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S J Duncan

Publications and source records attributed to S J Duncan.

13 recordsLinked to original sources
PubMed2001

Isolation and structure elucidation of Chlorofusin, a novel p53-MDM2 antagonist from a Fusarium sp.

Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction of p53 can be caused by increased levels of the protein MDM2, small molecules which antagonize the interaction between these two proteins have potential in cancer therapy. The discovery and structure determination of a fungal metabolite, chlorofusin, which antagonizes the p53/MDM2 interaction are reported.

Antineoplastic Agents↗
PubMed1986

The role of condensed tannins in the nutritional value of Lotus pedunculatus for sheep. 4. Sites of carbohydrate and protein digestion as influenced by dietary reactive tannin concentration.

1. Vegetative secondary growth Lotus pedunculatus was cut daily, and fed fresh at hourly intervals (600 g dry matter (DM)/d) to three groups each of three sheep fitted with permanent cannulas into the rumen and duodenum. Lotus fed to two of the groups was sprayed with low and high rates of polyethylene glycol (PEG; molecular weight 3350), which specifically binds the condensed tannins (CT). Nutrient intake and faecal excretion were measured directly, duodenal flows estimated from continuous intraruminal infusion of inert ruthenium phenanthroline (Ru-P) and CrEDTA markers, and rumen pool sizes measured at slaughter. 2. Dietary concentrations of total reactive CT (i.e. that not bound to PEG) were 95, 45 and 14 g/kg DM, whilst the corresponding values for free CT were 15, 5 and 2 g/kg DM. 3. Increasing dietary reactive CT concentration linearly increased duodenal flows of non-ammonia nitrogen, but linearly decreased the apparent digestibility of energy and organic matter, and rumen digestion of hemicellulose but not of cellulose. Rumen digestion as a proportion of total digestion was increased by the higher PEG rate for organic matter, energy, pectin and lignin. 4. High dietary CT concentration was associated with increased N retention. Rumen ammonia concentration and pool size showed only a slight decline on this diet, indicating that there must have been increased recycling of N into the rumen. 5. Increasing dietary reactive CT concentration had no effect on the rate at which carbohydrate constituents were degraded in the rumen per unit time (FDR), but increased the rate at which their undegraded residues (FOR) left the rumen per unit time. The latter appeared to be the principal mechanism by which rumen digestion as a proportion of total digestion was reduced at high dietary CT concentrations. From a comparison of FDR and FOR of carbohydrate components in lotus and Brassica oleracea diets, it was concluded that hemicellulose digestion was rate-limiting for rumen cell-wall digestion, probably due to bonding with lignin. However, the considerable post-rumen digestion of hemicellulose was not associated with post-rumen lignin digestion. 6. It was concluded that a desired concentration of CT in Lotus sp. should represent a balance between the positive effect of CT in improving the efficiency of N digestion and their negative effect in depressing rumen carbohydrate digestion. A recommended concentration is 30-40 g/kg DM.

Animals↗
PubMed1984

The role of condensed tannins in the nutritional value of Lotus pedunculatus for sheep. 1. Voluntary intake.

Voluntary intake was determined with vegetative Lotus pedunculatus cut and fed fresh to growing sheep of 42-46 kg live weight. Effects attributable to condensed tannins were assessed by growing the plant under high and low levels of soil fertility, inducing low and high concentrations of tannin (Expt 1), or by binding the tannins through spraying the herbage with polyethylene glycol (molecular weight 3350, PEG; Expt 2). Primary-growth lotus was used in Expt 1 and secondary-growth lotus in Expt 2. Concentrations of total and free condensed tannin were determined in fresh lotus, free tanning being defined as that not bound by mascerates of the plant. In Expt 1 the herbages fed contained respectively 46 and 106 g total condensed tannin/kg dry matter (DM) and 3 and 14 g free condensed tannin/kg DM. Mean metabolizable energy (ME) intakes were 0.89 and 0.77 MJ/kg live weight0 .75 per d (P less than 0.05) respectively. The lotus used in Expt 2 contained 63 and 5 g total reactive condensed tannin and free condensed tannin/kg DM respectively. After spraying with PEG at 2.4 g/g total condensed tannin, these values were reduced to 7 and 0.5 g/kg DM respectively. PEG addition increased apparent digestibility (proportion of each nutrient ingested) of cellulose, hemicellulose and nitrogen by 0.05, 0.08 and 0.26, and increased ME intake from 0.48 to 0.69 MJ/kg live weight0 .75 per d. It was concluded that high concentrations of condensed tannins depressed ME intake, due to depressions in both the voluntary intake and digestion of organic matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1983

The effects of razoxane (ICRF 159) on the production of collagenase and inhibitor (TIMP) by stimulated rabbit articular chondrocytes.

Monolayer cultures of rabbit chondrocytes were stimulated to produce collagenase with conditioned medium from human peripheral blood mononuclear cells (MCM), and the ability of Razoxane to modulate the production of collagenase and specific tissue inhibitor of metalloproteinases (TIMP) was studied. Collagenase production was inhibited and TIMP increased by Razoxane, in a dose-dependent manner, when cells were treated daily for 3 days. Over this period the effect of Razoxane was progressive; 50 micrograms/ml or less had no effect at day 1 but 50 micrograms/ml was effective by day 3. The effectiveness of Razoxane was inversely related to the degree of MCM stimulation and the confluency of the culture. On removal of the drug, chondrocytes stimulated with MCM recovered their ability to produce collagenase, and TIMP production returned to near normal. The results suggest that the ability of Razoxane to reduce collagenase and increase TIMP production may correlate with its effectiveness in treating psoriatic arthritis.

Animals↗
PubMed1983

Copper metabolism in growing sheep given kale (Brassica oleracea) and ryegrass (Lolium perenne)-clover (Trifolium repens) fresh forage diets.

Kale (Brassica oleracea) and ryegrass (Lolium perenne)-clover (Trifolium repens) pasture grown under similar soil conditions were grazed in the vegetative state by growing lambs of 23.6 kg initial live weight for 24 weeks. Forty-eight lambs grazed each forage. The kale and pasture contained respectively 4 and 14 mg copper/kg dry matter (DM), 7.2 and 3.1 g total sulphur/kg DM and 0.4 and 1.1 mg molybdenum/kg DM. Subcutaneous injections of Cu (12 mg) were given to half the animals grazing each forage during weeks 1, 6, 12 and 18. All ninety-six animals were slaughtered at the end of the experiment and an additional group of twelve animals was slaughtered when the experiment commenced. Liver Cu was determined on all slaughtered animals and heart muscle cytochrome oxidase (EC 1.9.3.1) activity on those slaughtered at week 24. Blood samples removed at 6-week intervals were assayed for activity of superoxide dismutase (EC 1.15.1.1; SOD) and serum Cu concentration determined. Wool growth, live-weight gain and cytochrome oxidase activity of biopsied hind-limb muscle were also measured at 6-week intervals. Control animals grazing pasture showed an accumulation of total liver Cu during the experiment. Animals grazing this diet and given Cu injections showed an additional accumulation of liver Cu equivalent to the supplementary Cu administered, but Cu supplementation did not affect the activity of any of the Cu-containing enzymes measured and did not affect live-weight gain or wool growth. Control animals grazing kale showed a depletion of total liver Cu and reductions in serum Cu concentrations during weeks 18 and 24.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1983

Antibody response to pneumococcal vaccination in children younger than five years of age.

Sera were analyzed by radioimmunoassay for type-specific pneumococcal antibody in 249 children aged six to 54 months, who were participating in a controlled trial of a 14-valent pneumococcal vaccine. Levels of serum antibody to all serotypes increased after immunization in all age groups tested. For all serotypes, the antibody response increased progressively with age whether response was viewed as antibody doubling, relative increase in geometric mean, or final antibody level. Responses were poor up to the age of five years for the important pediatric serotypes 6A, 14, 19F, and 23F. Seventeen children under the age of two years at the time of primary immunization received booster doses of vaccine six months later. There was no significant increase in antibody to any serotype, and the geometric mean antibody levels fell for most types. Immune response to the pediatric serotypes was poor until the age of 4.5 years.

Aging↗
PubMed1981

The effect of non-phorbol promoters as compared with phorbol myristate acetate on sister chromatid exchange induction in cultured Chinese hamster cells.

The effect of 5 unrelated chemicals with different promoting potencies on sister chromatid exchange (SCE) induction in V79 cells was investigated. Two powerful promoters--12-O-tetradecanoylphorbol-13-acetate (TPA) and anthralin; a moderate promoter--iodoacetic acid (IAA); two weak promoters--ethyl phenylpropiolate (EPP) and cantharidin--all induced similar and low numbers of SCE. These results do not support the hypothesis that enhanced mitotic recombination is responsible for tumour promotion.

Animals↗
PubMed1979

Lack of oestradiol-DNA binding in mouse embryo cell cultures or following rat-liver microsomal metabolism.

Oestradiol-17beta was compared to benzo[a]pyrene (BP) for its ability to bind to the DNA of mouse embryo cells in culture or to DNA added to a rat liver microsomal incubation mixture. No significant binding was found in embryo cells (at least 100-fold less than for BP). Microsomal incubation resulted in apparent oestradiol binding to a reisolated DNA-containing complex, but most of this was lost when the DNA was freed of RNA and protein.

Animals↗
PubMed1978

Infection of mouse liver by human adenovirus type 5.

CBA mice, inoculated intravenously with large doses of adenovirus type 5, showed raised levels of serum aspartate aminotransferase (SAAT; EC 2.6.I.I) and died within a few days from histologically demonstrable hepatic necrosis. After inoculation of I LD50, virus was rapidly taken up by the tissues where infectivity then declined greatly. Organ titres then increased about 100-fold by 48 h p.i. but, in the liver, which showed intranuclear inclusion bodies, and by electron microscopy, scattered intranuclear and intracytoplasmic adenovirions, the increase was 10000- to 100000-fold. P antigen was detected by single radial diffusion in liver extracts, and by immunofluorescence in 80% of liver cells at 36 h p.i. Hexon, penton base and fibre antigens appeared later and in fewer cells. The maximum amount of hexon, of demonstrable type 5 specificity, was shown by radioimmunoassay to be equivalent to up to 5 x 1011 whole adenovirions/g liver. It is concluded that human adenovirus type 5 undergoes an abortive but lytic infection in most liver cells but that replication may proceed to completion in a few.

Adenoviridae Infections↗
PubMedDate not supplied

Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart.

G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors, including alpha(1B)-adrenergic receptors (ARs), resulting in desensitization. In vivo analysis of GRK substrate selectivity has been limited. Therefore, we generated hybrid transgenic mice with myocardium-targeted overexpression of 1 of 3 GRKs expressed in the heart (GRK2 [commonly known as the beta-AR kinase 1], GRK3, or GRK5) with concomitant cardiac expression of a constitutively activated mutant (CAM) or wild-type alpha(1B)AR. Transgenic mice with cardiac CAMalpha(1B)AR overexpression had enhanced myocardial alpha(1)AR signaling and elevated heart-to-body weight ratios with ventricular atrial natriuretic factor expression denoting myocardial hypertrophy. Transgenic mouse hearts overexpressing only GRK2, GRK3, or GRK5 had no hypertrophy. In hybrid transgenic mice, enhanced in vivo signaling through CAMalpha(1B)ARs, as measured by myocardial diacylglycerol content, was attenuated by concomitant overexpression of GRK3 but not GRK2 or GRK5. CAMalpha(1B)AR-induced hypertrophy and ventricular atrial natriuretic factor expression were significantly attenuated with either concurrent GRK3 or GRK5 overexpression. Similar GRK selectivity was seen in hybrid transgenic mice with wild-type alpha(1B)AR overexpression concurrently with a GRK. GRK2 overexpression was without effect on any in vivo CAM or wild-type alpha(1B)AR cardiac phenotype, which is in contrast to previously reported in vitro findings. Furthermore, endogenous myocardial alpha(1)AR mitogen-activated protein kinase signaling in single-GRK transgenic mice also exhibited selectivity, as GRK3 and GRK5 desensitized in vivo alpha(1)AR mitogen-activated protein kinase responses that were unaffected by GRK2 overexpression. Thus, these results demonstrate that GRKs differentially interact with alpha(1B)ARs in vivo such that GRK3 desensitizes all alpha(1B)AR signaling, whereas GRK5 has partial effects and, most interestingly, GRK2 has no effect on in vivo alpha(1B)AR signaling in the heart.

Animals↗