Effects of sleep on the pattern of CO2 stimulated breathing in males and females.
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Biomedical subjects
Publications and source records attributed to J N Davis.
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A computer-assisted method is developed for analyzing volume and time components of individual breaths using a previously developed magnetometer method for recording anteroposterior (AP) diameters of rib cage and abdomen. Calibration constants for the magnetometer system are computed during simultaneous measurements of airflow at the mouth for several breaths during spontaneous breathing. Tidal volume and inspiratory and expiratory times can then be computed from the magnetometer signals alone, without imposing respiratory devices at the subject's airway. No respiratory isovolume maneuvers are necessary. Results from normal subjects and from one patient with bilateral diaphragmatic paralysis show that the magnetometer analysis is closely comparable to standard measurements made from airflow recordings. The magnetometer technique thus provides an accurate means of measuring volume and time components of breathing in man, avoiding the behavioral or reflex effects induced by mouthpiece, nose clip, or face mask. Because no special respiratory maneuvers are required for calibration, the technique will be well suited to the study of breathing in those who are ill.
Alpha adrenergic stimulation elicits a rapid release of K+ from dispersed rat parotid cells. Surprisingly neither clonidine, oxymetazoline, naphazoline, ST 600 nor ST 91 elicited K+ release from parotid cells at concentrations up to 100 micrometer. By contrast, these agents were able to block epinephrine-stimulated K+ release with the relative potencies: oxymetazoline more than naphazoline more than clonidine more than ST 600 more than ST 91. [3H]-Dihydroergocryptine (DHE) binds to sites on parotid membranes and intact dispersed cells with the characteristics of alpha adrenergic membrane receptors. The ability of these imidazolines to displace [3H]DHE binding from parotid membranes correlated with their potencies as alpha adrenergic antagonists in the dispersed cells. Although clonidine, oxymetazolin and naphazoline are agonists in other peripheral alpha adrenergic receptors, they are antagonists in the parotid. This observation explains the most common side-effect of clonidine administration, dry mouth, and is consistent with the proposition that different groups of alpha adrenergic receptors exist in mammalian tissues. These data also suggest that the central actions of clonidine must be interpreted with caution since alpha adrenergic receptors similar to those in the parotid may be present in brain.
[3H]dihydroergocryptine (DHE) appears to bind to alpha-adrenergic receptor sites in rabbit uterine membranes. We have characterized the binding of [3H]DHE to membranes prepared from rat cerebral cortex. alpha-Adrenergic agents were less potent and dopamine and serotonin, more potent, in displacing brain DHE binding than in uterus. Furthermore brain DHE binding sites demonstrated less stereospecificity for catecholamines than sites in uterus. Dopamine displaced DHE binding with about the same potency in cerebellar and cerebral cortical membranes, but was 10 times as potent in displacing DHE binding in the striatum. The binding of [3H]DHE in brain is complex and differs significantly from the rabbit uterus. There are two possible explanations for this discrepancy. [3H]DHE may bind a single site in brain with properties differing from known peripheral adrenergic receptors or DHE may bind to multiple sites in brain, sites which may or may not represent other neurotransmitter receptors.
A single electroconvulsive shock (ECS) was applied to 40 young (9 months) and 40 old (24 months) male rats. The effect on brain catecholamine synthesis was determined at intervals after ECS by measuring the accumulation of dihydroxyphenylalamine (DOPA) and 5-hydroxytryptophan (5-HTP) in rats pretreated with a central decarboxylase inhibitor (M-hydroxybenzyl hydrazine, NSD 1015). This accumulation permitted an estimation of the in vivo rates of hydroxylation of tyrosine and tryptophan. Control brain DOPA and 5-HTP concentrations were both lower in the older animals. Following ECS there was an increase in brain DOPA concentration (maximal at 60 min after ECS) in both young and old rats, but the increase was much smaller in the older animals. There were no changes in brain 5-HTP at any time after ECS, in either age group. It appears that aging selectively affects the response of the brain dopaminergic neurotransmitter system to stress, and we suggest that this may be a factor in the decreased resistance to stress in older subjects.
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Paralysis or severe weakness of the diaphragm (the principal muscle of inspiration) is commonly associated with hypoventilation which may be profound during sleep, but the disorder is often unrecognized. The clinical sign of paradoxical (inward) movement of the abdominal wall during spontaneous inspiration in the supine posture may be overlooked, or the appearances at fluoroscopy may mislead, for it is not generally appreciated that descent of the diaphragm in early inspiration in these patients may be an entirely passive event. Measurement of transdiaphragmatic pressure is a simple, reliable and quantitative means of assessing diaphragm function, and will aid in the diagnosis of diaphragm paralysis which has important implications for clinical management.
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Pulmonary mechanics and respiratory muscle pressures were studied in 7 patients with severe respiratory muscle weakness. Minimal pleural pressures were grossly abnormal and showed little variation with lung volume. Both the maximal transpulmonary pressure and static expiratory compliance were low; therefore, the pressure-volume curves of the lungs resembled those obtained after strapping the chest in normal subjects. The low compliance may result from either microatelectasis or a generalized alteration in alveolar elastic properties and is probably a major determinant of both the total lung capacity and the breathing pattern of patients with neuromuscular disease. Airway and gas exchange function were less abnormal than the elastic properties of the lungs.
The concentrations of DOPA and 5 hydroxytryptophan in rat brain were decreased by freezing on dry ice rather than in liquid nitrogen, and by a 5 minute delay in removing and freezing the brain by either method. The effect of post-mortem delay in freezing was greater for 5 HTP than for DOPA.
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Escherichia coli contains two glutaminases, A and B, with pH optima below pH 5 and above pH 7, respectively. Neither glutaminase A nor B is released from E. coli by osmotic shock. Glutaminase B has been purified 6,000-fold and the purified preparation is estimated to contain about 40% glutaminase B. The enzyme has a molecular weight of 90,000 and an isoelectric point of 5.4. Glutaminase B exhibits a broad pH optimum between 7.1 and 9.0. Only L-glutamine is deamidated by glutaminase B, L-asparagine and D-glutamine are not deamidated. The substrate saturation curve for glutaminase B shows an intermediary plateau region. Like many regulatory enzymes, glutaminase B is cold-labile. The enzyme is inactivated by cooling and activated by warming; both processes are first order with respect to time. The activation energy for activation by warming was calculated to be 5900 cal/mol. Activation by warming increased the Vmax and decreased the S0.5 for L-glutamine, but did not alter the molecular weight of the catalytically active enzyme. Borate and glutamate protected glutaminase B from inactivation by cold.
Seven weeks after he was bitten on the lip by a puppy in the Gambia a patient showed symptons of rabies. Passive and active immunisation was begun three days after the onset of symptons. The evidence indicated that death was a direct consequence of the central nervous system disease rather than any associated complication. Our inability to alter the course of the illness appreciably emphasises the importance of immediate postexposure immunisation in rabies and draws attention to the present lack of effective means of preventing virus replication within the central nervous system.
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A small, heat-stable selenoprotein, one of the components of the glycine reductase complex, was labeled with 75Se by growth of Clostridium sticklandii in the presence of Na2 75SeO3. The selenium-containing moiety, which is essential for the biological activity of the protein, was shown to be a selenocysteine residue. It was isolated as its Se-carboxymethyl, Se-carboxyethyl, and Se-aminoethyl derivatives from digests of the pure 75Se-labeled protein that had been reduced and treated with the various alkylating agents prior to hydrolysis. In each instance the 75Se-labeled moiety obtained from an alkylated protein sample and the corresponding alkyl derivative of authentic selenocysteine were indistinguishable. Several studies of the native selenoprotein detected a chromophore (UVmax 238nm) that appeared upon reduction of the protein with KBH4 and rapidly disappeared upon exposure to oxygen. This oxygen-labile chromophore is thought to be the ionized -SeH group of the selenocysteine residue.