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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 289 records · Page 16Linked to original sources
PubMed1977

Effects of aluminium, lead and zinc on delta-aminolaevulinic acid dehydratase.

The effects of aluminium, lead and zinc on ALA dehydratase were examined in vitro and in vivo. Aluminium alone added to the erythrocyte enzyme assay caused a highly significant increase in enzyme activity. A similar result was found with zinc alone. When lead and aluminium were added together, the inhibition found with lead alone was depressed in an additive manner by aluminium. Zinc and aluminium together showed an activation that was stoichiometrically additive. Studies in vivo using rats injected with aluminium and lead showed similar results for hepatic ALA dehydratase as those found in vitro.

Aluminum↗
PubMed1977

Androgenic control of the harderian gland in the male golden hamster.

In the golden hamster, there are marked sex differences in the Harderian gland. Male glands (which are heavier than female glands) possess two cell forms (Type I and Type II cells); female glands only exhibit the former. Female (but not male) glands contain large amounts of porphyrin, which are readily visible as solid depositions within the lumina. The weight, histology and porphyrin content of the Harderian gland was examined in intact adult male hamsters and in male hamsters castrated for 1,2 or 8 months. Castration resulted in a significant reduction in the weight of the gland, the disappearance of Type II cells, and the presence in the gland of solid porphyrin accretions. The levels of copro- and (especially) protoporphyrin were greatly increased. These changes were more marked with time after castration. When the ability of diverse androgens (testosterone, 5alpha-dihydrotestosterone, androst-4-ene-3,17-dione (androstenedione), dehydroepiandrosterone and androsterone) to prevent these changes was tested, testosterone and androstenedione maintained glandular weight. All the androgens maintained normal frequencies of Type II cells and all except dehydroepiandrosterone prevented deposition of porphyrin. The potencies of the various androgens in maintaining normal Harderian gland morphology and activity are compared with their effects on other somatic variables and sexual behaviour.

Androstenedione↗
PubMed1977

Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood.

Hereditary coproporphyria is biochemically distinct from the other porphyrias and is characterized by excessive excretion of coproporphyrin in faeces and usually in urine. The laboratory findings in 28 patients with this disease are presented and the clinical details of eight patients who have been in attack summarised. The remaining 20 patients were latent for the disease. In all patients studied the activity of delta-aminolaevulinic acid synthase was raised and coproporphyrinogen oxidase depressed in the leucocyte. This indicates the partial enzyme block in the haem biosynthetic pathway in this disease. The activities of the other enzymes in the pathway, leucocyte ferrochelatase and erythrocyte delta-aminolaevulinic acid dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase showed no consistent change. On review of 111 cases, 35 per cent presented in acute attack: 80 per cent had abdominal pain, 34 per cent vomiting, 29 per cent solar sensitivity, 23 per cent neurological involvement, 23 per cent psychiatric symptoms and 20 per cent severe constipation. Only two fatalities have been published, both from respiratory failure. There was a female preponderance of cases in attack of 2-5:1 and in the latent cases of 1-5:1 suggesting hormonal provocation in the uncovering of the disease. Drugs were implicated as precipitating 54 per cent of acute attacks and in 34 per cent of cases, these were barbiturates. This study demonstrates the reduction in activity of coproporphyrinogen oxidase in the haem biosynthetic pathway and the elevation of delta-aminolaevulinic acid synthase in the peripheral blood. These features, together with the typical abnormal porphyrin excretion pattern, appear to be diagnostic of hereditary coproporphyria whether in attack, remission, or in the latent form.

5-Aminolevulinate Synthetase↗
PubMed1976

Blood-cadmium in hypertensives and normotensives.

70 hypertensive patients and 70 controls matched for age and sex were investigated for a possible relationship between blood-cadmium and hypertension. No significant differences between the two groups were detected, although the blood-cadmium level was significantly higher in smokers as compared to non-smokers. These data do not support the hypothesis that cadmium is involved in the development of hypertension in man.

Antihypertensive Agents↗
PubMed1976

Blood-lead and hypertension.

Blood and tap-water lead levels were examined in 135 hypertensives and 135 age and sex matched normotensives. Among male hypertensives there was a significant excess of cases with high blood-lead levels and a similar but statistically non-significant trend was found amongst female hypertensives. A positive correlation was found between blood-lead and tap-water lead. It is concluded that in the West of Scotland high blood-pressure is associated with high blood-lead levels, which might explain the high prevalence of cardiovascular disease in the area.

Blood Pressure↗
PubMed1976

Properties of enzymes from Clostridium thermoaceticum and Clostridium formicoaceticum.

Methylenetetrahydrofolate dehydrogenase from C. thermoaceticum and C. formicoaceticum have been purified to homogeneity and compared. The two enzymes are very similar physically, chemically, and kinetically, but he C. thermoaceticum enzyme has a higher thermostablility, which is an intrinsic property of the protein. Formate dehydrogenase enzymes from both bacteria require selenite and tungstate for formation and these enzymes also appear to have similar properties, although the C. thermoaceticum is stable at 70 degrees C for more than one hour. Acetate kinase from C. thermoaceticum appears to be under metabolic control. It can be concluded that enzymes from C. thermoaceticum, although they are more thermostable, are very similar to corresponding enzymes from mesophilic organisms.

Acetates↗
PubMed1976

The porphyrinogenic effects of kryptopyrrole in the rat and the occurrence of urinary kryptopyrrole in human hereditary hepatic porphyria.

1. Kryptopyrrole (2,4-dimethyl-3-ethyl pyrrole) was shown to elevate the urinary porphyrin excretion and the hepatic content of porphyrins in the rat. The simultaneous administration of sigma-aminolaevulinic acid increased these effects. 2. Kryptopyrrole was present in the urine of patients with hereditary hepatic porphyria, in attack and in remission, but not in those with latent porphyria.

Aminolevulinic Acid↗
PubMed1976

A trial of fenfluramine in the treatment of the chronic alcoholic patient.

In a double blind trial, 50 male chronic alcoholic patients were treated with either fenfluramine in a dose of 60 mg or 120 mg daily, or with identically prepared placebo tablets. Patients were interviewed on admission to the trial and then at four-weekly intervals for a period of one year and blood levels of delta-aminolaevulinic acid dehydratase (ALAD) and gamma-glutamyl transpeptidase (gammaGT) and fenfluramine were determined. The efficacy of fenfluramine at the two dose levels was compared with placebo on the basis of the number of lapses indicated by the clinical history and also by alterations in the biochemical indices. Twenty-seven patients completed the period of observation, there being 9 in each of the three groups. Those receiving 120 mg fenfluramine daily showed significantly fewer lapses than either of the other two groups (p less than 0-01) on biochemical but not on clinical criteria. Overall assessment revealed that 3 of the 9 patients receiving the high dose of fenfluramine had a good result during the period of the trial, but there were none in the 60 mg group or in those receiving placebo. More extensive trials of fenfluramine in the treatment of chronic alcoholism are indicated.

Administration, Oral↗
PubMed1976

Phase I trial of dianhydrogalactitol administered Iv in a weekly schedule.

Dianhydrogalactitol was given to 28 patients with a variety of advanced solid tumors on a weekly schedule in iv doses ranging from 2 to 80 mg/m2. No significant toxicity was encountered at doses up to 40 mg/m2/week for 4 weeks. At higher doses mild-to-moderate nausea and vomiting and hematologic toxicity were noted. Thrombocytopenia was more common than granulocytopenia and frequently resolved more slowly. No adverse drug-realted effects on liver, renal, coagulation, or cardiac function were seen. Although no patient had significant antitumor response (as strictly defined), objective improvement was noted in two patients, one with hypernephroma and the other with malignant melanoma. for phase II studies, a weekly dose of 70 mg/m2 is recommended for patients with normal hematopoiesis, with reduction by 25% (55 mg/m2) in patients with extensive prior radiation therapy, prior chemotherapy, and/or widespread metastasis to the bone.

Adult↗
PubMed1975

Role of chronic low-level lead exposure in the aetiology of mental retardation.

Water-lead levels were measured in the homes occupied during the first year of life by 77 mentally retarded children aged two to six years and 77 non-retarded matched controls, and in the homes occupied by their mothers during pregnancy. The water-lead content was significantly higher in the retarded group, and the probability of mental retardation was significantly increased when water lead exceeded 800 mug. per litre. Blood-lead levels were also significantly higher in the retarded group. It is concluded that lead contamination of water may be one factor in the multifactorial aetiology of mental retardation and that every effort should be made to reduce the lead content of drinking-water.

Breast Feeding↗
PubMed1975

Cardiac effects of lead in drinking water of rats.

1. There is no known cause for the increased mortality due to ischaemic heart disease in soft water areas. Since the lead concentration of soft water is elevated in houses with lead plumbing, studies have been carried out to determine the effects of lead on the heart of rats. 2. Rats were given drinking water containing lead for 1 year at concentrations similar to those found previously in Glasgow, which has a soft water supply. 3. There was increasing deposition of lead in the heart and a fall in the cardiac levels of the enzymes ferrochelatase and delta-aminolaevulinic acid dehydratase. These changes are maximal after 6 months, when there were marked electron-microscopic changes in the myocardium and myocardial mitochondria. 4. Further studies are needed to determine whether lead is a cause of the increased mortality from ischaemic heart disease in soft water areas.

Animals↗
PubMed1975

Urinary excretion of 17-oxosteroids in hereditary coproporphyria.

1. Urinary 17-oxosteroid conjugates were measured by gas-liquid chromatography in five patients with hereditary coproporphyria. 2. Three patients were in an acute attack and showed significantly increased excretion of sulphate or glucuronide conjugates of aetiocholanolone. There was increased excretion of several other related steroids but no consistent pattern was apparent. 3. In the two patients in remission, excretion of urinary 17-oxosteroids was not increased. 4. The ratio of total urinary aetiocholanolone to androsterone (5beta:5alpha) was found to be significantly elevated for the three patients in an acute attack. Serial measurements were made in two of these patients and showed a highly significant linear correaltion between this ratio and the urinary content of delta-aminolaevulic acid and porphobilinogen. 5. These observations suggest the involvement of the 17-oxosteroids, espically aetiocholanolone, in the pathogenesis of hereditary coproporphyria.

17-Ketosteroids↗