Search PubMed⌕ Search

Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 757 records · Page 42Linked to original sources

Protein phosphorylation in respiring slices of guinea-pig cerebral cortex. Evidence for a role for noradrenaline and adenosine 3':5'-cyclic monophosphate in the increased phosphorylation observed on application of electrical pulses.

1. Exposure of slices of cerebral cortex from guinea pigs to electrical pulses for 10s or to noradrenaline, 5-hydroxytryptamine or histamine increases the rate of phosphorylation of unidentified proteins in the tissue; the increases in protein phosphorylation due to electrical pulses and noradrenaline were non-additive, whereas the increases due to pulses and 5-hydroxytryptamine or histamine were additive. 2. The stimulating effects of electrical pulses and noradrenaline on protein phosphorylation were antagonized by the beta-adrenergic blocking agents L-propranolol, dichloroisoprenaline, practolol and ICI 66082, but not by the alpha-adrenergic blocking agents, phentolamine and phenoxybenzamine. 3. The increase in protein phosphorylation associated with electrical pulses was antagonized by 10 mum-trifluoperazine and 0.5 mum-prostaglandin E1. 4. It is postulated that under the experimental conditions used the action of electrical pulses on protein phosphorylation is mediated by noradrenaline acting through a beta-adrenergic receptor mechanism probably involving adenylate cyclase.

Adrenergic alpha-Antagonists↗

Potential antitumor agents: a cytotoxic cardenolide from Coronilla varia L.

An alcoholic extract of the seeds of Coronilla varia L. showed inhibitory activity against KB cells in culture and was fractionated through a series of partitions, column chromatography, and preparative layer chromatography to yield hyrcanoside, daphnoretin, scopoletin, and umbelliferone. Hyrcanoside was also tested in the PS mouse leukemia assay and showed borderline activity.

Animals↗

Recent life changes and outcome of prolonged competitive stress.

To test the predictive utility of subjects' recent life changes with regard to outcome of prolonged competitive stress, the authors studied racers (N = 25) in a long distance Alaskan sled race, the Iditarod. Rank order correlations between subjects' 1-year life change units (LCU) total and adjusted place of finish proved significant by both Kendall's and Spearman's Test. Thus, lowe LCU scores correlated with better performance and higher scores with poorer performance. Differences between subgroupings of the racers are considered. The work suggests that the usefulness of recent life changes assessment may be extended beyong physical illness, particularly in the study of response and adaptation to prolonged stress.

Age Factors↗

Pilo-sebaceous duct physiology. III. Observations on the number and size of pilo-sebaceous ducts in acne vulgaris.

We have used surface microscopy to measure the pil-sebaceous duct orifices at different sites in 150 subjects. Our data have shown that there are more pilo-sebaceous units on the face compared to the back and that these exists are smaller on the face. Despite the small exit the sebum excretion rate per gland on the forehead was not significantly different from that on the back. Thus the number of pilo-sebaceous duct units and the pilo-sebaceous canal exit size are possible factors in the localization of acne.

Acne Vulgaris↗

Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. II. Effects on macromolecular synthesis in cell culture and evidence for alkylating activity.

2,5-Piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride (NSC-135758) inhibited DNA synthesis but not RNA and protein synthesis in Adenocarcinoma 755 cells in culture. The expression of such inhibition was delayed in time; it was necessary to expose tumor cells to NSC-135758 for 10-12 hours before measuring the macromolecular synthesis in order to demonstrate selective inhibition of DNA synthesis. Inhibition of DNA synthesis was demonstrated to be irreversible in human epidermoid carcinoma cells in culture. Exposure of cells in suspension culture to NSC-135758 or to melphalan for 1-4 hours, and then incubation of cells in the absence of an inhibitor for 20 hours, resulted in preferential inhibition of DNA synthesis; inhibition of RNA synthesis was observed under these conditions but was less pronounced. Chemical evidence for alkylating activity of NSC-135758 and of the bis-aziridine derived from it (NSC-201424) was obtained by demonstrating their reaction with 4-(p-nitrobenzyl)pyridine. NSC-135758 was more potent as a cytotoxic agent than was its derivative, a result which suggests that NSC-135758 is the active alkylating agent. Reaction of NSC-135758 with diethylamine was examined; the product obtained upon alkylation of diethylamine by NSC-135758 was identified from its proton magnetic resonance spectrum and by field desorption mass spectral analysis. These results support the view that NSC-135758 acts as an alkylating agent in inhibiting DNA synthesis and cell proliferation of tumor cells in culture.

Adenocarcinoma↗

The mechanism of action of 3-deazauridine in tumor cells sensitive and resistant to arabinosylcytosine.

Deazauridine inhibited growth of tumor cells in culture and in culture and in vivo; this agent was significantly more effective against L1210/AraC than against the parent sensitive line. Inhibition of growth of tumor cells in culture was prevented by uridine and cytidine and was partially alleviated by deoxycytidine, but not by deoxyuridine or thymidine. DeazaUR inhibited nucleic acid synthesis but not protein synthesis in tumor cells in culture; deoxycytidine alleviated inhibition of nucleic acid synthesis. The labeling of pyrimidine ribonucleotides by 6-14C-orotic acid was inhbited by deazaUR. DeazaUR treatment of tumor cells in culture resulted in increased uptake of cytidine-3H into RNA, whereas uridine-3H uptake into RNA was inhibited. Labelling of DNA by uridine-3H/ and cytidine-H was inhibited by deazaUR. Pools of CMP, CDP, and CTP decreased markedly during deazaUR treatment of L1210 cells in culture and in vivo. These observations in growing cells pointed to deazaUR inhibition of the synthesis of cytidylic acid. Deazauridine 5'-triphosphate was found to be an inhibitor of the synthesis of CTP from UTP catalyzed by enzyme preparations from L1210 cells. This observation is in agreement with those of McPartland et al.19 that deazaUTP inhibited CTP synthetase purified from calf liver. Deazauridine treatment of L1210 cells in culture stimulated the uptake of deoxycytidine-3H into DNA while inhibiting the uptake of 3H-labeled deoxyuridine, thymidine, deoxyadenosine, and deoxyguanosine. Intracellular pools of dCTP were decreased by deazauridine treatment in L1210 cells in culture and in vivo. Deazauridine 5'-diphosphate inhibited the enzymatic reduction of pyrimidine ribonucleoside 5'-diphosphates to the corresponding deoxyribonucleotides. These results are consistent with the view that deazauridine, after its uptake and intracellular phosphorylation, strongly inhibits the formation of CTP. This is considered to be the primary metabolic effect of the analog. A secondary effect appears to be an inhibition of dCTP formation.

3-Deazauridine↗

Induction of fescue foot syndrome in cattle by fractionated extracts of toxic fescue hay.

Tall fescue (Festuca arundinacea Shreb) hay from a source known to cause "fescue foot" in grazing cattle was extracted with 80% ethanol. The ethanolic extract was further refined and fractionated into cation,nion, and neutral f fractions by ion-exchange chromatography. The cation fraction was partitioned with alkaline-chloroform to give chloroform-extractable cation and residual cation fractions. All fractions plus the crude ethanolic extract were assayed for toxic activity by intraperitoneal injection into 12 calves (weighting 152.4 to 241.3 kg each) over a 14-day period. Clinical signs of fescue foot were observed on the 5th day in calves given the anion and crude ethanolic extracts. Lameness, swelling, and reddening of the rear coronary bands, discoloration of the tip of the tail, and other signs of fescue foot were seen. Microscopically, coronary bands and tail tips of affected calves had blood vessels with thick walls and small lumens.

Animals↗

An explanation fro chloracne -- an industrial hazard.

Patients with chloracne were investigated and the results compared with data matched for age and site from patients with acne vulgaris. The ultrastructural appearances of pilo-sebaceous ducts in both groups were similar. The industrial group had significantly fewer C. acnes than the patients with ordinary acne. They also showed a significant increase in the surface lipid percentage composition of squalene, wax ester and cholesterol and this was associated with a significant decrease in the triglyceride free fatty acids and total triglyceride pool. We suggest that the acnegenic agent has produced its effect by modifying the metabolism of the pilo-sebaceous fluid.

Acne Vulgaris↗