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Biomedical subjects

T Wilson

Publications and source records attributed to T Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1986

The effect of progesterone on the release of arachidonic acid from human endometrial cells stimulated by histamine.

Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity.

Arachidonic Acid↗
PubMed1986

Comparative pathological aspects of chronic olivine and silica inhalation in mice.

A comparative study was done in mice on the effects of silica and olivine inhalation. The exposure periods in the dust chambers were for periods of 150, 300, and 570 days, with the longest time period covering a large portion of the predicted life span of the Balb/c mouse. Detailed necropsies including histology were done at the end of the exposures and at 30 and 150 days following removal of animals from the 150- and 300-day dust exposures. The results indicate that silica causes considerably more tissue damage in lungs and mediastinal lymph nodes, leading to granulomas.

Animals↗
PubMed1986

3,4-Dihydro-2-phenyl-2H-pyrano[2,3-b]pyridines with potent antirhinovirus activity.

A general synthesis to the title compounds 1, substituted in the 6-position and on the phenyl ring, is outlined. Eighteen analogues were compared with respect to in vitro activity against rhinovirus types 1A, 9, and 64. Compounds 1c and 1h, the 6-bromo- and 6-(methylsulfonyl)-3',4'-dichlorophenyl analogues, afforded median MIC50 values against 23 rhinovirus serotypes of 0.05 and 0.13 micrograms/mL, respectively. Mice dosed orally with 200 mg/kg of 1c or 1h exhibited serum levels well in excess of each compound's MIC50, indicating that some analogues have the potential to be orally effective drugs.

Animals↗
PubMed1986

Absorption of individual fatty acids from long chain or medium chain triglycerides in very small infants.

Using stool samples previously obtained for a nutritional balance study of very small infants, the intake, excretion, and percent absorption (%A) of individual fatty acids were quantitated by gas-liquid chromatography in two groups of patients; one receiving a formula providing fat as long chain triglycerides (LCT), the other providing 40% fat as medium chain triglyceride (MCT). The total fat intake for each group was 7.22 g/kg/day (MCT group), 6.02 g/kg/day (LCT group) and the absorption was 6.79 g/kg/day (MCT group) and 5.41 g/kg/day (LCT group). The %A of individual acids was comparable in both groups being greater than 99% for MCT and being lowest (62%) for C18:0 FA. As a consequence, infants in the MCT-fed group had a better total %A of fat, 95.2 vs 89.9% and absorbed more fat than the LCT group.

Chromatography, Gas↗
PubMed1985

Partial purification and characterisation of two compounds from amniotic fluid which inhibit phospholipase activity in human endometrial cells.

Two inhibitors of PGF synthesis in human endometrial cells were found in amniotic fluid from term non-labouring patients. Both inhibitors at 10(-9)M reduced the amount of arachidonic acid released from the cells but had no effect on PGF synthesis stimulated by arachidonic acid. The molecular weights were 150-165,000 and 70-80,000 daltons as estimated from gel filtration in two systems. Both compounds precipitated with ammonium sulfate, appeared thermostable and lost activity with trypsin digestion. Both inhibited phospholipase activity and had identical retention times with HPLC. We conclude that the compounds are novel endogenous proteins which inhibit endometrial cell phospholipase.

Amniotic Fluid↗
PubMed1985

Indirect [3H]methyl exchange as a general method for labeling methionine residues: application to calcitonin.

Native porcine calcitonin from Armour is known to contain two components. It is shown that these can be separated by cation-exchange chromatography in 8 M urea. The technique of [3H]methyl exchange on the methionine residue was used to prepare each of these in a tritiated form. The reduced components formed by demethylation were found to readily reoxidize at neutral pH, to regenerate the disulfide bridge. Evidence is provided to show that the two forms were partially interconverted during these steps. The reoxidized 3H-labeled products were found to be indistinguishable in chemical, immunological, and biological properties from the equivalent components in native porcine calcitonin and had specific activities of approximately 20 Ci/mmol. It is concluded that this labeling method can be conveniently applied to peptides containing one or more disulfide bridges, to give products of high specific activity in acceptable yield, provided appropriate conditions are used to ensure correct reoxidation occurs.

Animals↗
PubMed1984

Toxicity of rhizonin A, isolated from Rhizopus microsporus, in laboratory animals.

Maize culture material of 25 isolates of the genera Rhizopus and Mucor caused deaths in day-old unsexed Pekin ducklings when fed as a 50% (w/w) mixture with duckling feed. Nine of these isolates were tested for toxicity in young inbred male BD IX rats, which were fed a mixture of 50% (w/w) culture material and rat feed. Only one isolate of Rhizopus microsporus was clearly toxic, causing 100% mortality in rats within 10 days. Growth in rats was reduced by adding culture material of this isolate to the feed in concentrations of 2.5, 5, 10 or 20% (w/w). The same isolate of R. microsporus was used to produce the mycotoxin rhizonin A. Pure rhizonin A was dissolved in dimethylsulphoxide and given to young male partially inbred albino rats by gavage in single doses of 70, 96, 131 or 180 mg/kg. The lowest dose exceeded the LD100. Evaluated by light microscopy, lesions in livers and kidneys were similar in rats fed culture material and in those intubated with rhizonin A. Hepatocytes showed changes ranging from degeneration to necrosis, the liver-tissue architecture was changed by disassociation of liver cell cords and there was periportal bile-duct proliferation. Renal tubular epithelium showed changes ranging from degeneration to necrosis.

Animals↗
PubMed1984

Synthesis of prostaglandin F by cultured human endometrial cells.

Human endometrial cells were dispersed with collagenase and maintained in culture overnight. The synthesis of PGF by the dispersed cells incubated at 37 degrees C in serum-free medium was stimulated by estradiol (10(-7)M - 10(-5)M), histamine (5X10(-7)M - 5X10(-5)M), bradykinin (10(-6)M), phorbol myristate (PMA, 3X10(-8)M) and arachidonate (5X10(-6)M). Preincubation of the cells for 3 h with cortisol (5X10(-7)M - 5X10(-5)M), progesterone (10(-6)M) or mepacrine (10(-6)M - 2X10(-4)M) inhibited the response to histamine, bradykinin and PMA but not to arachidonate. Perfusion of the cultured cells in filtration chambers yielded similar results to those obtained in the incubation system but differences in the onset and duration of the responses to stimuli were found. In the perifusion system the responses to histamine and bradykinin were rapid and of short duration (peak response in less than 60 min) while the responses to PMA and arachidonate were of longer duration with a slower onset. We conclude that these observations using dispersed endometrial cells are consistent with previous work showing that histamine, bradykinin and PMA act by stimulating acylhydrolase activity, thereby liberating precursors such as arachidonic acid which are converted to prostaglandins by the cyclo-oxygenase complex.

Arachidonic Acid↗
PubMed1984

Inhibition of prostaglandin action and bone resorption by copper.

Mouse calvaria were maintained in organ culture without serum additives. The effects of Cu2+ on bone resorption and on the synthesis and action of prostaglandins were studied. Non-toxic concentrations of copper sulphate (5 microM) were found to decrease active resorption, measured by 45Ca release, to 54% control values (p less than 0.001), while prostaglandin F (PGF), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha, (6-keto-PGF1 alpha), determined by radioimmunoassay, were increased above controls (p less than 0.05). These effects of Cu2+ on prostaglandin synthesis were confirmed by the isolation and quantitation of [3H]-labelled metabolites released from calvaria which had been pre-labelled with [3H]-arachidonic acid. PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) were all higher in copper-exposed calvaria, but their relative amounts remained unchanged. There was no evidence that Cu2+ influenced the mobilisation of [3H]-arachidonic acid from prelabelled calvaria. The stimulation of bone resorption by exogenous prostaglandins was decreased in the presence of Cu2+ (p less than 0.005), while parathormone-mediated bone resorption was virtually unaffected. Cu2+ also increased the inhibition of bone resorption seen with indomethacin (p less than 0.05). In addition to the effects of the metal on prostaglandin action Cu2+ also decreased beta-glucuronidase activity in the media to 86% of the control values (p less than 0.001). The action of Cu2+ in inhibiting bone resorption in vitro appears complex but does not involve inhibition of prostaglandin synthesis. It is likely that Cu2+ has more than one inhibitory locus.

Animals↗
PubMed1984

The effect of diethylhydroxylamine on the incidence of tumors induced by benzo(a)pyrene in the mouse.

Groups of 20 male and 20 female CD-1(ICR)Br mice were treated either with 0, 3, 30, or 300 mg diethylhydroxylamine (DEHA)/kg-day (administered via the drinking water) from 57-112 days of age. For the four week period between 70 to 98 days of age, all animals received (via gavage) eight 1 mg doses of benzo(a)pyrene at 4 day intervals. One hundred thirty-seven animals survived the dosing period. Of these, 132 survived to 211 days of age at which time they were euthanized and necropsied. Gross lesions were observed only in the lungs and squamous portion of the stomach. Treatment with DEHA produced no significant effect on the lung tumor incidence of either sex. However, a significant increase in stomach tumors was observed in the females.

Aging↗
PubMed1983

Dimethonium, a divalent cation that exerts only a screening effect on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes.

Calcium and other alkaline earth cations change the electrostatic potential adjacent to negatively charged bilayer membranes both by accumulating in the aqueous diffuse double layer adjacent to the membrane and by adsorbing to the phospholipids. The effects of these cations on the electrostatic potential are described adequately by the Gouy-Chapman-Stern theory. We report the results of experiments with ethane-bis-trimethylammonium, a cation that has been termed "dimethonium" or "ethamethonium" in analogy with hexamethonium (hexane-1,6-bis-trimethylammonium) and decamethonium (decane-1,10-bis-trimethylammonium). We examined the effect of dimethonium on the zeta potential of multilamellar vesicles formed from the negative lipid phosphatidylserine (PS) and from 5:1 phosphatidylcholine/phosphatidylserine mixtures in solutions containing 0.1, 0.01 and 0.001 M sodium, cesium, or tetramethylammonium chloride. We also examined the effect of dimethonium on the conductance of planar PS bilayer membranes and the 31P NMR signal from sonicated PS vesicles formed in 0.1 M NaCl. We found no evidence that dimethonium adsorbs specifically to bilayer membranes. All the results, except for those obtained with vesicles of low charge density formed in a solution with a high salt concentration, are consistent with the predictions of the Gouy-Chapman theory. We conclude that dimethonium, which does not have the pharmacological effects of hexamethonium and decamethonium, is a useful divalent cation for physiologists interested in investigating electrostatic potentials adjacent to biological membranes.

Bis-Trimethylammonium Compounds↗
PubMed1983

Intakes of copper, zinc, cadmium, tin, iron, nickel and arsenic in a population exposed to lead from water.

Adult diets obtained from a population in Ayr, Scotland, U.K., known to be exposed to lead from water were analysed for arsenic, cadmium, copper, iron, nickel, tin and zinc to assess the intake of these elements. With few exceptions, the concentration of each element varied little from diet to diet, and therefore the range of intakes varied only in proportion to the weights of the diets. With the exception of nickel, the difference between the observed average dietary intakes of the metals studied and those expected on the basis of a nationwide Total Diet Study is largely accounted for on the basis of the differences between the weights of the duplicate diet and the weight for the Total Diet Study.

Adult↗
PubMed1983

The in vitro effect of indomethacin on basal bone resorption, on prostaglandin production and on the response to added prostaglandins.

Mouse calvaria were maintained in organ culture without serum additives. Basal active resorption, as measured by 45Ca and hydroxy-proline release, was significantly inhibited to 74% control levels by indomethacin (1.4 X 10(-7) M). Prostaglandin F and prostaglandin E2 production, determined by radioimmunoassay, were both significantly lowered by this concentration of indomethacin. DNA, protein and hydroxyproline synthesis, as indices of cell toxicity, were unaffected by low concentrations of indomethacin, while concentrations of 1.4 X 10(-6) M inhibited protein synthesis (p less than 0.005). In the presence of indomethacin (1.4 X 10(-7) M) both PGE2 and PGF2 alpha stimulated resorption in a dose-dependent manner, with PGE2 being the more potent. Neither prostaglandin affected hydroxyproline synthesis at low concentrations, but PGE2 had a marked inhibitory action at a higher concentration (10(-6) M). In combination, the effects of PGE2 and PGF2 alpha showed no evidence of synergism or any antagonistic action. The study shows that in vitro calcium and hydroxyproline resorption in the unstimulated mouse calvaria are inhibited by indomethacin at concentrations measured in serum during human therapy. The decreased PGF and PGE2 production associated with this decreased bone resorption in the presence of non-toxic concentrations of indomethacin would suggest a role for these prostaglandins in maintaining the basal resorption of cultured bone.

Animals↗