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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 163 records · Page 9Linked to original sources
PubMed1986

Food iron and lead absorption in humans.

Food iron and lead absorption were measured simultaneously in 28 subjects by extrinsically labeling three consecutive meals with the radioactive tracers, iron 59-sulfate and lead 203-chloride. Absorption was measured directly in all subjects by whole-body counting and indirectly in 15 subjects by assessing subsequent levels of tracer in blood. Iron status of the subjects ranged from iron deficient to replete, thus providing a wide range of iron absorption. Statistically significant positive correlations were obtained between food-iron and lead absorption measured by whole-body counting and also between the tracer levels of iron and lead in the blood. However, the correlation between the absorption of the two elements was not strong, as evidenced by the fact that only 50% of the subjects who hyperabsorbed iron also hyperabsorbed lead.

Administration, Oral↗
PubMed1986

Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria.

Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. Protoporphyrinogen oxidase in cultures of Epstein-Barr virus transformed lymphoblasts from twenty-seven patients showed a mean maximal velocity (Vmax) of 0.39 +/- 0.08+ nmol of protoporphyrin mg protein-1 h-1, a 52% reduction (P less than 0.001) from a non-porphyric control group (0.82 +/- 0.10). Km values (1.00 +/- 0.27 microM) did not differ significantly (P greater than 0.05) from control values in any of the patients. The mean Vmax of porphobilinogen deaminase in the cultures was 1.50 +/- 0.18 nmol of uroporphyrin mg protein-1 min-1, a 24% reduction (P less than 0.001) from controls (1.94 +/- 0.14). Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8.37 +/- 1.99 nmol of uroporphyrin 1 erythrocytes-1 s-1, a 28% reduction (P less than 0.001) from normal (11.98 +/- 2.11). The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases.

Ammonia-Lyases↗
PubMed1986

The neurotoxicology of lead.

In the past six years, our research group has investigated the relationship between lead exposure and mental and behavioural development. This has been carried out through studies in children and animals. Earlier studies in children have shown that associations might be expected between environmental exposure to lead and various aspects of cognitive and behavioural development. Our study has examined and continues to examine, a cohort of children sub-divided into three groups according to the level of lead exposure during early 'in utero' development. Data amassed to date includes measurement of psychometric function and post natal development, together with biochemical measures of lead exposure. Assessment will continue through to early scholastic performance and will include measurement of deciduous tooth lead concentration as an integrated measure of long term exposure. In addition to these studies in children, a series of neurochemical studies have been carried out using a rat model of lead exposure. Data obtained from both our own neurochemical experiments and those of other groups indicate an extremely complex plethora of neurotoxic actions of lead.

Amino Acids↗
PubMed1986

Quantitative studies on the effects of hormones on structure and porphyrin biosynthesis in the harderian gland of the female golden hamster. II. The time course of changes after ovariectomy.

The Harderian gland of the golden hamster is an important model of porphyrin biosynthesis. In the female, ovariectomy leads to changes in porphyrin production and gland structure. The present study demonstrates that these changes are progressive and independent of age and environmental factors which may have similar effects. Porphyrinogenic enzyme activity decreases with time after ovariectomy while tubule wall degeneration and neutrophilic infiltration increase. Tubule degeneration leads in turn to porphyrin stores (normally intraluminal) occurring increasingly in the interstitial tissue of the gland, either as large accretions surrounded by foreign body giant cells or as small deposits inside individual free macrophages. Between 20-30 weeks after ovariectomy, the frequency of mitotic figures begins to increase accompanied by a transient rise in porphyrinogenic enzyme activity. Mast cell numbers (both in the gland and its capsule) increase markedly with time after ovariectomy.

5-Aminolevulinate Synthetase↗
PubMed1986

Hemodialysis-related porphyria cutanea tarda--treatment failure with charcoal hemoperfusion.

A 56-yr-old man presented with a photosensitive bullous dermatosis 1 yr after commencing hemodialysis. Urinary porphyrin levels were normal and fecal porphyrin levels only minimally increased, but the plasma uroporphyrin concentration was markedly elevated, being higher than that normally occurring in porphyria cutanea tarda. The high plasma uroporphyrin level was thought to result from the combined effects of increased porphyrin production and failure of adequate clearance by hemodialysis. Chronic alcohol ingestion, methyldopa therapy and elevated iron and aluminum levels may have contributed to the porphyrin overproduction. Charcoal hemoperfusion proved unhelpful in lowering the plasma uroporphyrin concentration.

Charcoal↗
PubMed1985

Chester porphyria: biochemical studies of a new form of acute porphyria.

A previously unrecognised form of acute porphyria has been identified in a large family in Chester, UK. Patients presented with attacks of neurovisceral dysfunction and none had experienced cutaneous photosensitivity. Biochemically, the excretion pattern of haem precursors varied between individuals; some had a pattern typical of acute intermittent porphyria, others showed that of variegate porphyria, and some had an intermediate pattern. Studies of the enzymes of haem biosynthesis in peripheral blood cells showed a dual enzyme deficiency, with reduced activity of both porphobilinogen deaminase, as seen in acute intermittent porphyria, and protoporphyrinogen oxidase, as seen in variegate porphyria. The genetic basis of this dual form of acute porphyria and its relation to the other acute porphyrias are not clear.

5-Aminolevulinate Synthetase↗
PubMed1985

The effects of chronic low lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery ligation in anesthetized rats.

The aim of this study was to investigate whether chronic (1, 3, 6, 12, or 16 months) low lead (5 or 25 ppm), administered as lead acetate in the drinking water, commencing either after weaning or from conception, altered the susceptibility of the heart to arrhythmias induced by coronary artery ligation in pentobarbitone anesthetized male Sprague-Dawley rats. The cardiac effects of chronic (3 or 12 months) administration of lead (25 ppm) were also examined in spontaneously hypertensive rats. Treatment from weaning of normotensive rats with 5 or 25 ppm lead for periods of 1, 3, or 6 months had no statistically significant effect on the severity of ischemia-induced arrhythmias. Each of the groups treated from conception with 5 or 25 ppm lead for periods of 1, 12, or 16 months exhibited a higher incidence of ventricular tachycardia than the appropriate control group, but the difference was statistically significant only in the case of animals treated with 25 ppm lead for 12 months. The incidence of ventricular fibrillation was significantly higher in rats treated from conception for 16 months with 5, but not with 25 ppm lead. Spontaneously hypertensive rats treated with 25 ppm lead for 3 but not for 12 months had significantly more ectopic beats than control Sprague-Dawley rats. Lead treatment for the longer exposure periods only caused significant accumulation of lead in the blood whereas all lead treatments resulted in a marked accumulation in the bone. We conclude that chronic exposure to low concentrations of lead does not consistently alter susceptibility of the heart to ischemia-induced arrhythmias in anesthetized rats

Administration, Oral↗
PubMed1985

A progestin effect on lactate dehydrogenase in the human breast cancer cell line T-47D.

The human breast cancer cell line T-47D has high levels of progesterone receptor even in the absence of exogenously added estrogen. Because of this it is a good line in which to study aspects of progestin action. It has been shown by others that lactate dehydrogenase in MCF-7 cells is responsive to estrogen but not to progesterone. Other proteins in other systems have been found to be responsive to both estrogen and progesterone, often requiring priming by estrogen, presumably to produce sufficiently high quantities of progesterone receptor. Reasoning that lactate dehydrogenase in T-47D cells might be stimulated by progestins alone at physiological levels since these cells already have high levels of progesterone receptor, we now report that this is indeed the case.

Breast Neoplasms↗
PubMed1985

Lead in water, infant diet and blood: the Glasgow Duplicate Diet Study.

The Glasgow Duplicate Diet Study was carried out to investigate the effect of lead in drinking water on the blood-lead of infants. A stratified group of 131 mothers and babies were followed from antenatal registration until the children were 3 months of age. The infants' dietary intakes of lead were assessed by composite water sampling and by the "duplicate diet" technique. Blood-leads were measured from venous samples. Statistical analysis in this paper covers sampling variability, the dependence of diet-lead on water-lead, the relationship of blood-lead in the baby's cord to that in the mother, and the contribution of water-lead to the blood-lead (at 13 weeks) of infants that were bottle-fed. The variation associated with sampling for lead in water was taken into account when estimating the relationship between water-lead and blood-lead and when discussing how standards for their respective concentrations should be linked. The conclusion is consistent with an upper guide value of 0.05 mgl-1 for the concentration of lead in drinking water.

Body Weight↗
PubMed1985

Successful abatement of lead exposure from water supplies in the West of Scotland.

A major problem has existed in the West of Scotland for at least the past century associated with lead uptake by water from leaden water distribution systems. Initial studies in Glasgow from 1969 to 1976 and in Ayr in 1980/1981 showed that not only were water supplies soft, acid in consequence highly plumbosolvent, and that water lead levels were, on average, unacceptably high but that blood lead concentrations were also in excess of acceptable limits. A decision was therefore made by Strathclyde Water Department to carry out remedial water treatment to adjust the water pH. The success of this venture was proven by the parallel rapid falls in blood lead and water lead concentrations in the city of Glasgow. This encouraged the Water Department to institute a similar scheme in the town of Ayr. Work on this commenced in 1981, and in a study of the participants in a previous blood lead survey, a highly significant fall in blood lead concentrations was observed. The equation linking these two parameters was found to follow a curvilinear relationship where blood lead varied as the cube root of the water lead with a highly significant coefficient of correlation. This relationship has been shown to hold across a wide range of water lead concentrations down to 1 microgram/liter. This detailed information allows accurate calculation of acceptable limits of lead exposure from specific sources based upon acceptable blood lead concentrations.

Female↗
PubMed1985

Effects of delta-aminolaevulinic acid on contractile activity in the isolated small intestine of the rabbit. Role of adrenergic receptors.

The porphyrin precursor, delta-aminolaevulinic acid (ALA) at concentrations of 0.23-7.6 mM caused dose-dependent inhibition of spontaneous contractions in isolated preparations of rabbit small intestine, suspended in Ringer-Locke solution. Contractions which returned after inhibition from 3.8 and 7.6mM ALA showed increased amplitude and from 7.6 mM ALA a reduction in rate. Pretreatment with prazosin (10(-7) M) significantly reduced the duration of inhibition exerted by 3.8 and 7.6 mM ALA and also the amplitude of contractions returning after this inhibition. Pretreatment with yohimbine (10(-6) M) and propranolol (7 X 10(-6) M) had no significant effects. Blocking of the release of noradrenaline in preparations by incubation with 6-hydroxydopamine (10(-3) M) or guanethidine (1.5 X 10(-5) M) did not prevent the inhibitory effects of ALA. The alpha 1 agonist, cirazoline (10(-5) M), inhibited contractile activity. This effect was blocked by prazosin (10(-7) M). The alpha 2 agonist, guanoxabenz (10(-5) M) had no detectable effect, in the presence of prazosin, to block any residual alpha 1 actions. It is concluded that alpha 1 receptors mediate inhibitory effects in this preparation and that ALA appears to have direct effects upon these receptors.

Aminolevulinic Acid↗
PubMed1985

Neurotoxic action of lead: effect on tetrahydrobiopterin metabolism in the rat.

The effects of lead, a known neurotoxin on the metabolism of a vital tetrahydrobiopterin cofactor for the hydroxylation enzymes tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase, have been investigated. Reduced availability of this pteridine has the potential to reduce the level of the neurotransmitters noradrenaline, adrenaline and 5-hydroxytryptophan in the brain. Using the rat as a model, increases in tetrahydrobiopterin concentration and in the activity of dihydropteridine reductase, an enzyme involved in tetrahydrobiopterin metabolism, were observed after exposure to lead via the drinking water. Possible explanations for this increased level of tetrahydrobiopterin relate to alterations in the balance between synthesis and salvage of this co-factor.

Animals↗
PubMed1985

Porphyrinogenicity of etomidate and ketamine as continuous infusions. Screening in the DDC-primed rat model.

The porphyrinogenicity of etomidate and ketamine administered as continuous i.v. infusions was screened in the DDC-primed rat model of latent variegate porphyria. Ketamine produced no change from control in 5-aminolaevulinate synthase (ALAs) activity and haem intermediate production in either untreated or DDC-primed rats, and would appear to be safe for use in the patient with genetic porphyria. Etomidate, while producing no significant changes in these parameters in untreated rats, caused a statistically significant 47% increase in hepatic ALAs activity with a corroborative 85% increase in coproporphyrin and a 40% increase in protoporphyrin content, in DDC-primed rats. On these grounds, etomidate must be regarded as potentially porphyrinogenic when administered as a continuous infusion for total i.v. anaesthesia.

5-Aminolevulinate Synthetase↗
PubMed1985

Autonomic neuropathy in acute intermittent porphyria.

Autonomic function was assessed in subjects with acute intermittent porphyria and age- and sex-matched controls using five different bedside tests of cardiovascular reflexes. During the acute attack both parasympathetic and sympathetic tests were impaired, but subsequently improved during remission. Early parasympathetic dysfunction was also detected during remission and in latent asymptomatic acute intermittent porphyria.

Acute Disease↗
PubMed1985

Influence of acid rain upon water plumbosolvency.

The West of Scotland has had particular problems in the past associated with soft acidic water supplies and uptake of lead from domestic plumbing systems by such water. As a consequence of this, health problems related to overexposure to lead have been identified. The current debate on acidification of ground waters by acid rain is therefore particularly pertinent to this area. Studies have shown that even a modest decrease in pH will result in very substantial increase in plumbosolvency. This was found to be of particular importance in the city of Glasgow and town of Ayr, where prior to water treatment, pH values were 6.3 and 5.4, respectively, and where, consequentially, large numbers of homes did not comply with lead in water standards. Closed-loop lime-dosing systems were introduced in both Glasgow and Ayr to increase the pH with immediate decrease in the lead content of the water and, subsequently, blood lead concentrations of the subjects living in these areas. Such closed-loop systems will compensate for any acidity in water supplies, whether of natural origin or originating from acid rain precipitation. However, when such treatment has not been applied, any increase in water acidity due to acid rain which is, in many cases, already unacceptable. which is, in many cases, already unacceptable.

Acids↗