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Biomedical subjects

B W Young

Publications and source records attributed to B W Young.

36 records · Page 2Linked to original sources

Investigation of the structure of metallothioneins by proton nuclear magnetic resonance spectroscopy.

The proton nuclear magnetic resonance spectra of metallothioneins from horse, human, and sheep livers were investigated. The spectra of the metallothioneins from the three species are similar as are the two isoproteins from any one species. The spectra indicate that metallothioneins possess a well-defined tertiary structure. Zinc(II) and calcium(II) ions induce similar but not identical tertiary structures. Confirmatory evidence was obtained for the involvement of cysteine residues in metal binding, but no evidence was obtained for the involvement of any other amino acid residue in metal binding. The apoprotein thionein was found to exist essentially in a random-coil conformation with perhaps some residual segmental structure.

Animals↗

Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat.

A study has been made of the mechanism of the mutual antagonism between copper and zinc in rats. Dietary zinc concentrations of up to 450 mg/kg had no effect on intestinal 64Cu absorption but 900 mg/kg caused a 40% reduction. This was associated with an increase in the mucosal uptake of 64Cu in the small intestine. This occurred mainly in the form of metallothionein and it appeared that copper displaced zinc from the protein after its synthesis had been induced by zinc. Ths intestinal absorption of 65Zn was decreased by 20% when the dietary copper intake was increased from 3 to 24 mg/kg. Further increases in copper intake to 300 mg/kg did not cause any additional decrease in 65Zn absorption or any change in the association of intestinal 65Zn with metallothionein. Concentrations of this protein in the intestinal mucosa were not influenced by dietary copper intake.

Animals↗

Effect of zinc status of rats on the synthesis and degradation of copper-induced metallothioneins.

Injection of Zn2+-adequate and Zn2+-deficient rats with Cu2+ stimulated the incorporation of l-[35S]cysteine into a low-molecular-weight Cu2+-binding protein in both liver and kidney. No significant incorporation of l-[4,5-3H]leucine into this protein occurred, confirming the previous claim that it was metallothionein and not some other leucine-rich protein. The half-life of the protein was found to be 16.9 +/- 1.0 (S.E.)h in the liver of Zn2+-adequate rats but only 12.3 +/- 0.5h in Zn2+-deficient animals. The degradation rate of the metallothionein was similar to the rate of disappearance of Cu2+ and Zn2+ from the protein, indicating that the release of mental from the protein and its catabolism occurred simultaneously. There was no significant difference in the half-lives of the hepatic or renal copper-thioneins in Zn2+-adequate rats.

Animals↗

Metabolism of 35S-labelled copper-, zinc-and cadmium-thionein in the rat.

A comparative study has been made of the metabolism in the rat of intravenously-administered hepatic copper-, zinc- and cadmium-thioneins. In all cases the 35S-labelled protein was rapidly removed from the circulation. About 20% of the 35S was present in the kidneys after 30 min byt only small amounts of 35S were found in the liver, intestinal mucosa or pancreas. In the case of copper-thionein, 30% of the injected 35S was recovered in the urine within 2 h, mainly as intact copper-thionein. The 35S which appeared in the kidneys was also present initially as metallothionein but this was degraded very rapidly, especially when zinc-thionein was give. Both copper and cadmium from the injected proteins accumulated in the kidneys as metallothionein, but there was no increase in renal zinc concentrations in the rats dosed with zinc-thionein. These findings are discussed in relation to the development of renal damage in chronic cadmium and copper toxicity.

Animals↗

Effects of dietary molybdenum and sulphur on the distribution of copper in plasma and kidneys of sheep.

1. A 30-week study has been made in growing ewe lambs of the effects of dietary supplementation with molybdenum, or Mo plus inorganic sulphate on the distribution of copper in their blood plasma and kidneys. 2. The addition of 25 mg Mo and 5 g SO42-/kg diet increased Cu concentrations in plasma and kidney and decreased those in liver. Plasma caeruloplasmin activities (ferroxidase; EC 1.16.3.1) were unaffected. 3. Subcellular fractionation of the kidney cortex and gel filtration of the plasma and kidney cortex cytosol showed that the increased Cu content of these tissues was associated with abnormalities in the distribution of Cu. It appeared that both Cu and Mo were associated with the same proteins. 4. Dietary supplementation with Mo alone (25 mg/kg) had no effect on plasma or kidney Cu concentrations, suggesting that S metabolism is involved in the formation of the abnormal Cu-binding proteins in plasma and kidney. 5. The results are discussed in relation to the induction of Mo-induced Cu-deficiency states and the possible involvement of thiomolybdates.

Animals↗

Copper thionein in the kidneys of copper-poisoned sheep.

A study has been made of the distribution of copper in the kidneys of copper-poisoned sheep, containing up to 240 microgram copper/g fresh cortex. About 64% of the copper in the cortex was present in the cytosol and 75% of this occurred in a form with molecular weight of approx. 12 000. This was partially purified by gel filtration on Sephadex G-75 and Bio-Gel P.10 and ion exchange chromatography on DEAE Sephadex A-25 to give three sub-fractions, which also contained zinc. The amino acid composition, copper content and chromatographic behaviour of these proteins indicated that they were copper-thioneins. No significant amounts of the proteins were detected in the plasma or erythrocytes of the copper-poisoned sheep when they were undergoing the haemolytic crisis typical of this syndrome. It is concluded that metallothionein constitutes the major copper-binding protein in the kidneys of copper-poisoned sheep. However the rapid accumulation of the protein in the kidney, and the development of kidney damage, are unlikely to have arisen from the release of the intact copper-protein from the liver and its transport via the blood to the kidneys.

Amino Acids↗

Distribution of copper and zinc in the liver of the developing sheep foetus.

1. A study has been made of the copper- and zinc-binding proteins in the livers from sheep foetuses of 80-142 d gestational age. 2. Metallothionein was found to constitute the major Zn-binding component in the cytosol at all times and to be identical to Zn-thionein from adult sheep liver. 3. Zn also occurred in two fractions, not normally found in sheep liver, with approximate molecular weights of 28000 and 47000. The relative proportions of these were age-dependent. 4. Between 15 and 35% of the hepatic Cu, corresponding to most of the Cu in the cytosol, also occurred in the metallothionein-containing fraction.

Amino Acids↗

Isolation of (copper, zinc-) thioneins from pig liver.

The copper-binding proteins with mol. wt. of approx. 12000 in the cytosol of pig liver have been identified as copper-thioneins. They contain variable amounts of zinc, with approx. 10% total metal in the protein. The molar cysteine/metal ratio is approx. 2:1.

Amino Acids↗

Protective effect of zinc supplementation against copper toxicosis in sheep.

1. A study has been made of the effects of dietary zinc supplementation on the development of copper toxicosis in three groups each of eight 12-week-old lambs. 2. None of the lambs receiving 420 mg Zn/kg diet developed Cu toxicosis in the 24-week experimental period, compared with three in the control group receiving 43 mg Zn/kg and possibly one in the group receiving 220 mg Zn/kg. 3. Liver Cu concentrations were reduced by up to 40% in the Zn-supplemented animals, with concomitant reductions, especially in the early stages of the experiment, in the extent of liver damage, as assessed by measurement of plasma aspartate aminotransferase (EC 2.6.1.1) and arginase (EC 3.5.3.1) activities. 4. Plasma and liver Zn concentrations were increased only slightly in the lambs receiving the Zn-supplemented diets, and the only indication of possible toxic effects of the Zn supplements was the development of a slight anaemia in those animals receiving 420 mg Zn/kg diet. 5. The results suggest that the incidence of Cu toxicosis in sheep may be controlled by increasing their dietary Zn intake.

Animals↗

Clinical experience with 99mTc-DMSA (dimercaptosuccinic acid), a new renal-imaging agent.

Results are reported from the clinical evaluation of a new radiopharmaceutical for renal imaging, 99mTc-DMSA (dimercaptosuccinic acid). Sixty-five patients were studied and six of these patients' scintiphotos are illustrated. The physical characteristics of 99mTc and the mercurial-like kinetics of the chelate produced high-resolution scintiphotos of the renal parenchyma in patients of all ages and with a variety of disease entities. The commercial availability of the material in kit form permits its usage in all nuclear medicine facilities.

Abscess↗