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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 181 records · Page 10Linked to original sources
PubMed1985

The Harderian gland, its secretory duct and porphyrin content in the Plains mouse (Pseudomys australis).

The Harderian gland of the Australian Plains mouse (Pseudomys australis) consists of tubules lined by a single layer of epithelial cells with a surrounding meshwork of myoepithelial cells. The epithelium contains three types of cell. Type I cells, characterised by their many large apical lipid vacuoles, are comparable with cells reported in other rodents. Secretion is exocytotic and, to a lesser extent, apocrine. Type II cells are highly distinctive with extremely large mitochondria arranged in stacks and whorls. Unusually for Harderian glands, these cells possess prominent conventional Golgi complexes and lysosomes. Cytoplasmic 'slashes', possible vacuole-precursors, are also present. Type III cells have few distinguishing features and may be resting cells. They are occasionally binucleate and mitotic figures occur. The gland contains stored porphyrins, chiefly protoporphyrin, in the form of solid intraluminal accretions. There is a marked sex difference, with females having higher levels of porphyrin than males. Among the components of the interstitial tissue are mast cells, plasma cells and porphyrin-containing macrophages. The secretory duct contains large quantities of cell debris, including nuclei, and is lined by columnar cells with single large apical vacuoles. The outer opening of the duct is lined by mucus-secreting cells and stratified squamous epithelium.

Animals↗
PubMed1984

Associated effects of sodium butyrate on histone acetylation and estrogen receptor in the human breast cancer cell line MCF-7.

Sodium butyrate at a concentration of 5mM causes significant hyperacetylation of the core histones in the human breast cancer cell line MCF-7. Histone hyperacetylation was achieved in rapidly-growing cells at 40% confluency after 24 hours in 5mM sodium butyrate. More nearly confluent cells did not reach as high a level of histone hyperacetylation. Upon assaying the estrogen receptors, both cytosolic and KCl-extractable nuclear, we found that butyrate treatment had lowered the estrogen receptor levels in both compartments. To our knowledge this is the first report of an effect of sodium butyrate on estrogen receptor levels.

Acetylation↗
PubMed1984

Sex differences in haem biosynthesis and porphyrin content in the Harderian gland of the golden hamster.

Methods are described for the measurement of seven haem biosynthetic enzymes in Harderian gland tissue from male and female golden hamsters. Sex differences were found in five of the seven enzymes. In each case, female tissue exhibited higher activity than male tissue. These differences in enzyme activity are sufficient to account for the major sex difference in porphyrin content in the Harderian gland of this species.

5-Aminolevulinate Synthetase↗
PubMed1984

Kinetics of lead following intravenous administration in man.

Whole body retention of lead (Pb) and lead kinetics in blood, urine and faeces were determined over 2 weeks following i.v. administration of 203Pb-labelled chloride to 2 subjects. Pb was retained with a biological half-life of 73 days (mean). After day 1 Pb excreted in urine and faeces remained fairly constant at 1% and 0.3% of administered dose, respectively. There was a daily loss of 0.5% by other routes. There was a rapid clearance of isotope from plasma with a half-life of 1 min (mean). At 60 min 45% of the administered dose was in erythrocytes; this changed little over the 2 weeks.

Adult↗
PubMed1984

Effect of carbamazepine on haem biosynthesis in man.

The effects of the enzyme-inducing anticonvulsant carbamazepine on haem biosynthesis in healthy male subjects is reported. A dose-dependent increase in the activity of leucocyte delta-aminolaevulinic-acid synthase, the rate-limiting enzyme of haem biosynthesis, was noted following 400 and 600 mg carbamazepine daily in the same eight subjects. This rise was maximal after 1 week's treatment (400 mg: 509% +/- 285 of baseline; 600 mg: 1062% +/- 170 of baseline; P less than 0.01). Values fell from this peak during the second week despite continuing carbamazepine administration. This pattern was confirmed in a further six subjects taking carbamazepine 400 mg daily for 3 weeks in whom more frequent enzyme measurements were made. The activity of uroporphyrinogen-1-synthase in the erythrocyte fell by 10-15% during the treatment periods (P less than 0.01). Uroporphyrin and penta-, hexa- and hepta-carboxylic porphyrins appeared in the urine of all subjects during CBZ therapy. Changes in daily urinary porphyrin and precursor excretion were inconsistent. CBZ is a porphyrinogenic drug which mimics the changes in enzyme activities and urinary porphyrin ester profile found in patients with latent acute intermittent porphyria, who have a genetic deficiency in uroporphyrinogen-1-synthase activity. Leucocyte delta-aminolaevulinic-acid synthase may provide a suitable in vivo system for testing the porphyrinogenicity of drugs in man.

5-Aminolevulinate Synthetase↗
PubMed1984

Reduction in exposure to lead from drinking water and its effect on blood lead concentrations.

The water supply in Ayr (Scotland, UK) was plumbosolvent and many dwellings in Ayr contained lead pipes. In 1981 treatment of the water supply to reduce its plumbosolvency was initiated. Measurements of water and blood lead concentrations were made before and subsequent to the treatment. Most of the measurements made before and after water treatment began were made on water samples from the same dwellings and blood samples from the same women. Water treatment produced a sharp fall in water lead concentrations and a decrease in the median blood lead concentration from 21 to 13 micrograms/100 ml. Two women had higher than expected blood lead concentrations, both these women had been removing old paint. Women who had lead pipes removed from their dwellings all showed substantial decreases in their blood lead concentrations. The curvilinearity of the relation between blood lead and water lead concentrations is confirmed. Even relatively low (less than 40 micrograms/l) water lead concentrations may make a substantial contribution to blood lead concentrations.

Adult↗
PubMed1984

Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

Agranulocytosis↗
PubMed1984

Retinal ganglion cells and axons survive optic nerve transection.

The effects of optic nerve transection on optic axon and retinal cell survival was studied in C57BL/6J mice. The optic nerve was transected either intracranially or intraorbitally . Data are presented which show that an intracranial transection of the optic nerve may be achieved while maintaining the blood supply to the retina. Intraorbital optic nerve transection, however, necessitates destruction of the retinal blood supply. Cell survival in the retinal ganglion cell layer is compared for both transection methods. In addition, electron microscopic evidence is presented which indicates axonal survival in the optic nerve up to at least 90 days following intracranial transection.

Animals↗
PubMed1984

Rapid semiquantitative measurement of total porphyrins in urine and feces by magnetic circular dichroism.

Magnetic circular dichroism is a suitable technique for semiquantitative determination of total porphyrins in urine and feces, being rapid, reliable, and involving little sample preparation. The sensitivity of the assay suffices to distinguish normal from above-normal concentrations of total porphyrins in urine and feces. Results for urine compare well with those obtained by thin-layer chromatography of porphyrin esters (n = 42, r = 0.92) or ion-exchange column chromatography of porphyrin acids (n = 19, r = 0.80).

Chromatography, Ion Exchange↗
PubMed1983

Carbamazepine-induced non-hereditary acute porphyria.

Acute intermittent porphyria has hitherto been recognised as an autosomal dominant inborn error of haem metabolism characterised by a depressed activity of the enzyme uroporphyrinogen I synthase (URO.S). A case of non-hereditary acute porphyria, similar to acute intermittent porphyria, following treatment of epilepsy with carbamazepine is reported. Subsequent measurements of erythrocyte URO.S activity in a group of epileptic patients treated with various combinations of anticonvulsant drugs suggest that carbamazepine exerts a direct suppressant effect on URO.S in addition to its indirect enzyme-inducing properties.

5-Aminolevulinate Synthetase↗
PubMed1983

The Harderian gland, its secretory duct and porphyrin content in the mongolian gerbil (Meriones unguiculatus).

The Harderian gland, its secretory duct and porphyrin content were examined in the mongolian gerbil (Meriones unguiculatus). The gland consisted of tubules lined by a single layer of epithelial cells and a myoepithelial network. The tubule cells were often binucleate and possessed lipid vacuoles in the apical half of the cell, a corona of granular endoplasmic reticulum surrounding the nucleus, and cytoplasmic 'slashes'. The latter are probably derived from dense membranous couplets and may be precursors of the lipid vacuoles. Holocrine and merocrine secretion was observed. Interstitial cells included plasma cells, mast cells and (predominantly) melanocytes which render the gland black. The gland was surrounded by a collagen capsule and an outer layer of highly attenuated (possibly endothelioid) cells. Within the gland, the secretory duct was lined by a single layer of normal tubule cells. Outside the gland, the duct enlarged to form an ampulla, from which clefts led off to deep crypts. The ampulla and clefts were lined by cells with small dense apical granules and stubby microvilli; some possessed lipid vacuoles. The crypts were lined by serous cells with active Golgi regions. At the duct opening, ampullary cells became squamous and goblet cells occurred. Geometric crystalloid deposits (with a layered structure of 7.6 nm periodicity) occurred at cleft-crypt junctions. Islets of extra-glandular ductal tissue were occasionally found within the gland. Porphyrins were detectable both by chemical assay and fluorescence microscopy. There was a trend for female glands to have a higher content than males. Solid intraluminal accretions of porphyrin and/or lipid were present.

Animals↗
PubMed1983

Early-onset chronic renal failure as a complication of acute intermittent porphyria.

In a retrospective survey of patients who have had a proven attack of acute intermittent porphyria (AIP) in the West of Scotland a highly significant association (p less than 0.001) was observed between AIP and the development of early-onset chronic renal failure. Six patients with AIP and chronic renal failure arising in early middle-age are described. As no other cause could be attributed to the renal failure three possible causal links between these two conditions were considered, namely, enhanced susceptibility to analgesic nephropathy, porphyria-induced hypertension, and nephrotoxic effects of porphyrins and their precursors. We suggest that porphyria-induced hypertension is the most important factor in causing early-onset chronic renal failure in acute intermittent porphyria.

Acute Disease↗
PubMed1982

Guidelines for drug prescription in patients with the acute porphyrias.

Certain drugs are well known to cause acute neurological crises in patients with hereditary coproporphyria, variegate porphyria and acute intermittent porphyria. Guidelines for drug therapy have been provided in this article, particular attention being paid to the manner in which the porphyrogenicity or safety of a drug has been assessed and providing full references to the original reports to allow further research if necessary.

Acute Disease↗