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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 127 records · Page 7Linked to original sources
PubMed1989

Cytoplasmic retinoid-binding proteins and retinoid effects on insulin release in RINm5F beta-cells.

Vitamin A (retinol) is required for insulin secretion, and retinoic acid substitutes for retinol in this function. To determine if retinol acts at the beta-cell level, we assayed beta-cells of the rat insulinoma (RINm5F) line for cytosolic retinol- and retinoic acid-binding proteins (CRBP and CRABP) by radioimmunoassay (RIA) and [3H]retinol and [3H]retinoic acid binding to cytosol extracts. Furthermore, we tested whether insulin release from cells was affected by addition of retinol or retinoic acid to culture medium. RINm5F cells were grown to near confluence before assay of CRBP and CRABP. Scatchard analysis showed the Kd for retinol to be approximately 6 nM at a level of 4.5 pmol/mg protein or 300,000 sites/cell. Sucrose density-gradient assay showed single discrete peaks migrating at 2S for both retinol and retinoic acid. RIA of whole-cell extracts showed CRBP and CRABP levels of 5.27 +/- 0.41 and 2.95 +/- 0.75 pmol/mg protein, respectively. Retinol (1.75 microM) and retinoic acid (0.175 and 1.75 microM) increased KCl-induced insulin release. Considered together, the presence of CRBP and CRABP in a beta-cell line and the increase in KCl-induced insulin release by retinol and retinoic acid are consistent with the idea that retinol has a functional role in insulin secretion and suggest a potential mechanism of action at the beta-cell level similar to that observed in other retinoid-responsive cells.

Animals↗
PubMed1989

Action of lead on neurotransmission in rats.

1. The neurotoxic effect of lead on the catecholaminergic and cholinergic nervous systems has been investigated using a rat model of lead exposure. 2. This model of lead exposure resulted in significant quantities of lead accumulating in the blood, brain and femur of the lead-exposed animals. 3. The biochemical effect of lead on brain neurochemistry was dependent on the degree and duration of lead exposure. However, the data points to a selective action of lead, with the midbrain and diencephalon being prime targets while very few lead-related alterations were observed in the cerebellum or the telencephalon. 4. Within the catecholaminergic nervous system, lead exposure resulted in alterations in the concentrations of the transmitters, noradrenaline and dopamine, in addition to changes in the activities of the enzymes tyrosine hydroxylase and phenylethanolamine-N-methyl transferase. The activity of the cholinergic biosynthetic enzyme, choline acetyltransferase was also noted to be altered by lead exposure.

Animals↗
PubMed1989

Stereotactic craniotomy: methods and results using the Brown-Roberts-Wells stereotactic frame.

Combining the power of stereotactic precision with open craniotomy in a stereotactic craniotomy technique decreases surgical time, morbidity, and postoperative hospitalization. Indications for its use are deep intrinsic masses 3.5 cm or less in diameter; small, superficial lesions otherwise difficult to localize; and lesions associated with motor, visual, or speech areas. Using the standard Brown-Roberts-Wells system allows a) precisely planned cortical entries, b) gross total lesion excisions under direct vision, c) use of probe-guided resection margins, d) small craniotomies through linear incisions, and e) use of local anesthetic alone for resections. The method and results of this universally available and relatively inexpensive technique are discussed in reference to 20 patients.

Adolescent↗
PubMed1988

The effects of chronic carbamazepine treatment of haem biosynthesis in man and rat.

The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p less than 0.001) and ALA-dehydratase activity was reduced by 37% (p less than 0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (rs = -0.45; p less than 0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (both p less than 0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.

5-Aminolevulinate Synthetase↗
PubMed1988

Effects of low-level lead exposure on 24 h activity patterns in the mouse.

Spontaneous activity of male mice chronically exposed to lead acetate or sodium acetate was tested for periods of 24 h in their home cages and normal housing groups. Animals receiving 0.25% lead acetate showed significantly higher levels of spontaneous activity than did distilled water controls during the early part of the dark phase in two experiments, and significantly lower activity levels during the latter part. Mice receiving 0.025% lead acetate were also significantly more active than controls early in the dark phase, and either significantly higher or no different from controls latterly. Animals receiving 0.025% sodium acetate were significantly less active than controls early in the dark phase, but later were equally active. Weight loss in lead-treated animals was variable and not correlated with changes in activity levels.

Acetates↗
PubMed1988

Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient.

The short-term effects of sodium valproate (VPA) on haem biosynthesis were assessed in a placebo-controlled crossover trial in eight healthy male subjects who ingested VPA 500 mg t.i.d. and matched placebo for 5 days. All showed augmented activity of leucocyte 5-aminolaevulinate synthase (ALA-S) activity, the rate-limiting enzyme of the haem biosynthetic pathway, following 3 and 5 days of VPA treatment (P less than 0.001). This was accompanied by increased urinary excretion of 5-aminolaevulinic acid (ALA; P less than 0.02) and total porphyrins (P less than 0.01). Mean (+/- SD) total VPA concentrations on day 3 (89 +/- 16 mg 1-1) and day 5 (91 +/- 22 mg 1-1) were within the target range for the drug. The long-term effects of VPA administration were examined in epileptic patients on established monotherapy. Leucocyte ALA-S activity (P less than 0.001), and daily urinary excretion of porphobilinogen (P less than 0.01) and total porphyrins (P less than 0.01) were all higher than in age-matched controls. No significant differences in erythrocyte ALA-dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase activities were found between the groups. These data suggest that VPA is porphyrinogenic in man and cannot be recommended as safe for seizure management in the porphyric patient.

5-Aminolevulinate Synthetase↗
PubMed1988

The effects of age on the structure and porphyrin synthesis of the harderian gland of the female golden hamster.

The effects of age on structure and porphyrin synthesis were examined in the Harderian gland of the female golden hamster. An age range of 2-24 months was examined. Porphyrin enzyme activity reached a peak at 6 months and then declined; the porphyrin content of the gland (as determined both by biochemical assay and by the number of visible porphyrin accretions) also declined from 6 months. Mast cells, found in large numbers in the actively synthesising female gland, declined with age. Conversely, tubule epithelial cells with large lipid vacuoles (Type II cells--characteristic of the non-synthesising male gland) increased in frequency. There was considerable evidence of degenerative changes in gland structure with age. These included thinning of the tubule walls, invasion of the tubule lumen by neutrophils and the appearance of porphyrin stores within the interstitium of the gland. The latter were either large accretions surrounded by foreign body giant cells, or smaller deposits within individual free macrophages. Changes may be the result of ageing itself, of hormone insufficiency in post-reproductive senescence or inflammatory processes.

Aging↗
PubMed1988

A modified technique for cervical facet fusions.

Posterior facet fusion of the cervical spine has been described in the literature as a method of obtaining fusion when posterior elements are deficient because of previous laminectomy or trauma. The technique, as originally described, includes anchoring autologeneic struts of corticocancellous bone to the cervical spine with wires passed through drill holes in the inferior articular facets around the struts of bone graft. When long facet fusions are required, however, it may be impossible to obtain adequate length and shape of the grafts to bridge the desired fusion area. A technique is described that eliminates this problem by substituting thin Harrington compression rods for the autologeneic corticocancellous struts, and using cancellous and corticocancellous bone graft to achieve fusion.

Adolescent↗
PubMed1987

Effect of haem arginate therapy on porphyrin metabolism and mixed function oxygenase activity in acute hepatic porphyria.

The effect of haem arginate on porphyrin metabolism and haemoprotein function was studied during seven attacks of acute hepatic porphyria in 5 patients. In each attack it greatly reduced the overproduction of porphyrin precursors and repressed the overactivity of the rate-controlling enzyme of haem synthesis delta-aminolaevulinic acid (ALA) synthase measured in leucocytes. Antipyrine clearance, an index of the oxidative function of cytochromes P-450, the major group of hepatic haemoproteins, was increased during haem therapy. Thus, haem arginate not only suppresses the overproduction of haem precursors but also improves hepatic oxidative metabolism in acute porphyria.

Acute Disease↗
PubMed1987

Progestin stimulation of lactate dehydrogenase in the human breast cancer cell line T-47D.

We have previously reported that physiological levels of progestins alone stimulate lactate dehydrogenase in a dose-responsive manner in the progesterone-receptor-rich human breast cancer cell line T-47D. Using isozyme electrophoresis, we have not found that lactate dehydrogenase isozyme 5 is the only isozyme detectable in these cells, as has been reported for other human breast cancer cells in long-term tissue culture. Upon treatment with progestins, isozyme 5 remains the only isozyme detectable. T-47D cells were plated in charcoal-stripped serum-containing medium and grown for 2 days before treatment with progestin. Lactate dehydrogenase stimulation then plateaued after around 2-3 days of treatment with progestin and was maintained until around day 5, following which a decline in enzyme activity occurred. The effect is specific for progestins, and inhibited by the anti-progestin RU-38486 (17 beta-hydroxy-11 beta-(4-dimethyl-aminophenyl-1)-17 alpha-(prop-1-ynil)-estra-4,9-dien-3-one). Experiments using actinomycin D and cycloheximide suggests that the effect is dependent on RNA and protein synthesis, respectively. Lactate dehydrogenase stimulation occurs regardless of the presence of the estrogenic pH indicator Phenol red, and of whether it was analyzed per mg DNA or per mg protein.

Breast Neoplasms↗
PubMed1987

Progestin effects on growth in the human breast cancer cell line T-47D--possible therapeutic implications.

In order to determine growth effects of the progestin R5020, (promegestone), we have utilized the progesterone-receptor rich human breast cancer cell line T-47D, growing the cells in the absence of the pH indicator phenol red, which has recently been found to be estrogenic. In contrast to reports on cells grown in the presence of phenol red, we find that promegestone alone, at physiological progestin concentration, significantly stimulates growth. Estradiol alone, at physiological concentration, stimulates growth much more. Promegestone in combination with estradiol is antiestrogenic for growth; that is, it significantly decreases the growth stimulatory effect of estradiol. These results raise the possibility that estrogen receptor and progesterone receptor-rich breast cancer patients might benefit more from a combination of anti-progestin and anti-estrogen therapy than from anti-estrogens alone.

Breast Neoplasms↗
PubMed1987

The effects of chronic lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery occlusion or by noradrenaline in anaesthetised rats.

The aim of this study was to investigate whether chronic (3 months) lead (250 or 1000 ppm), administered as lead acetate in the drinking water, commencing either after weaning (in normotensive or spontaneously hypertensive male rats) or from conception (normotensive rats only) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or by noradrenaline. Treatment with lead alone had no marked effect on the arrhythmias elicited by either method. Spontaneously hypertensive rats treated with either dose of lead exhibited more ectopic beats following coronary artery occlusion than normotensive rats but not more than those observed in control spontaneously hypertensive rats. An enhanced arrhythmogenic effect of noradrenaline was observed only in hypertensive rats administered 250 ppm lead. Both doses of lead accelerated the development of high blood pressure and in normotensive rats the higher dose also resulted in an elevated pressure. Following administration of lead, blood lead concentrations were elevated to 0.96 and 2.11 mumol l-1 after 250 and 1000 ppm, respectively. Accumulation of lead in heart and bone was also observed. We conclude that chronic exposure to these concentrations of lead, when combined with high blood pressure, slightly enhances the susceptibility of the heart to arrhythmias induced by myocardial ischaemia.

Anesthesia↗