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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 199 records · Page 11Linked to original sources
PubMed1982

Studies of nicotinamide adenine dinucleotide methemoglobin reductase activity in a Jewish population.

In the original study of the deleterious effects of oxidant drugs on persons heterozygous for nicotinamide adenine dinucleotide reductase (NADH MetHb R) deficiency, several Jewish physicians used as controls had decreased enzyme activity. We collected blood samples from 555 Jewish persons to 1) estimate the heterozygote frequency for NADH MetHb R deficiency; and 2) determine if external variables such as age, gender, and ingested medications may alter the NADH MetHb R activity and thereby alter estimates of heterozygosity. Two persons possibly heterozygous for the deficiency were identified (carrier incidence = 1/309,000 jewish births). A difference in enzyme activity was found between males and females (P less than 0.03). We have examined the influence of the mean red cell age on the activity of erythrocyte NADH MetHb R and found it not to be materially influenced by mean red cell age; thus the possible intersex differences of mean red cell age cannot explain this observation. No significant difference (P greater than 0.1) was seen between persons ingesting the following drugs and those not: Dilantin; antidepressants/sedatives; cardiac, antineoplastic, or antigout/antiinflammatory drugs; thyroid supplements, estrogen-containing preparations, and antihistamines. NADH MetHb R activity did not correlate with age or spontaneous abortion. We conclude that heterozygosity for NADH MetHb R deficiency is not prevalent among Ashkenazic Jewish persons, and that external variables should be considered to ensure accurate interpretation of NADH MetHb R activity for correct estimation of heterozygosity.

Adolescent↗
PubMed1982

Severe Fletcher factor (plasma prekallikrein) deficiency with partial deficiency of Hageman factor (factor XII): report of a case with observation on in vivo and in vitro leukocyte chemotaxis.

A case of cross-reacting material-negative Fletcher trait with additional partial deficiency of Hageman factor (HF, Factor XII) is described. Although the patient presented with a recent history of frequent epistaxis, he had no other personal or family history of a tendency toward bleeding or infection. Similar to other cases of Fletcher trait, his plasma showed a markedly prolonged partial thromboplastin time which could be corrected by prolonged incubation with the surface-activator kaolin. Surface-induced fibrinolysis, amidolysis of alpha-N-benzoyl-proline-L-phenylalanine-L-arginine-p-nitroanilide, and cold-promoted enhancement of factor VII activity, reactions requiring the presence in the plasma of fletcher factor (prekallikrein), in addition to Hageman factor and Fitzgerald factor (high-molecular weight kininogen), were also defective. In vivo chemotaxis of polymorphonuclear leukocytes and monocytes (Rebuck's skin window technique) in response to skin abrasions was defective, but was normal when diphtheria-tetanus toxoid was also applied. In vitro leukocyte chemotaxis (Boyden chamber technique) in response to normal or patient's own serum activated with zymosan was normal. Together with previous observations that kallikrein generated chemotactic activity, possibly via activation of C5, the present observations suggest that prekallikrein activation may be important for in vivo leukocyte chemotactic response to skin abrasion. The inheritance of Fletcher trait in this patient is unclear.l Although the father was an apparent heterozygote, the mother was completely normal for Fletcher factor procoagulant activity and antigen. The mild Hageman factor deficiency in the patient did not contribute significantly to the plasma defects described and was likely inherited from the father who had a low HF procoagulant activity.

Blood Coagulation↗
PubMed1982

Screening for latent acute intermittent porphyria: the value of measuring both leucocyte delta-aminolaevulinic acid synthase and erythrocyte uroporphyrinogen-1-synthase activities.

Acute intermittent porphyria (AIP) is an autosomal dominantly inherited disorder of haem biosynthesis characterised by reduced activity of the enzyme uroporphyrinogen-1-(URO) synthase and compensatory increased activity of the rate controlling enzyme delta-aminolaevulinic acid (ALA) synthase. Subjects with the disorder should be identified as they are at risk of developing severe porphyric attacks if exposed to a variety of drugs or chemicals. We have assessed the value of measuring the activities of ALA synthase and URO synthase in peripheral blood cells as a means of identifying latent cases in affected families. In AIP subjects, ALA synthase activity was increased and URO synthase decreased compared to controls, through there was considerable overlap between the two groups when either enzyme was examined alone. When both enzymes were examined together, all but one of the 19 AIP patients had both increased ALA synthase activity (greater than 250 nmol ALA/g protein/h) and reduced URO synthase activity (less than 25.1 nmol URO/l RBC/h), whereas none of the 62 controls showed this enzyme pattern. Examination of 35 asymptomatic first degree blood relatives of AIP patients showed that 17 (49%) had the porphyric enzyme pattern with no sex bias. The combined study of these two enzymes permits accurate detection of latent cases of AIP and confirms its autosomal dominant inheritance.

5-Aminolevulinate Synthetase↗
PubMed1982

Some studies of maternal and infant lead exposure in Glasgow.

In two studies in the city of Glasgow, 236 mothers and their newly born infants and 117 mothers and their 6-weeks old children's environmental lead exposure were examined. In both studies blood lead concentrations were found to correlate significantly with the cube root of the domestic water lead concentrations. In the first study, multiple regression analyses of maternal blood lead and cord blood lead concentrations on other variables showed a significant negative correlation with gestational age. It was also noted that there was an annual fluctuation in maternal blood lead concentration with highest values in the autumn. In the second study, similar relationships were found. Although there was no association between blood lead and sex, age, place of birth or feeding method, as in the previous study, a significant association between social class and blood lead was found. This could be explained on the basis of the significant correlation between water lead and social class. In those mothers who breast fed, breast milk lead concentrations were found to correlate significantly with blood lead concentrations where breast milk lead was around one tenth of blood lead concentration. These studies emphasise the importance of water lead in the economy of environmental lead exposure to mothers and their unborn and newly born infants.

Adolescent↗
PubMed1982

Assessment of lead intakes and dose-response for a population in Ayr exposed to a plumbosolvent water supply.

1 Dietary lead intakes, blood lead concentrations and water lead concentrations were measured and their relationships investigated for 31 adults and 11 infants living in dwellings in Ayr with lead plumbing. 2 For adults, some lead intakes were found to be higher than the provisional tolerable weekly intake for lead, and for infants most of the intakes were high. 3 A cube root relationship fitted the data on blood lead versus water lead better than a linear relationship. Similarly, blood lead varied with the cube root of weekly dietary lead intake. 4 These cube root equations provided a means of estimating the impact on blood lead concentrations of exposure to lead from food and water. If cube root relationships correctly describe the association between these parameters, then the curve fitted to the results for adults indicates that the contribution to the blood lead concentrations from sources other than the diet and water was relatively small.

Adult↗
PubMed1982

Cholangiocellular carcinomas induced in Syrian golden hamsters administered aflatoxin B1 in large doses.

The hepatocarcinogenicity of aflatoxin B1 (AFB1) was compared in male Syrian golden hamsters and inbred F344 rats. AFB1 was administered by gavage 5 days/week for 6 weeks at doses of 1 and 2 mg/kg body weight/day to rats and hamsters, respectively; rate did not survive beyond 3 weeks with doses of 2 mg/kg/day. After 6 weeks the animals either received no further treatment or were given 0.1% phenobarbital sodium in the drinking water. ATPase-deficient foci of hepatic parenchymal cells, neoplastic nodules, and hepatocellular carcinomas were observed in liver sections from AFB1-treated rats killed at 6, 14, or 23 weeks; they were not seen in sections from AFB1-treated hamsters killed at 6, 14, or 46 weeks. Each of the 50 AFB1-treated rats developed hepatocellular carcinomas by 46 weeks; many also had cholangiocarcinomas and mixed hepatocellular-cholangiocellular carcinomas. Hepatocellular carcinomas were found in only 2 of 49 AFB1-treated hamsters by 78 weeks. At this time cholangiocarcinomas were found in 15 hamsters, and microscopic cholangiomas were seen in all of the livers. Compared to the rat, the hamster was resistant to the hepatotoxic and hepatocellular carcinogenic effects of AFB1.

Adenoma, Bile Duct↗
PubMed1982

Studies of lead and cadmium exposure in Glasgow, U.K.

Domestic water and whole blood samples were collected early in 1981 from two hundred volunteers living in the Glasgow area of Scotland, U.K. The concentration of lead in the water and blood samples, and of cadmium in the blood, was measured. The blood lead and cadmium concentrations were compared to those obtained in the Survey of 1979. There has been a fall in blood lead concentrations since the 1979 Survey. In contrast, the blood cadmium levels had remained similar. This diminution in blood lead concentration is attributed to a fall in water lead concentration caused by raising the pH of the water supply in the Glasgow area. The main determinant for cadmium in blood appears to be cigarette smoking habits, which had not changed.

Adolescent↗
PubMed1982

Mast cells in the hamster Harderian gland: sex differences, hormonal control and relationship to porphyrin.

The Harderian gland of the female golden hamster contains an average of forty times more mast cells in the interstitial tissue than the male gland. A similar sex difference occurs in the connective tissue capsule of the gland. Mast cell numbers in the male Harderian gland increase greatly between two and five months after castration, reaching levels comparable to those found in the female. This postcastrational rise in mast cell numbers is prevented by androgen administration; furthermore, if mast cell numbers are allowed to increase in castrates, subsequent androgen administration will reverse the rise. There is no obvious relationship between mast cell numbers in the Harderian gland of the female hamster and the porphyrin content of the gland.

Androgens↗
PubMed1981

An insulin effect on cytoplasmic estrogen receptor in the human breast cancer cell line MCF-7.

It has recently been reported (Horwitz, K. B., Zava, D. T., Thilagar, A. K., Jensen, E. M., and McGuire, W. L. (1978) Cancer Res. 38, 2434-2437) than the human breast cancer-derived cell line MCF-7 from EG&G Mason Research Institute contains no 8 S and very little 4 S cytoplasmic estrogen receptor. Even so, we have found significant levels of cytoplasmic estrogen receptor in MCF-7 cells from this source. The receptor was found at a maximum level of 132 fmol/mg of cytoplasmic protein, and had an apparent dissociation constant at 30 degrees C of 7.3 X 10(-10) M and at 4 degrees C of 1.2 X 10(-10) M. In sucrose gradients without KCl, the receptor migrated at 6-7 S, and with 0.4 M KCl, at 3-4 S. The receptor was specific for estrogen, in that a 100-fold excess of diethylstilbestrol eliminated binding of radiolabeled estrogen, whereas hydrocortisone, aldosterone, progesterone, and testosterone had no effect. It was further demonstrated that at least part of the reason for the discrepancy between our data and those of Horwitz et al. is that the high insulin level (10 microgram/ml) used by Horwitz et al. dramatically lowers the assayable level of receptor. These results may have important implications for steroid receptor assays in other cell lines in tissue culture and in human breast cancer patients as well.

Breast Neoplasms↗
PubMed1981

Abnormal haem biosynthesis in chronic alcoholics.

The activities of six of the enzymes of haem biosynthesis have been examined in eleven chronic alcoholics admitted to hospital for alcohol withdrawal. The mitochondrial enzymes delta-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leucocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen-1-synthase and uroporphyrinogen decarboxylase in peripheral erythrocytes. Compared with control subjects the activity of the initial and rate controlling enzyme of the pathway, ALA synthase, was increased (P less than 0.01) and the activities of ALA dehydratase and uroporphyrinogen decarboxylase depressed (P less than 0.01, P less than 0.02 respectively) on the day after admission but all returned to normal by the tenth to twentieth days after alcohol withdrawal. This stimulation of ALA synthase and inhibition of uroporphyrinogen decarboxylase explains the mechanism by which chronic alcohol ingestion may precipitate cutaneous hepatic porphyria. Two of the alcoholics were anaemic without evidence of haematinic deficiency and this was associated with depressed ferrochelatase activity and iron and porphyrin accumulation. The anaemia and related biochemical abnormalities in these two subjects were all corrected with alcohol withdrawal. It is proposed that inhibition of ferrochelatase activity is the biochemical basis of alcohol related sideroblastic anaemia.

5-Aminolevulinate Synthetase↗
PubMed1981

Quantitative analysis of the time-dependent development of glucose-6-phosphatase-deficient foci in the livers of mice treated neonatally with diethylnitrosamine.

The development of glucose-6-phosphatase (G-6-Pase-)-deficient hyperbasophilic foci was analyzed at 4-week intervals in the livers of CD-1 and C57BL/6J x C3H/HeJ F1 (hereafter called B6C3F1) mice given a single i.p. injection of diethylnitrosamine (DEN) (0.1, 0.2, or 0.4 mumol/g body weight) within 24 hr after birth. Transections of G-6-Pase-deficient foci of hepatocytes were readily discernible in liver sections of DEN-treated mice of either sex at 8 weeks of age. The size and number of these foci per liver increased with time. The occurrence of G-6-Pase-deficient focus transections with diameters as large as 1 mm coincided with the gross appearance of 1-mm gray-white nodules in the livers of male B6C3F1 mice at 16 weeks of age and in females at 32 weeks of age. Transections of all grossly visible hepatic nodules from male and female mice were G-6-Pase deficient and hyperbasophilic; the great majority were diagnosed as mouse hepatomas type A. After a single neonatal dose of DEN, the number and rate of growth of the G-6-Pase-deficient foci and the incidence and rate of appearance of gross hepatomas were greater in the liver of male than in those of female mice. In contrast, the average numbers of G-6-Pase-deficient foci in the livers of male and androgenized female B6C3F1 mice at 36 weeks of age were approximately equal and about twice that observed for the livers of DEN-treated female controls. Quantitation of carcinogen-induced histochemically detectable foci and hepatomas as a function of time provides a useful tool for the analysis of initiation and promotion in the mouse liver.

Age Factors↗
PubMed1981

Treatment with haematin in acute hepatic porphyria.

We report our experience with intravenous haematin in the treatment of 13 attacks of acute porphyria in eight patients. Seven patients had acute intermittent porphyria and one variegate porphyria. Peripheral neuropathy was a feature of nine of the attacks and in two the neuropathy necessitated assisted ventilation. The haematin lowered the urinary excretion of porphyrins and precursors in all patients by approximately 50 per cent of the pre-haematin values. It also repressed the activity of delta-aminolaevulinic acid synthetase, the rate-controlling enzyme of haem biosynthesis, in peripheral leucocytes in seven of the nine patients in whom it was monitored. The clinical response was less consistent, with clinical improvement accompanying only half of the courses. The two patients with respiratory paralysis died. There was localized phlebitis at the injection site following five of the courses but no other side-effects were noted. Previously published reports of haematin therapy for acute porphyria are reviewed. These consist of 45 courses in 32 patients. Biochemical improvement was a consistent finding. Clinical response has been less consistent. Twenty-four of the courses were associated with sustained improvement, ten with temporary improvement--relapse occurring within two to 14 days (three fatal). In eleven there was no improvement and three died.

5-Aminolevulinate Synthetase↗