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Biomedical subjects

M R Montgomery

Publications and source records attributed to M R Montgomery.

At least 55 records · Page 3Linked to original sources
PubMed1981

Hydrogen peroxide contracts airway smooth muscle: a possible endogenous mechanism.

Both distal (canine lung strips) and proximal (bovine trachealis strips) airway smooth muscle contract in isolated organ baths as the percentage of environmental oxygen is increased from 12% to 95%. This effect is blocked by prostaglandin synthetase inhibitors (indomethacin, 10(-4)M; meclofenamate, 10(-4)M). To determine whether this contractile response is due to molecular oxygen, or to other products of oxidative metabolism, we examined the effects of ozone, hydrogen peroxide, and superoxide radical generating systems (paraquat and xanthine-xanthine oxidase) on the smooth muscle preparations. Ozone (3 ppm), paraquat (2 mM), and xanthine (10(-3)M)-xanthine oxidase (1 unit) were without effect. Hydrogen peroxide (10(-5)-10(-3)M) produce consistent contractions in both preparations, an effect which was appreciably greater in an hypoxic environment and which was blocked by both indomethacin and meclofenamate. Contraction from both hyperoxia and hydrogen peroxide was partially reversed by various oxygen radical scavengers, including methional (10 mM), ascorbic acid (10 mM), nitroblue tetrazolium (0.3 mM), butylated hydroxyanisole (1 mM), and 2',7' naphthalonediol (1 mM). These results suggest that hyperoxic contraction in airway smooth muscle is mediated by active oxygen species, perhaps by their effects on prostaglandin metabolism.

Animals↗
PubMed1981

Bleomycin inhibits hepatic mixed function oxidation.

Bleomycin inhibits hepatic microsomal ethylmorphine N-demethylase activity in both the athymic (nude) mouse and the rat four days after a single injection. This inhibition occurred both with subcutaneous and intraperitoneal injections. With multiple dose chronic treatment, s.c. injections resulted in decreases in both enzymatic activity and cytochrome P450 concentration in both species. However, i.p. chronic injection resulted in decreases only in the rat.

Animals↗
PubMed1980

Oxygen effects of metabolism and paraquat uptake in rat lung slices.

Paraquat accumulation into rat lung slices was unaffected by hypoxia (PO2 = 645 mm Hg) but was inhibited by hypoxia. The IC50 (IC50 = partial pressure of O2 resulting in a 50% inhibition of paraquat accumulation) for paraquat accumulation was P02 = 50 mm Hg; significant accumulation could be observed after 1 or 2 hr of incubation at PO2 = 10 mm Hg. The hypoxic inhibition was due to oxygen limitation of the accumulation mechanism and not to a diffusion limitation of oxygen or to cell death. Incubation of lung slices for up to 2 hr in 100% N2 (PO2 = 0 mm Hg) did not decrease paraquat accumulation or metabolism of glucose to CO2 when the slices were returned to room air. However, under the same conditions total tissue oxygen consumption was decreased by 50%. Paraquat accumulation and glucose metabolism are oxygen dependent but are resistant to the damaging effects of cellular anoxia.

Animals↗
PubMed1979

Mechanisms of airway smooth muscle response to isoproterenol and theophylline.

Airway smooth muscle preparations from various sites and species exhibit a range of sensitivities to the same beta-adrenergic agonist. This variability has been attributed to beta-receptor function but the exact mechanism determining the response has not been identified. After first inducing contraction with acetylcholine, we measured isoproterenol and theophylline relaxation responses in five separate airway smooth muscle preparations in vitro. The order of sensitivity was identical for both drugs: guinea pig trachea greater than dog lung strip greater than dog bronchiole greater than rat trachea greater than dog trachea. Because of evidence that both drugs act by increasing adenosine 3',5'-cyclic monophosphate (cAMP) concentrations, we utilized a kinetic model of cAMP metabolism to investigate the possibility that the identical order of sensitivity to both drugs could be explained by a common mechanism. Relaxation responses to both drugs are in accord with known kinetic data. Small differences in the velocity constants of enzymes affecting cAMP metabolism or differences in the relaxation response to the same concentrations of cAMP can fully explain the variable muscle responses to both drugs.

Animals↗
PubMed1979

Oxidant-induced alterations in pulmonary microsomal mixed-function oxidation: acute effects of paraquat and ozone.

Pulmonary mixed function oxidations are altered by in vivo exposure to paraquat or ozone. The cytochrome P-450-mediated benzphetamine N-demethylase activity was inhibited by low doses of both oxidants (paraquat, 20 mg/kg, ip; ozone, 1 ppm, 24 hrs). The effect of paraquat did not appear until 4 days after treatment and was still apparent after 2 weeks. The inhibition following exposure to ozone appeared immediately (1 day) and had resolved by one week. Cytochrome b5-mediated lipid desaturation was unaffected by the paraquat treatment and was stimulated by ozone. These alterations in pulmonary mixed function oxidase activities could not be explained by microsomal lipid peroxidation. The concentrations of cytochromes P450 and b5 also did not accurately reflect the altered enzymatic activities. The sites of the paraquat- and ozone-mediated alterations are still unknown.

Animals↗
PubMed1977

Human intoxication following inhalation exposure to synthetic jet lubricating oil.

A previously healthy member of an aircraft flight crew was acutely incapacitated during flight with neurologic impairment and gastrointestinal distress. His clinical status returned to normal within 24 hr. The etiology of his symptoms was related to an inhalation exposure to aerosolized or vaporized synthetic lubricating oil arising from a jet engine of his aircraft.

Adult↗
PubMed1977

Paraquat toxicity and pulmonary superoxide dismutase: an enzymic deficiency of lung microsomes.

Paraquat stimulates the microsomal generation of superoxide radical, O2-, and hydrogen peroxide, H2O2. The detoxification of these two oxidants is accomplished by superoxide dismutase (SOD) and catalase, respectively. SOD activity could not be detected in lung microsomes but was found in microsomes of both kidney and liver. This deficiency may be involved in the pulmonary specificity of paraquat.

Animals↗
PubMed1976

Characterization of fatty acid desaturase activity in rat lung microsomes.

Preparations of rat lung microsomes containing 0.030-0.050 nmole of cytochromes P-450 and b5 per mg microsomal protein have been observed to contain significant levels of fatty acid desaturase activity. Both stearoyl CoA and palmitoyl CoA are desaturated to their monounsaturated analogues, oleic acid and palmitoleic acid, respectively. Activity (per mg microsomal protein) of the lung preparations varied according to the diet of the animals prior to killing in the order: fat free diet greater than normal rat chow greater than starvation. All preparations exhibited approximately 50% inhibition when incubated in the presence of 0.10 mM CN-. Maximal activity was obtained with the 0.50 mM NADH less activity with equal amounts of NADPH, and there was no synergistic interaction of NADH and NADPH together. The rate of desaturation was linear with protein concentrations between 0.15-1.5 mg microsomal protein/incubation at incubation times up to 8 min. A pH optimum range of 7.0-7.4 was observed. For all variables of fatty acid desaturase activity which were examined, the rate of desaturation of stearoyl CoA was approximately twice that for palmitoyl CoA. These results indicate that the same fatty acid desaturation system which is functional in the liver is also present in significant amounts in mammalian lungs.

Animals↗
PubMed1976

A compact, versatile inhalation exposure chamber for small animal studies.

An inhalation exposure chamber was designed to fit conveniently into a standard laboratory exhaust hood. The chamber was constructed entirely of non-corrosive materials and was suitable for continuous exposure of 6 small laboratory animals to corrosive atmospheres such as ozone. A separate, outer chamber surrounding a smaller, inner chamber permitted access to each individually housed animal without disturbing the experimental atmosphere. Facilities were available for ad libitum access to food and water for chronic exposures. The chamber was easily disassembled for cleaning. A safety mechanism was described which automatically stops the generation of a toxic gas in the event of an exhaust system failure.

Animals↗