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Biomedical subjects

A P Smith

Publications and source records attributed to A P Smith.

At least 19 recordsLinked to original sources

Effects of oral H1 and H2 receptor antagonists in asthma.

1 There is evidence that H2 receptors are present in the lung, both on bronchial smooth muscle and mast cells. In animal studies, stimulation of H2 receptors causes a diminution, and conversely H2 receptor blockade can increase, smooth muscle contraction and mediator release. 2 The effects of H2 receptor blockade in ten patients with asthma has been studied using oral cimetidine in a dose of 1 g daily for 1 week. Treatment was compared with placebo and the H1 receptor antagonist chlorpheniramine. 3 There was no alteration in the severity of naturally-occurring or exercise-induced asthma with cimetidine or chlorpheniramine. 4 H2 receptor blockade with oral cimetidine in conventional doses is without ill effect in asthma. The use of larger parenteral doses is discussed.

Adolescent

Bronchial secretion from normal human airways after inhalation of prostaglandin F2alpha, acetylcholine, histamine, and citric acid.

Sputum produced by normal subjects after inhalation of prostaglandin F2alpha, acetylcholine, histamine, and citric acid has been analysed. Prostaglandin F2alpha was the most effective of the drugs in promoting sputum production. The material expectorated after inhalation of prostaglandin F2alpha shows the characteristics of mucoid sputum from patients with chronic bronchitis. The apparent viscosity and the concentration of marker substances for bronchial glycoprotein was in the lower part of the range found in mucoid chronic bronchitic sputum. The concentration of marker substances for serum glycoproteins and tissue fluid transudate were below the range found in chronic bronchitis, indicating that, in disease states, in addition to bronchial mucus there is a marked tissue fluid transudate component. Sputum produced after inhalation of acetylcholine and histamine contained relatively more tissue fluid transudate than sputum produced after inhalation of prostaglandin F2alpha, Sputum produced after inhalation of prostaglandin F2alpha, is of special value in indicating the nature of secretion from normal airways.

Acetylcholine

Airway response to carbachol in normal and asthmatic subjects: distinction between bronchial sensitivity and reactivity.

By constructing cumulative dose-response curves to inhaled carbachol in 12 normal and 17 asthmatic subjects with comparable baseline specific airway conductance, we have shown that there were wide variations among subjects in the dose of carbachol needed to cause a 25 per cent decrease in specific airway conductance (bronchial sensitivity) and in the slopes of the curves (bronchial reactivity). Furthermore, there was no significant correlation between these 2 characteristics of the bronchial response to carbachol. The mean dose-response curves of the asthmatic and the normal subjects were widely divergent, indicating that the asthmatic subjects differed from normal subjects more in terms of bronchial reactivity than in bronchial sensitivity. This suggests that different mechanisms determine the sensitivity and reactivity of the bronchial tree, and that hyper-reactivity is the main feature of the asthmatic response. Both should be assessed when the bronchial response to bronchoconstrictor agents is measured.

Asthma

The effect of pH on stereospecific opiate binding to mouse brain membranes.

High-affinity, in vitro stereospecific binding of 3H-di-hydromorphine or 3H-naloxone to brain membranes shows a marked dependence on pH; maximal binding, observed at pH 7.5-8.0, is abruptly and reversibly reduced as the pH is lowered, with the binding half-maximal at about pH 6.8. A similar pH dependence of stereospecific binding is observed with the quaternary agonist N-methyl morphine, but non-specific 3H-di-hydromorphine of 3H-naloxone binding (that not displaced by a 100-fold excess of unlabelled levorphanol) shows only a slight decrease in this pH range. Binding of agonist and antagonist at pH 6.8 show the same differences with respect to trypsin sensitivity and to the effects of Na+ and Mn++ ions that are seen at pH 8.0. It is concluded that the ability of low pH to reduce stereospecific binding is due to protonation of a membrane-bound site, and that this site is probably the anionic site of the opiate receptor. Of the four anionic groups commonly found in biological membranes, only phosphate exhibits a pK close to that of this effect. Taken with other evidence, the results suggest that the opiate receptor may be a phosphoprotein.

Animals

The response of normal and asthmatic subjects to prostaglandins E2 and F2alpha by different routes, and their significance in asthma.

Although PGE2 and PGF2alpha have potent effects on the human bronchus by aerosol, they are less potent when given by the intravenous route. Prostaglandin E2 may cause bronchoconstriction. Indomethacin had no effect on day-to-day asthmatic symptoms, or challenge-induced asthma, suggesting that prostaglandins are not fundamental to the pathogenesis of asthma.

Adolescent