. Immunologically cross-reacting proteins of similar molecular weight have also been detected in other eukaryotic cell lines. The anti-ERp antibodies were used to quantitate the synthesis and accumulation of the three ERps in splenic lymphocytes cultured in the presence and absence of bacterial lipopolysaccharide (Escherichia coli serotype B5:055) (LPS). In the presence of LPS, lymphocytes differentiate from resting cells into actively secreting cells. The synthesis of ERp72 and ERp99 increased 3- and 10-fold, respectively, in response to LPS. The synthesis of ERp60 does not change significantly. The turnover rates for these three proteins are similar in both control and LPS-treated lymphocytes. As a result, membranes isolated from LPS-treated cells are enriched in ERp72 and ERp99.

Animals↗
PubMed1985

Antiarrhythmic and electrophysiological effects of alpha adrenoceptor blockade during myocardial ischaemia and reperfusion in isolated guinea-pig heart.

An isolated buffer perfused guinea-pig heart preparation has been used to study the antiarrhythmic and cellular electrophysiological effects of alpha adrenoceptor blockade during myocardial ischaemia and reperfusion. Phentolamine 5 X 10(-6) M and indoramin 2 X 10(-6) M significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischaemia and reperfusion. Both drugs prolonged action potential duration (APD) and refractory period and reduced Vmax during normal perfusion and these effects were maintained during ischaemia. Reperfusion led to prompt recovery in all hearts but with initial transient shortening of APD. Phentolamine and indoramin abolished shortening of the APD whether added prior to ischaemia or immediately prior to reperfusion, and attenuated the reduction in refractory period, due to higher values at the end of ischaemia. Myocardial catecholamine depletion also significantly reduced ventricular tachycardia and ventricular fibrillation during ischaemia and reperfusion. Catecholamine depletion had similar effects on APD, refractory period and conduction, but phentolamine produced no additional effects when added to catecholamine depleted hearts suggesting that the effects observed here are mediated via adrenergic rather than direct myocardial effects.

Adrenergic alpha-Antagonists↗
PubMed1985

Myocardial reoxygenation damage: can it be circumvented?

We investigated whether reoxygenation damage could be prevented by interventions directed towards reducing calcium influx only during the reoxygenation period. We measured reoxygenation contracture and recovery of contractile performance, using isolated papillary muscle preparations from cat and rabbit, pretreated with ouabain so as to exaggerate the phenomenon of reoxygenation contracture. Reoxygenation contracture was abolished and contractile recovery achieved by lowering extracellular calcium during early reoxygenation and then gradually replacing it. Gradual reoxygenation only postponed contracture and contractile failure. The slow channel blocker, diltiazem, but not verapamil or lidoflazine--in similarly negative inotropic concentrations of 10(-4) mol X litre-1, 10(-4) mol X litre-1 and 2 X 10(-5) mol X litre-1 respectively--reduced early reoxygenation contracture, as did Mg2+ (30 mmol X litre-1), Mn2+ (8 mmol X litre-1), or metabolic acidosis (pH 6.5), without in any case allowing contractile recovery. These observations indicate that reoxygenation damage is not an irrevocable consequence of the preceding hypoxic insult. They imply that calcium entry during early reoxygenation contributes both to contracture and contractile failure, that this occurs through paths other than the slow calcium channel, and that diltiazem may have properties additional to those of blocking the slow calcium channel.

Animals↗
PubMed1985

Plasma cobalamin-binding and serum cobalamin in patients with folate deficiency.

Plasma unsaturated R-binder and transcobalamin 2 (TC 2) levels were measured in 62 patients with folate deficiency and compared with 80 control subjects and 52 patients with pernicious anaemia. An increase in unsaturated R-binder concentration was found in the majority of patients with folate deficiency and with PA. In folate deficiency, however, the unsaturated R-binder was often elevated whether the serum cobalamin (Cbl) was low or normal, more frequently when the serum Cbl was normal. Results of a separate in vivo study of plasma retention of injected 57Co cyanocobalamin were consistent with these findings. An elevated TC2 was found in a small number of patients with folate deficiency and with PA. The serum Cbl appears to the maintained at a normal level in some patients with folate deficiency by an increase in R-binder, which is caused by folate deficiency itself.

Adult↗