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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 253 records · Page 14Linked to original sources

Concanavalin A promotes the uptake of lysosomal hydrolases by human fibroblasts.

Human placental hexosaminidase B and beta-galactosidase are taken up very poorly by human fibroblasts in culture. However, if fibroblasts manifesting genetically determined deficiencies of these lysosomal hydrolases are first treated with concanavalin A, then enzyme uptake is markedly increased. Enzyme activity which becomes associated with concanavalin A-treated fibroblasts maintained at 4 degrees C can be greatly removed by treatment with haptene sugar, while enzyme activity which becomes associated with cells maintained at 37 degrees C is refractory to haptens treatment. These results are interpreted as an initial binding of enzyme to concanvalin A molecules located at the cell surface, followed by an active cellular process leading to internalization of the lectin-enzyme complexes.

Biological Transport, Active↗

The association between lead concentrations in teeth and domestic water lead concentrations.

Tooth lead levels have been measured in 109 children living in Glasgow. A significant association has been demonstrated between molar tooth lead concentrations and domestic drinking water lead concentrations. Tooth lead concentrations were found to be greater the longer a child had liver in older housing with lead plumbing during foetal life and following birth. Tooth lead concentrations were also found to be age-related although no difference with respect to social class could be found.

Adolescent↗

Protein binding of salicylate in cutaneous hepatic porphyria.

(1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction.

Blood Proteins↗

Delta-aminolaevulinic acid metabolism in normal and lead-exposed humans.

The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid synthetase (ALA.S) and delta-aminolaevulinic acid dehydratase (ALA.D) were measured in the peripheral blood of a group of lead workers and control subjects. The haem precursor delta-aminolaevulinic acid (ALA) was measured in blood and urine, whilst lead levels were measured in whole blood. The inter-relationships between all these parameters were examined and quantified. The results demonstrate that above a blood lead concentration of 2 mumole/l and below an erythrocyte ALA.D activity of 18 nmole ALA utlized/min/ml red blood cells (R.B.C.), Haem synthesis is depressed to such an extent that the activity of leucocyte ALA.S, the rate-limiting enzyme of haem biosynthesis, is increased by negative feedback.

5-Aminolevulinate Synthetase↗

Effect of certain anaesthetic agents on the activity of rat hepatic delta-aminolaevulinate synthase.

The activity of delta-aminolaevulinic acid synthase (E.C.2.3.1.37) (the rate-limiting enzyme for haem and porphyrin biosynthesis) has been measured in the rat liver after the repeated administration of anaesthetic agents in vivo. The activity of the enzyme was increased by Althesin, chlordiazepoxide, enflurane, etomidate, lignocaine, methohexitone, methoxyflurane, pentazocine and thiopentone and decreased by procaine. No significant changes in activity occurred after the administration of amethocaine, atropine, bupivacaine, diazepam, droperidol, halothane, ketamine, morphine, nitrous oxide, pethidine, phenoperidine, prilocaine and propanidid. It is suggested that those anaesthetic agents which induced activity of the enzyme should not be administered to patients with an acute porphyria.

5-Aminolevulinate Synthetase↗

Approach to the management of pleural effusion in malignancy.

The diagnostic and therapeutic approaches to malignant pleural effusions are reviewed, and data on the retrospective study of 37 patients are presented with respect to diagnosis and management. All patients with stable effusions should be managed with systemic therapy for the primary tumor when an effective agent is available. When it becomes necessary to use local therapeutic measures, thoracostomy tube drainage with local instillation of tetracycline is recommended.

Antineoplastic Agents↗

Erythrocyte delta-aminolaevulinic acid dehydratase activity and changes in delta-aminolaevulinic acid concentration in various forms of anaemia.

Whole blood delta-aminolaevulinic acid (ALA) concentrations and erythrocyte ALA dehydratase activity have been measured in patients with iron deficiency anaemia, megaloblastic anaemia and secondary anaemia, and in normal subjects. ALA concentration was found to be significantly increased in all types of anaemia compared with normal. Erythrocyte ALA dehydratase activity was significantly increased in iron deficiency and megaloblastic anaemia but not in secondary anaemia.

Aminolevulinic Acid↗

Haem biosynthesis in rheumatoid disease.

The activities in blood of six enzymes of the haem biosynthetic pathway have been determined in 12 patients with rheumatoid disease, six of whom were anaemic. The porphyrin and porphyrin-precursor intermediary products of haem biosynthesis were also determined in blood, urine and faeces. No significant differences were found between anaemic and non-anaemic subjects. Failure of delta-amino-laevulinate synthase activity to increase in response to anaemia may be the nature of the marrow unresponsiveness suggested as one factor in the causation of the anaemia. Normal ferrochelatase activity and normal concentrations of free protoporphyrin support the view that iron is effectively unavailable although present in normal amounts. Coproporphyrinogen oxidase activity was significantly depressed.

5-Aminolevulinate Synthetase↗

Hepatic drug metabolism and haem biosynthesis in lead-poisoned rats.

1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, delta-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment.

5-Aminolevulinate Synthetase↗

Evaluation of human chorionic gonadotropin and alpha fetoprotein in benign and malignant testicular disorders.

The marker proteins alpha fetoprotein and human chorionic gonadotropin are useful adjuncts to clinical evaluation of patients with non-seminomatous testicular germ cell malignant growths during and after therapeutic interventions. Measuring both markers is better than measuring either one alone. An elevated marker assay indicates the presence of active disease. A normal marker assay does not exclude active disease being present. Lastly, these markers are of limited usefulness in the evaluation of undiagnosed testicular masses.

Adolescent↗

The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation.

In a group of ten male adults admitted to hospital with clinical symptoms of lead exposure, phenazone, elimination rates, blood delta-amino-laevulinic acid dehydratase (ALA.D) activity, blood lead levels and haemoglobin were measured. Investigations were carried out before, immediately after and again at least 12 weeks after cessation of CaEDTA (sodium calcium edetate) chelation therapy. Following chelation, phenazone elimination rates were increased as assessed by a decrease in half life and increase in clearance. This was significant, both immediately after and 12 weeks after cessation of chelation therapy. The change in rate of phenazone metabolism was associated with improved clinical status, with lowered blood lead levels and raised haemoglobin and ALA.D activity. The results of the study suggest that the depression in phenazone elimination in lead intoxication is possibly due to depressed hepatic cytochrome P450 levels.

Adult↗

Enzyme abnormalities in the porphyrias.

Evidence is presented that each of the porphyrias represents a different inborn error of metabolism in haem biosynthesis. Control of the pathway takes place by feedback repression and inhibition by haem of delta-aminolaevulinic-acid synthase. It is suggested that insituations where the activity of this enzyme is derepressed, prophobilinogen deaminase represents a secondary control step.

5-Aminolevulinate Synthetase↗