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Biomedical subjects

J K Chesters

Publications and source records attributed to J K Chesters.

At least 19 recordsLinked to original sources
PubMed1992

Trace element-gene interactions.

For many of the genes encoding proteins involved in the transport, storage, and function of the trace elements, expression is regulated by the availability of the elements concerned. This control is exercised through a variety of mechanisms, including metal-activated transcription factors, modified usage of stop codons, and use of secondary structure within mRNA to regulate its translation and stability. Two widely represented groups of transcription factors, often classed as zinc-finger proteins, depend on constituent zinc ions for their activity. In addition, the sensitivity of growth and fetal development to the lack of zinc is hypothesized to relate to a requirement for the element during certain critical alterations in gene expression. The evidence for this and possible underlying mechanisms is examined.

Amino Acid Sequence↗
PubMed1991

Inhibition of myoblast differentiation by lack of zinc.

The impact of restricted zinc availability on myoblast differentiation was investigated. Lack of zinc prevented myoblast fusion and the increase in muscle-specific creatine kinase activity. The depression of activity of creatine kinase in the zinc-deficient cultures was accompanied by a similar decrease in the concentration of creatine kinase mRNA and was apparent even when fusion of the myoblasts was inhibited by cytochalasin B. Thus zinc appears to be necessary for the expression of creatine kinase during myoblast differentiation.

Animals↗
PubMed1991

Nature of the Zn2+ requirement for DNA synthesis by 3T3 cells.

Transit of 3T3 cells from quiescence to S phase requires an adequate supply of Zn2+ during the second half of the transition. The nature of this requirement has been investigated. Completion of the Zn2(+)-dependent process required ongoing mRNA and protein synthesis but could be accomplished in serum-free medium. Combination of low Zn2+ availability with inhibition of mRNA synthesis by 5,6-dichlororibofuranosylbenzimidazole or of protein synthesis by cycloheximide resulted in the cells almost completely reverting to a quiescent state. The results suggest that Zn2+ is required for the accumulation and maintenance of a protein involved in the progression of untransformed cells into S phase.

Animals↗
PubMed1990

A requirement for Zn2+ for the induction of thymidine kinase but not ornithine decarboxylase in 3T3 cells stimulated from quiescence.

In 3T3 cells stimulated from quiescence by serum, impaired thymidine incorporation caused by inadequate supply of Zn2+ was associated with both decreased thymidine kinase activity and a comparable decrease in its mRNA concentration. In contrast, the amount of mRNA for ribosomal protein S6 was not affected, nor was the earlier increase in the activity of ornithine decarboxylase.

Animals↗
PubMed1989

Specificity and timing of the Zn2+ requirement for DNA synthesis by 3T3 cells.

Addition of the chelator DTPA to synchronized cultures of 3T3 cells inhibited thymidine incorporation by up to 90% and only Zn2+ of the divalent cations tested was effective in reversing this effect. Fe2+ given alone had no effect on the inhibition by DTPA but when added to Zn2+ supplemented cultures increased thymidine incorporation from approximately 80-90 to over 100% of that in control cultures. Investigations indicated that the major requirement for Zn2+ was within the period from 8 h after stimulation of quiescent cells with serum until 3 h before the start of S phase. There was also an indication of a further requirement for Zn2+ at the G/S transition.

Animals↗
PubMed1988

Reduction of radiocaesium absorption by sheep consuming feed contaminated with fallout from Chernobyl.

Two compounds, a zeolite, clinoptilolite, and a ferrocyanide, potassium hexacyanocobalt (II) ferrate (II), were found to be the most effective adsorbers of caesium in vitro. When used in vivo they significantly reduced the absorption of caesium by sheep fed contaminated herbage. These compounds did not alter the rate of excretion of pre-absorbed caesium, which varied with the time from cessation of contamination.

Absorption↗
PubMed1987

Identification of thiomolybdates in digesta and plasma from sheep after administration of 99Mo-labelled compounds into the rumen.

1. At 16 h after the rapid injection of 99Mo-labelled compounds into the rumen of sheep maintained on dried grass (6.2 mg molybdenum/kg dry matter (DM), 4.3 g sulphur/kg DM), labelled thiomolybdates associated with the digesta solids or bound to plasma macromolecular species were displaced from their carriers in vitro and identified by Sephadex G25 chromatography. 2. After molybdate injection, the thiomolybdates displaced from rumen, duodenal and ileal solids were predominantly the trithio- and tetrathio- species. Dithiomolybdate was present to a relatively minor extent. Trace amounts of di- and trithiomolybdates were detected in the liquid phase of digesta from the duodenum. 3. Whether injected into the rumen as molybdate or tetrathiomolybdate, bound 99Mo appearing in plasma was present mainly as di- and trithio- species. The tetrathio- species appeared in trace amounts in plasma only after tetrathiomolybdate injection, despite its existence almost exclusively in this form in rumen digesta. 4. The present study provides direct evidence for thiomolybdate synthesis within the rumen and indicates that while the effects of thiomolybdates in inhibiting copper absorption are likely to be due to tri- and tetrathiomolybdates, post-absorptive effects on Cu metabolism are probably due to di- or trithiomolybdate.

Animals↗
PubMed1985

A new bioassay for assessment of copper availability and its application in a study of the effect of molybdenum on the distribution of available Cu in ruminant digesta.

Investigations were carried out on the feasibility of using an oral repletion technique in the rat to assess the bioavailability of copper in experimental sources providing no more than 250 micrograms Cu from any one source. Preliminary studies on the response in plasma Cu of partially Cu-depleted rats given repletion doses of 20-50 micrograms Cu as CuSO4/d on four consecutive days indicated that this index of Cu status was insufficiently sensitive to Cu dose. In contrast, the activity of cytochrome c oxidase (EC I.9.3.I) in the duodenal mucosa of partially Cu-depleted rats showed a measurable and uniform response to 10 micrograms Cu as CuSO4/d given on three consecutive days. Furthermore, when the rats were given 0, 2.5, 5.0 or 10.0 micrograms Cu/d, the increase in cytochrome c oxidase activity above that of the unsupplemented control group was linearly related to Cu dose. The mean response in cytochrome c oxidase activity in groups of eight rats was therefore used to assess the availability of Cu from experimental sources relative to that of Cu as CuSO4, only 240 micrograms Cu being required from each experimental material. The assay was used to study the effect of the Cu-antagonist molybdenum on the distribution of available Cu in digesta from sheep given dried grass either untreated (1.6 mg Mo/kg dry matter (DM)) or treated with ammonium molybdate (11.6 mg Mo/kg DM). The relative availability of Cu in untreated dried grass (75%) was substantially higher than in rumen (12%), duodenal (43%) or ileal (28%) digesta. In all cases, addition of Mo to the diet resulted in a substantial reduction in Cu availability. The effects of Mo on availability of Cu are discussed with special reference to the possible involvement of thiomolybdates in the Cu-Mo antagonism.

Animal Feed↗
PubMed1978

The assessment of zinc status of an animal from the uptake of 65Zn by the cells of whole blood in vitro.

1. 65Zn uptake by blood cells in vitro has been compared with plasma Zn concentration and plasma alkaline phosphatase (EC 3.1.3.1) activity as indicators of an animal's Zn status. 2. Dietary Zn deficiency, low food intake, reduced dietary protein content and endotoxin administration all reduced plasma Zn concentration in the rat. In each case there was a parallel reduction in plasma alkaline phosphatase activity and an increase in 65Zn uptake in vitro by cells of whole blood. 3. A similar relationship between the three measurements existed in sheep with lowered plasma Zn concentrations whether these were caused by dietary deficiency or by post-surgical stress. 4. 65Zn uptake by cells of whole blood did not differentiate dietary Zn deficiency from the other factors which reduce plasma Zn under 'field' conditions. 5. 65Zn uptake by the cells in whole blood in vitro was three to five times less rapid in blood of ruminant origin than in that from non-ruminants. This difference related to the erythrocytes rather than to the leukocytes or the plasma.

Alkaline Phosphatase↗
PubMed1978

Effect of age, weight and adequacy of zinc intake on the balance between alkaline ribonuclease and ribonuclease inhibitor in various tissues of the rat.

1. Deficiency of zinc inhibits growth and also increases the activity of alkaline ribonuclease in certain tissues of the rat (Prasad & Oberleas, 1973). Zn could influence ribonuclease activity by direct effects on the enzyme or its natural inhibitor, or non-specifically as occurs when growth rate is affected by various other factors. These possibilities were studied. 2. Alkaline ribonuclease was shown to be inhibited by Zn in vitro, but the concentrations of Zn required were so high that the enzyme was probably not directly affected by changes in tissue Zn concentration caused by dietary deficiency. 3. At lower concentrations, Zn added in vitro increased the activity of alkaline ribonuclease in tissue homogenates probably by inactivating the inhibitor of the enzyme. 4. Age, weight and particularly food restriction caused tissue-specific alterations of ribonuclease and ribonuclease inhibitor concentrations in liver, kidney, oesophagus, testis and thymus. 5. The ribonuclease activities in liver, kidney and testis of Zn-deficient rats were unaltered in comparison with those of pair-fed rats. In thymus, which decreased in weight in the Zn-deficient animals, there was a concomitant increase in ribonuclease activity, but in oesophagus, the deficiency reduced the activity of ribonuclease. 6. The effects of Zn deficiency upon alkaline ribonuclease and its inhibitor are probably secondary consequences of reductions in food intake or growth.

Age Factors↗
PubMed1975

Comparison of the effects of zinc deprivation and actinomycin D on ribonucleic acid synthesis by stimulated lymphocytes.

1. EDTA inhibited incorporation of [3H]uridine into RNA of lymphocytes, but did not decrease uptake into the cold-acid-soluble fraction of the cells. The inhibition by EDTA was largely reversible by simultaneous addition of Zn2+. 2. Low concentrations pf actinomycin D (3 ng/ml) added at the time of stimulation of the cells inhibited [3H]uridine incorporation into RNA, but concentrations of 50-100 ng/ml were required to produce the same degree of inhibition if addition of actinomycin D was delayed until just before the incorporation was measured. This difference in sensitivity did not reg within the cells. 3. When added immediately before phytohaemagglutinin, actinomycin D (3 ng/ml) and EDTA produced similar time-courses of inhibition of uridine incorporation. 4. Uridine incorporation at 32h was inhibited when actinomycin D (3 ng/ml) or EDTA was added just before stimulation of the cells, but was only slightly affected when they were added at 32h. At intermediate times the incorporation of uridine remained sensitive to addition of EDTA for longer than it was sensitive to actinomycin D. 5. Polyacrylamide-gel separation of RNA synthesized in EDTA-treated cultures in the presence or absence of added Zn2+ showed that lower availability of Zn2+ resulted in a decreased rate of transfer of radioactivity from 32S to 28S rRNA and decreased survival of 28S rRNA relative to 18S rRNA. 6. Close similarities have been shown to exist between the effects of EDTA and low concentrations of actinomycin D. Not all the effects of EDTA could be explained by postulating that Zn2+ was a constituent of RNA polymerase I, nor were the effects of actinomycin D readily explained by previously suggested mechanisms of action of this antibiotic.

Animals↗
PubMed1972

The role of zinc ions in the transformation of lymphocytes by phytohaemagglutinin.

1. Incorporation of [(3)H]thymidine into DNA was inhibited by EDTA and diethylenetriamine-NNN'N''N''-penta-acetate but not by nitrilotriacetate even when Ca(2+) was present at more than twice the concentration of the chelators. 2. The inhibition caused by EDTA was most effectively reversed by Zn(2+) but also to a lesser extent by Cd(2+). Very little if any activation of the EDTA-inhibited system was obtained with Co(2+), Cu(2+), Fe(3+), Mn(2+) or Ni(2+) added alone. 3. Fe(3+) added to the Zn(2+)-activated lymphocytes in the presence of EDTA markedly increased thymidine incorporation. Addition of Cd(2+) prevented the inhibition of incorporation which occurred at high Zn(2+) concentrations. 4. If EDTA was added more than 15h after phytohaemagglutinin, the inhibition of incorporation was less than that obtained by its addition at zero time. If Zn(2+) was added later than 12h after EDTA and phytohaemagglutinin, the inhibition of incorporation by EDTA was not fully reversed. A study of the time-course of the effects of delayed additions of EDTA and Zn(2+) suggested that, on average, the cells required Zn(2+) between 20 and 30h after phytohaemagglutinin addition to allow the full rate of thymidine incorporation at 37h. 5. The increase in the rate of protein synthesis caused by phytohaemagglutinin was not inhibited by EDTA until about 8h. The further increase after this was totally inhibited by EDTA but this inhibition was fully reversible with Zn(2+). The rate of protein synthesis in EDTA-inhibited cultures at 40h was the same as that at 10h. 6. There was a close similarity between the effects of EDTA on lymphocyte stimulation and those reported by Kay et al. (1969) with low doses of actinomycin D.

Animals↗