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Biomedical subjects

M Webb

Publications and source records attributed to M Webb.

At least 91 records · Page 5Linked to original sources
PubMed1987

Metallothionein in regeneration, reproduction and development.

The presence of metallothionein in high concentrations in the livers of foetuses and/or newborn of all mammalian species thus far investigated is well-established, explanations of why it is there and what it does are hypothetical. This paper attempts to distinguish between fact and fiction and to evaluate critically the evidence for and against the various functional roles that have been proposed for metallothionein in liver regeneration and in mammalian reproduction and development.

Animals↗
PubMed1987

The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule.

Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s.c.) injection of 3 mumol CdCl2/kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06-5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5-10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s.c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Teratogenicity of ionic cadmium in the Wistar rat.

In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i.v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25-2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i.p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.

Animals↗
PubMed1987

Huntington's disease: correlations of mental status with chorea.

We have studied 10 Huntington's disease (HD) outpatients to investigate the relationship between chorea and the psychiatric manifestations of this disease. We used neuropsychological tests sensitive to memory and diffuse cerebral dysfunction and a new, simple, objective test of chorea to study the relationship between chorea and dementia. Using SADS/DSM-III diagnoses, we replicated previous findings of the high prevalence of psychiatric disorders associated with HD. A new finding in this study was the strong relationship between the severity of chorea and that of dementia, particularly regarding memory loss. Implications of this finding are discussed in light of the neuroanatomy of the basal ganglia and frontal lobes.

Adult↗
PubMed1987

The effects of treatment with selenite before and after the administration of [75Se]selenite on the exhalation of [75Se]dimethylselenide.

The exhalation of dimethylselenium, as indicated by the respiratory loss of 75Se from injected Na75SeO3, depends not only on the dose, but also on previous exposure. Three days pretreatment with 1.2 mumol/100 g unlabelled selenite increased exhalation of 75Se from 0.1 or 1.2 mumol/100 g Na2 75SeO3 and decreased the retention of 75Se in blood and liver from the higher dose. Similarly the injection of 1.2 mumol/100 g unlabelled selenite 24 h after the last of 3 daily doses of 1.2 mumol/100 g labelled selenite increased the exhalation of 75Se in the following 24 h period. Thus, pre-exposure to selenium increased the exhalation of 75Se by making a higher proportion of the newly injected dose accessible for methylation. The exhaled dimethylselenide, however, is not derived solely from the injected dose, since in pretreated animals, it is possible to demonstrate exchange between injected and deposited selenium.

Animals↗
PubMed1987

Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--IV. Mechanisms of intestinal copper accumulation.

Copper-67, administered either parenterally or via the maternal milk, accumulates principally in the intestine and liver of the 6-day-old pup. Most of the 67Cu in the soluble fraction of the intestine is associated with the heterogeneous Cu-complex, which is located predominantly in the ileum. The rates of uptake and loss of 67Cu in the liver and intestine indicate that enterohepatic circulation of Cu in the neonate is appreciable. Whilst the concentration of Cu in the bile of the 13-day-old pup is high (16-fold greater than that in the adult male rat), translocation of Cu from both the liver and duodenum to the ileum probably occurs via the blood, rather than by the reabsorption of biliary Cu. Although the Cu-complex normally seems to be retained within the distal intestine until the enterocytes are desquamated, Cu in this form is utilized when the Cu-intake of the neonate is restricted.

Animals↗
PubMed1987

Clinical anophthalmos.

We report on 15 patients (10 boys, 5 girls) with clinical anophthalmos. Two of them had bilateral anophthalmos, 10 had systemic anomalies, and six had abnormalities of their remaining eye. Only two appeared to have an associated underlying aetiology. Fourteen patients underwent orbital reconstruction or socket enlargement with varying degrees of success. Our own experience suggests that unnecessary lid procedures should be avoided, but we recommend early prosthetic fittings. We feel that a multidisciplinary approach is necessary to attain useful rehabilitation.

Anophthalmos↗
PubMed1986

The stimulation and inhibition of the exhalation of volatile selenium.

Administration of methylmercury (1.5-24 mumol kg-1; s.c.) to female rats simultaneously with Na2 75SO3 (0.25 or 24 mumol kg-1; s.c.) causes a dose-dependent increase in the exhalation of dimethylselenide. At the low selenite dose level, exhalation of 75Se over a 24 hr period is about fourfold greater after treatment with 24 mumol kg-1 methylmercury than that (approximately 0.75% of the dose) in the controls, but excretion by other routes (urine, faeces) and the liver and kidney contents of 75Se are not affected significantly. At the higher selenite dose level (24 mumol kg-1) exhalation of 75Se is correlated with the log dose of methylmercury. The faecal and urinary excretion remains essentially unaffected, and in rats treated with 24 mumol kg-1 methylmercury the 75Se contents of the liver, kidneys and blood are reduced by 78%, 86% and 18% respectively. The effects of the alkylmercurial are not specific since, at this selenite dose level, ethylmercury increases the exhalation and decreases the liver and kidney contents of 75Se approximately to the same extent as an equimolar dose of methylmercury. In methylmercury-treated and control animals dosed with 24 mumol kg-1 Na 75SeO3 the exhalation of 75Se is inhibited to the same extent by periodate-oxidized adenosine (PAD; 15 mumol kg-1, i.p.) in the first 6 hr. Later inhibition is less pronounced in methylmercury-treated rats. Under these conditions PAD has little effect on the renal content, but increases the hepatic content of 75Se. It seems, therefore, that the methylation of selenite occurs mainly in the liver and in both control and methylmercury-treated animals, S-adenosylmethionine is the major methyl donor. It is possible that methylmercury does not affect directly the methylation enzyme system but, by competition for protein sulphydryl groups, increases the availability of the intermediary selenide anion.

Animals↗
PubMed1986

Steroid receptor activation: the glucocorticoid receptor as a model system.

The glucocorticoid receptor has been used as a model for steroid receptor activation. Because of recent evidence for the essentially nuclear location of the unoccupied receptors of 1,25-dihydroxycholecalciferol and 17 beta-estradiol, the significance of the activation mechanism converting unactivated receptor complexes to DNA-binding forms is unclear for some receptors. Up to now the weight of evidence favors a cytoplasmic location of the unactivated glucocorticoid receptor. In this article we describe studies on the nature of the activation mechanism and of regulatory factors.

Animals↗
PubMed1986

The toxicity and teratogenicity of mercuric mercury in the pregnant rat.

Mercuric mercury (Hg2+), when injected IV into the pregnant Wistar rat, is retained mainly in the maternal compartment and uptake by the conceptuses is small. Thus if the dose is based on total body weight, the maternal body burden, particularly in late gestation, is greater than the whole body burden in the non-pregnant animal. The LD50 of Hg2+ (mg/kg total body weight), however, remains essentially constant (1.0-1.2 mg Hg2+/kg) throughout pregnancy. It seems, therefore, that the rat becomes more resistant to Hg2+ with increasing gestational age. This increased resistance does not correlate with differences in (a) the uptake of Hg2+ by the kidneys, the target organs of toxicity, (b) the severity of the histopathologically detected renal damage and (c) the inhibition of glomerular filtration. Biochemical measurements, however, suggest that kidney function may become less susceptible to Hg2+ as pregnancy advances from conception to near term. During mid-gestation the minimum effective teratogenic dose of Hg2+ (0.79 mg/kg total body weight) is high in relation to the maternal LD50 and the incidence of foetal malformations, mainly brain defects (23% in all live foetuses), is low. In rats of different gestational ages uptake of Hg2+ by the embryo/foetus at this dose level decreases sharply between day 12 and day 13. The teratogenic effects in the foetus and both the structural and functional damage to the maternal kidneys, however, are essentially the same in animals that are dosed with Hg2+ either immediately before, or immediately after these gestational ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1986

Comparison of some biochemical effects of teratogenic doses of mercuric mercury and cadmium in the pregnant rat.

Mercuric mercury (Hg2+), like cadmium (Cd2+), interferes with the transport of certain essential metals to the conceptus in the pregnant Wistar rat and, at 48 h after the IV injection of a teratogenic dose (0.79 mg Hg2+/kg body weight) on day 12 of gestation, the foetal concentrations of Zn2+, Cu2+ and Fe3+, but not of Mg2+, are reduced significantly. Both Hg2+ and Cd2+, at teratogenic dose levels, inhibit the placental and foetal uptake of 65Zn2+ and 67Cu2+, but possibly by different mechanisms. In addition, the effects of Hg2+, at different times after dosing, on the uptake of these labelled tracers and of 59Fe3+, administered as 15-min pulses, do not parallel the changes in the placental and foetal concentrations and contents of the endogenous, stable metallic ions. The teratogenic dose of Hg2+ inhibits the placental and foetal uptake of L-[4,5-3H]-leucine, but not the incorporation of the labelled amino acid into foetal protein. In contrast, the corresponding dose of Cd2+ inhibits both leucine uptake and protein synthesis in the placenta and foetus. Similarly, Cd2+ inhibits the uptake of [2-14C]-thymidine and its incorporation into foetal DNA, whereas Hg2+ reduces the placental and foetal uptake, but has little or no effect on the utilization of the nucleoside. Since both Cd2+ and Hg2+ reduce the foetal uptake of 65Zn and the foetal concentration of Zn, but only Cd2+ interferes with DNA synthesis, it is unlikely that the inhibition of the metabolism of thymidine can be attributed to reduction in thymidine kinase activity in consequence of foetal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Neuronal differentiation of cloned human teratoma cells in response to retinoic acid in vitro.

We have analysed immunocytochemically the differentiation in vitro of clones of the human teratoma cell line Tera-2. The proliferating stem cells expressed Thy-1 and N-CAM/D2-CAM antigens. On treatment with 5 X 10(-5) M retinoic acid in either monolayer or aggregate cultures they began to express receptors for tetanus toxin and McAb A2B5. Three weeks after initiating retinoic acid treatment, the cultures contained a variety of cell morphologies, including about 3% of cells with a neuron-like morphology. These cells were reactive with tetanus toxin, McAb A2B5, and antibodies against Thy-1 and N-CAM/D2-CAM. They also expressed 55 000 and 210 000 Da neurofilament subunits.

Animals↗