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Biomedical subjects

R A Mitchell

Publications and source records attributed to R A Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1978

Occurrence of an uncoupler-resistant intermediate type of phosphate-water oxygen exchange reaction catalyzed by heart submitochondrial particles.

The hydrolysis of ATP catalyzed by phosphorylating vesicles prepared from bovine heart mitochondria by ultrasonic disruption was studied in H218O. Provided that an ATP-generating system was included to prevent accumulation of ADP due to hydrolysis, the addition of 20 mM arsenate or 0.5 mM 2,4-dinitrophenol to the incubation mixture either singly or together, had little or no effect on the number of oxygen atoms from H2O incorporated (on the average) into each molecule of Pi formed by hydrolysis (the O:P ratio). As the ATP concentration was reduced from 2.0 to 0.05 mM, the O:P ratio increased from about 1.4 to over 2.0 and, although dinitrophenol significantly increased the ATPase activity, it did not significantly alter the O:P ratio for a given ATP level. This implies that the uncoupler does not act directly on the terminal transphosphorylation step. Companion experiments were performed in which 18O label was placed either initially in H2O or Pi. Under conditions where extensive exchange from H218O into Pi occurred, no 18O was lost from medium Pi under identical circumstances, thus showing that the exchange was intermediate and did not involve medium Pi. Kinetic plots of v vs. v/S were nonlinear with respect to ATPase activity. The kinetic data, as well as the Pi = H218O exchange data, are consistent with enzyme models having multiple forms of catalytic sites. Several models are evaluated and attempts are made to distinguish between some of the simpler cases of these models.

Adenosine Triphosphate↗
PubMed1978

Properties of apneusis produced by reversible cold block of the rostral pons.

Reversible cold block of the rostral pons was used to compare properties of normal and apneustic respiration in anesthetized, vagotomized, artificially ventilated cats. During apneusis we observed high frequency oscillations (HFO) in phrenic nerve activity which were reduced in frequency compared with those during a normal inspiration. Apneusis produced by mid-pontine transection or punctate pneumotaxic center (PC) lesion produced similar HFO changes. The minimal intensity of superior laryngeal nerve electrical stimulation needed to terminate a breath was higher early in an apneusis than at the same time during a normal breath. Later in apneusis the intensity required became constant and was approximately the same as that needed to end a normal inspiration at its natural termination. With intact vagi lung inflation produced a greater prolongation of expiration during apneustic respiration than during normal respiration. Apneustic type activity was observed in both phrenic and vagal inspiratory motoneurons. We suggest that: (1) HFO are generated without the PC, but the PC elevates the oscillation frequency; and (2) apneusis may result in part from a delayed activation of the normal inspiratory off-switch mechanism.

Action Potentials↗
PubMed1977

Neural regulation of respiration.

During the last decade, we have seen our knowledge of the neural regulation of respiration progress from the concept of "respiratory centers" to that of densely packed groups of respiratory neurons located within specific medullary nuclei. By careful neurophysiological and histological studies employing intra- and extracellular recording, the sequence of processing of afferent information through these nuclei and the axonal projections from respiratory neurons have been determined. However, the site and the mechanism of respiratory rhythm generation remain unknown.

Animals↗
PubMed1977

Erythrocyte porphobilinogen synthase (delta-aminolaevulinate dehydratase) activity: a reliable and quantitative indicator of lead exposure in humans.

We assessed optimal conditions for assay of porphobillinogen synthase (EC 4.2.1.24) activity in human blood containing abnormally high concentrations of lead. Zn2+and -SH, both required for complete activation of the enzyme, had additive effects. Using a modified method based on these studies, we found blood lead concentration to be strictly proportional to ln(activated/nonactivated) enzyme activity. One brand of commercially available "lead-free" tubes contained a substance that interfered with this relationship. In vitro studies, with the modified assay, showed ALAD to be activated by low concentrations but inactivated by high concentrations of Hg2+, Cd2+, and ethylenediaminetetraacetate. We fouund no genetically influenced differences among unexposed individuals when in(activated/nonactivated) enzyme activities were compared. The technique is suitable for use in screening for lead poisoning in humans.

Cadmium↗
PubMed1976

Lateralized phrenic nerve responses to stimulating respiratory afferents in the cat.

We stimulated electrically pharyngeal branch of both glossopharyngeal nerves (PGLN), internal branch of superior laryngeal nerves (ISLN), and carotid sinus nerves (CSN) in anesthetized cats. We recorded simultaneously, averaged, and compared bilaterally evoked phrenic nerve (PHR) activity. Our objective was to demonstrate a short-latency evoked response in the PHR contralateral to the stimulus. Low-intensity stimulation of PGLN and ISLN during inspiration evoked a short-latency contralateral excitation with a latency of 5.2 ms +/- 0.2 SE (16 cats) for PGLN, and 3.8 ms +/- 0.1 SE (13 cats) for ISLN. This excitation could follow stimuli delivered at 100 Hz. Stimulation during expiration did not result in a lateralized excitation. The excitation is followed by bilateral inhibition. Neither strychnine nor picrotoxin prevented either the lateralized response or the inhibition, though strychnine diminished a delayed bilateral excitation following PGLN stimulation. This dalayed (latency 18.7 ms +/- 0.7 SE) bilateral excitation corresponds to the sniff reflex. CSN stimulation did not result in lateralized excitation. We suggest that the lateralized evoked response results from a gated paucisynaptic reflex pathway involving the PGLN and ISLN, ipsilateral inspiratory neurons, and contralateral PHR motoneurons.

Animals↗
PubMed1975

The effects of ADP on reverse electron flow and the oxygen exchange reactions catalyzed by bovine heart muscle submitochondrial particles.

1,N6-Ethenoadenosine diphosphate (epsilon-ADP) inhibits reverse electron flow (succinate leads to NAD+ driven by ATP) by competing with ATP, in contrast to ADP which we have shown previously to be a noncompetitive inhibitor. From these and other data it is concluded that the noncompetitive inhibition noted with ADP results from a combination of competitive inhibition plus non- or uncompetitive inhibition, the former occurring at a relatively nonspecific catalytic site and the latter at an extracatalytic site apparently quite specific for ADP. ADP, which stimulates ATP in equilibrium H2O and Pi in equilibrium H2O exchanges appears to be necessary for inhibition by arsenate of these exchanges. It is suggested that the ATP-supported Pi in equilibrium H2O exchange may be predominantly of the medium or intermediate type, depending on the concentrations of the Mg2+ complexes of ADP and Pi. Thus only exchanges involving medium ADP and Pi would be expected to show arsenate sensitivity.

Adenosine Diphosphate↗
PubMed1975

Potencies of doxapram and hypoxia in stimulating carotid-body chemoreceptors and ventilation in anesthetized cats.

The effects of doxapram on carotid chemoreceptor activity and on ventilation (phrenic-nerve activity) were tested before and after denervation of the peripheral chemoreceptors in cats. Doxapram was found to be a potent stimulus to the carotid chemoreceptors; the stimulation produced by 1.0 mg/kg doxapram, iv, equalled that produced by a Pao2 of 38 torr. Doxapram also increased phrenic-nerve activity in doses as low as 0.2 mg/kg, iv. After denervation of the peripheral chemoreceptors, doxapram in doses as large as 6 mg/kg failed to stimulate ventilation. It is concluded that (in anesthetized cats) doxapram in doses of less than 6 mg/kg increases ventilation by direct stimulation of the carotid, and, probably, the aortic, chemoreceptors, not by a direct effect on the medullary respiratory center.

Anesthesia↗
PubMed1975

Neural regulation of respiration.

The main respiratory muscles are under both voluntary and involuntary (automatic) control. These two control systems come from separate sites in the CNS and have separate descending pathways; the final integration of these outputs occurs at segmental levels in the cord. Voluntary control arises from the motor and premotor cortex and descends in the cord in the corticospinal tract. Involuntary control is mediated by both rhythmic and nonrhythmic systems located in the brainstem. Recent studies have associated the classic respiratory centers with specific nuclei in the brainstem. The pneumotaxic center is located in the nucleus parabrachialis, and the medullary respiratory centers are located in the vicinity of the nucleus of the solitary tract (dorsal respiratory group) and the nuclei ambiguus and retroambigualis (ventral respiratory group). Most axons from the medullary nuclei cross in the medulla and descend in the ventral and lateral columns to segmental levels. The classic medullary respiratory centers described by Pitts have been shown to be the site of origin of tonically firing long reticulospinal axons that descend in the ventral and lateral columns. This system is thought to provide a nonrhythmic involuntary biasing of the membrane potential of respiratory motoneurons in the cord. The site of generation of eupnic breathing and the mechanism of rhythm generation remain unknown. However, recent studies indicate that reciprocal inhibition between populations of inspiratory and expiratory cells (bistable oscillator model) does not occur in the medulla; rather we suggest that inhibitory phasing of inspiratory cells generates inspiratory rhythm, and periodic inhibition of tonically active expiratory neurons results in respiratory rhythm. We suggest that the inhibitory phasing occurs in the dorsal respiratory group, which is also the site of integration of respiratory afferents. The main site of integration of the voluntary and involuntary control systems is the cord where the respiratory motoneuron output is determined by descending information from these systems, as well as with intrasegmental and intersegmental reflexes. Separation of the voluntary and involuntary control systems also occurs in man and discrete lesions may interrupt one system without significant alteration of the other.

Animals↗