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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

341 records · Page 19Linked to original sources
PubMedDate not supplied

Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA.

Direct cDNA sequencing has been performed on asymmetrically amplified transcripts from the human porphobilinogen deaminase gene. Lymphocytes from 30 patients with acute intermittent porphyria were the source of mRNA; of the seven separate point mutations detected, three were silent, whereas four resulted in amino acid changes. Three of these changes involved highly conserved amino acids, and the remaining one a conserved charge. One of these mutations was predicted to cause structural alterations in the protein product. The application of this method to affected families allows the direct identification of these heterogeneous mutations, thus permitting the unequivocal detection of carriers.

Base Sequence↗
PubMedDate not supplied

The effect of carbon monoxide upon erythrocyte delta-aminolevulinicacid dehydratase activity.

The activity of the delta-aminolevulinicacid dehydratase enzyme in the second reaction of the heme biosynthetic pathway has been determined in human blood in the presence of varying concentrations of carboxyhemoglobin. In vivo and in vitro carbon monoxide exposure causes a consistent, but small, significant diminution of activity. At concentrations of carboxyhemoglobin likely to be found in vivo it is unlikely to significantly influence the use of this enzyme as a measure either of lead exposure or of ethanol consumption.

Cadmium↗
PubMedDate not supplied

Occupational lead exposure and renin release.

Hypertension may result from chronic lead exposure. Lead poisoning arising from "moonshine whiskey" drinking has been associated with a rise in plasma renin activity. In the present study, plasma renin concentration following intravenous administration of frusemide was measured in eleven subjects with moderate or severe lead poisoning of industrial origin. The results were compared with those obtained for seven normal, control subjects. There was no significant difference in response obtained in the two groups. Industrial lead poisoning does not appear to affect renin release. The combined insult of lead and alcohol may explain the findings in the previous study.

Adolescent↗
PubMedDate not supplied

Reversibility of the chronic effects of di(2-ethylhexyl)phthalate.

Fischer-344 rats treated with 12,500 ppm (728 and 879 mg/kg/d for male and females, respectively) and B6C3F1 mice treated with 6,000 ppm (1,227 and 1,408 mg/kg/d, respectively) di(2-ethylhexyl)phthalate (DEHP) in the diet for 78 weeks were allowed to recover for an additional 26 weeks on control diet. Blood was analyzed at weeks 78 and 104 from 10 animals per sex per group; animals were sacrificed at weeks 79 and 105 for histopathologic examination. The results are compared with data from animals continuously exposed to these dietary levels for 104 weeks (10, 11). Body weights and food consumption were measured monthly. BUN, albumin, and globulin that were significantly different for rats exposed to DEHP throughout 104 weeks, were comparable to controls for the recovery group. Reversibility of chronic effects on erythrocyte count, hemoglobin, and hematocrit values was apparent only for female rats. Chronic exposure demonstrated effects on liver, kidney, and testes weights. All organ weight effects except for testes for the Recovery group of rats, and all organ weight effects for mice, were reversible. Pigmentation of Kupffer cells and renal tubules present in chronically treated rats were not observed for the Recovery group. Lesions in the testes and pituitary gland were not reversible in rats. This may be a reflection of the senescence of the hypothalamic-gonad axis in rats. Cessation of exposure for mice resulted in amelioration of effects in the kidneys, liver, and testes. The extent of reversibility suggests that many chronic effects may be associated with a metabolic phenomenon such as peroxisome proliferation, which also reverted to control levels after 26 weeks of recovery.

Administration, Oral↗
PubMedDate not supplied

Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria.

We have screened the hydroxymethylbilane synthase cDNAs of 3 patients from 2 families suffering from acute intermittent porphyria (AIP) from Scotland and South Africa using heteroduplex and chemical cleavage of mismatch analyses. Direct sequencing was used to characterise the mutations. The two novel mutations identified were a missense mutation at nucleotide position 64 in exon 3 (R22C) and a single base-pair deletion in exon 15. These mutations are predicted to affect the normal function of the enzyme and, therefore, are expected to be the primary cause of disease in these patients.

Female↗
PubMedDate not supplied

Phase II study of alternating cytoreductive and cycle-active combination chemotherapy for metastatic breast cancer.

Nineteen females with metastatic breast cancer (73% with visceral disease) treated with cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) cytoreduction followed by, and then alternated with, an intensive "cycle-active" regimen were evaluable. Sixteen of the 19 (84%) patients responded to CAF prior to initiation of the cycle-active regimen, and median remission duration for CAF responders was 50 weeks. The regimen was tolerable and the remission rates and durations were at least as good as those seen with CAF alone. This regimen is now being compared with CAF in a randomized trial of the Southeastern Cancer Study Group.

Adult↗
PubMedDate not supplied

A prospective study of the neurological effects of lead in children.

In the past three 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 studies in 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 151 children subdivided into three groups according to the level of lead exposure during early in utero development as assessed by maternal blood lead concentration and water lead exposure in early pregnancy. Data amassed to date include measurement of psychometric function and postnatal development at the ages of 1 and 2, 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.

Child↗
PubMedDate not supplied

The acute porphyrias.

The porphyrias are a heterogeneous group of rare inborn errors of metabolism caused by inherited enzyme defects in the haem biosynthetic pathway, resulting in overproduction of porphyrins. The porphyrias can be distinguished biochemically but may be difficult to differentiate clinically. Considerable advances have been made in the understanding of the enzymology and molecular biology of the porphyrias. The acute attack of porphyria may be a life-threatening condition, and an understanding of its many precipitating factors, clinical features and management is of importance in a disease with a significant mortality.

Acute Disease↗