Search PubMed⌕ Search

Biomedical subjects

S R White

Publications and source records attributed to S R White.

At least 109 records · Page 6Linked to original sources
PubMed1987

Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo.

We studied the contractile response elicited by platelet-activating factor (PAF) administered intra-arterially into the tracheal circulation of 34 dogs in vivo. A method that avoided tachyphylaxis encountered in prior investigations was developed for isometric measurement of multiple dose-response effects. PAF was a very potent contractile agent; active tension was elicited with 10(-11) mol ia PAF. To determine the mechanism by which contraction was induced, dose-response curves were generated in groups of five animals each treated with either 0.5 mg/kg (approximately 1.5 X 10(-5) mol) iv + 10(-3) mg/kg (3 X 10(-8) mol) ia atropine, 5 mg/kg iv indomethacin (INDO), or 7.5 mg/kg iv hexamethonium (HEX). After pretreatment with atropine, contraction still was elicited with 10(-11) mol ia PAF. However, maximal contraction was only 16.2 +/- 2.74 g/cm (vs. 35.7 +/- 5.74 g/cm for untreated controls; P less than 0.02). The dose at which maximal contraction was elicited after atropine was 10(-7) mol ia (vs. 1.9 X 10(-9) mol for controls; P less than 0.001). Pretreatment with INDO caused minimal attenuation, and HEX had no effect on the response elicited by ia PAF. We demonstrate a method for assessing the effects of PAF in central airways that avoids tachyphylaxis and permits dose-response studies in the same animal. We also demonstrate that PAF is an extremely potent mediator that elicits tracheal smooth muscle contraction at least in part by postganglionic activation of parasympathetic nerves. A direct contractile effect of PAF which is not related to secretion of products of the cyclooxygenase pathway is also suggested.

Animals↗
PubMed1987

Homeostatic regulation of airway smooth muscle tone by catecholamine secretion in swine.

We studied the homeostatic secretory response of catecholamine secretion elicited by progressive bronchoconstriction in 18 swine in vivo. The potential reserve of the sympathetic nervous system (SNS) was first assessed by exogenous nicotinic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). A dose of 250 micrograms/kg iv DMPP caused an increase in plasma norepinephrine (NE) concentration from 207 +/- 86 (basal) to 2,625 +/- 448 pg/ml (P less than 0.02) and in plasma epinephrine (EPI) from 10 +/- 5.0 to 1,410 +/- 432 pg/ml (P less than 0.05) in four swine. In four other swine, bronchoconstriction induced by aerosolized prostaglandin F2 alpha caused approximately a fivefold increase in airway resistance without hemodynamic changes. No increase in plasma EPI was observed. However, plasma NE increased from 330 +/- 131 to 1,540 +/- 182 pg/ml (P less than 0.02). In five swine receiving aerosolized acetylcholine (ACh), similar changes in airways resistance were not associated with significant changes in catecholamine concentration when mean arterial blood pressure (MAP) was unchanged. However, inhalation of sufficient ACh to cause a greater than 10% decrease in MAP caused progressive increase in catecholamine secretion. Plasma EPI increased from 32 +/- 16 (MAP = 124 +/- 7 Torr) to 1,165 +/- 522 pg/ml (MAP = 94 +/- Torr). Hypoxemia that occurred with bronchoconstriction (greater than or equal to 50 Torr) did not cause catecholamine secretion. However, severe hypoxemia (PO2 less than 30 Torr) caused large increases in plasma EPI concentrations from 84 +/- 27 to 1,463 +/- 945 pg/ml (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Isoproterenol induced myocardial necrosis is associated with stress protein synthesis in rat heart and thoracic aorta.

Large doses of isoproterenol, which produced macroscopically visible myocardial necrosis, induced the synthesis and accumulation of a 71,000 dalton protein (SP71) in the heart, aorta, and salivary gland of adult male rats. This protein was identical to a protein that has previously been found to be synthesised in the heart in response to heat shock and tissue slicing. Detectable amounts of SP71 were no longer seen five days after the isoproterenol injection, suggesting that this protein accumulates as part of a cellular response to stress and then degrades during tissue repair.

Animals↗
PubMed1986

An approach to mediastinal masses associated with hyperthyroidism.

Benign thymic hyperplasia (BTH) is a known feature of hyperthyroidism, but is infrequently appreciated by clinicians. In most cases thymic enlargement is minimal; however, it may occasionally present as an appreciable anterior mediastinal mass. While surgical resection is a common approach to such a mass, recognition of the benign nature of BTH and its regression following treatment of hyperthyroidism would prevent a major surgical procedure. We present three cases of BTH associated with hyperthyroidism and describe our approach to this syndrome.

Adolescent↗
PubMed1985

A comparison of the effects of serotonin, substance P and thyrotropin-releasing hormone on excitability of rat spinal motoneurons in vivo.

Lumbar spinal motoneurons of urethane-anesthetized rats were driven at stable low firing rates by automatically cycled iontophoretic applications of glutamate or aspartate. The effects of iontophoretically applied serotonin, substance P or thyrotropin-releasing hormone (TRH) on glutamate or aspartate-evoked activity were then tested. All 3 substances were found to enhance both glutamate- and aspartate-induced excitation of the motoneurons. This enhancement of excitability was usually preceded by a brief period of inhibition at current onset. Although the effects of serotonin and substance P were qualitatively remarkably similar, TRH differed in that TRH occasionally inhibited motoneuron excitability without subsequent facilitation, and tachyphylaxis developed for the facilitatory effects of TRH. After TRH desensitization, serotonin could still enhance spinal motoneuron excitability.

Animals↗
PubMed1985

Serotonin and co-localized peptides: effects on spinal motoneuron excitability.

Iontophoretically applied serotonin (5HT), substance P (SP), thyrotropin releasing hormone (TRH) and proctolin all enhanced spinal motoneuron activity evoked by glutamate in urethane-anesthetized rats. 5HT and SP produced more consistent facilitation of excitability both within and between motoneurons than did TRH and proctolin which failed to facilitate several motoneurons. It is concluded that 5TH, SP, TRH and proctolin, which appear to co-exist in various combinations in ventral horn terminals near spinal motoneurons, have complimentary effects on motoneuron excitability.

Animals↗
PubMed1985

Serotonin immunoreactivity in spinal cord axons and terminals of rodents with experimental allergic encephalomyelitis.

Spinal cord axons and terminals stained for serotonin-like immunoreactivity were examined in rats and guinea-pigs with experimental allergic encephalomyelitis, an animal disease model for multiple sclerosis. During the paraplegic stage of experimental allergic encephalomyelitis, many serotonin-positive axons in the ventral and lateral funiculi of both rats and guinea-pigs were found to be grossly distorted, often appearing to end in bulbous enlargements. Serotonin-immunoreactive terminal varicosities in the gray matter were swollen and diminished in number in paraplegic rats with experimental allergic encephalomyelitis. In addition, the intervaricose segments which were observed in control rats appeared to be missing in rats with experimental allergic encephalomyelitis. Depletion of serotonin-positive terminals was much more pronounced in paraplegic guinea-pigs with experimental allergic encephalomyelitis than in rats with experimental allergic encephalomyelitis, but those terminals which remained in the guinea-pigs were morphologically similar to those of control guinea-pigs. The greater depletion of serotonin-positive terminals in guinea-pigs may reflect a more severe disease state in this species, as none of the guinea-pigs survived the acute stage of paralysis. As the time period between recovery from paralysis and sacrifice increased in rats with experimental allergic encephalomyelitis, serotonin-positive terminals in the gray matter became increasingly more normal in appearance. Even by the first day of recovery, some intervaricose segments could again be observed, and after two weeks of recovery, the terminals were much more numerous and less swollen than during the paraplegic stage of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Control of hypertension with nifedipine in the setting of aortic dissection.

We report a 61-year-old man with dissection of the descending aorta and hypertension in whom medical management with beta-blocking antihypertensives was precluded by a history of asthma. The calcium channel blocker nifedipine was successfully employed in this setting and the rationale for its use is discussed.

Aortic Dissection↗
PubMed1983

Pharmacological antagonism of facilitatory but not inhibitory effects of serotonin and norepinephrine on excitability of spinal motoneurons.

Serotonin (5HT) and norepinephrine (NE) produced long-lasting facilitation of glutamate-evoked activity of spinal motoneurons when applied iontophoretically with small ejection currents into the ventral horn. The facilitation was usually preceded by a brief period of inhibition at the onset of current application to the monoamine-containing barrels. This inhibition did not outlast the current application. Ejection of hydrogen ions produced only inhibition of glutamate-evoked activity with no subsequent facilitation at current offset. The 5HT antagonists, methysergide and metergoline, blocked the facilitation, but not the inhibition of motoneuron excitability caused by 5HT. Similarly, the alpha-adrenergic antagonists, piperoxane and phentolamine, blocked the facilitatory, but not the inhibitory, effects of NE on excitability of motoneurons. Since the inhibitory effects of 5HT and NE could not be blocked with the antagonists used, and since ejection of hydrogen ions also produced inhibition, non-specific causes for the inhibitory effects of 5HT and NE could not be rejected. However, the facilitatory effects of 5HT and NE on excitability of motoneurons were readily blocked by antagonists and were, therefore, attributed to actions on separate 5HT and NE receptors in the ventral horn.

Animals↗
PubMed1983

Postnatal development of a cellular response to stress in rat brain.

In vivo synthesis of a stress protein (SP71) in response to hyperthermia was examined in brain and several other tissues from rats ranging in age from 1 day to 25 weeks old. The synthesis of SP71 was increased dramatically by hyperthermia at all ages in all tissues examined except brain. We were unable to detect any increase in SP71 synthesis in brain due to hyperthermia until the rats were more than 2 weeks old. SP71 synthesized by the cerebral microvasculature in response to the trauma of tissue slicing has previously been reported to show a similar requirement for postnatal development. The onset of the increase in synthesis of SP71 in response to either mild hyperthermia or mechanical trauma correlates with the structural and functional maturation of the cerebral microvasculature and the blood-brain barrier.

Age Factors↗
PubMed1983

Norepinephrine depletion in the spinal cord gray matter of rats with experimental allergic encephalomyelitis.

Norepinephrine and dopamine concentrations were determined by radioenzymatic assay in discrete gray matter regions of the spinal cords of rats with experimental allergic encephalomyelitis (EAE). Norepinephrine was depleted in most spinal cord regions of EAE rats compared with controls, whereas dopamine depletion in EAE rats was restricted to the cervical dorsal horn. There was a rostrocaudal gradient of norepinephrine reduction in the spinal cords of the EAE rats with most severe depletion in the lumbar region. The results of this experiment confirmed recent anatomical observations that suggested that catecholamine-fluorescent axons and terminals were damaged in spinal cords of rats with EAE.

Animals↗
PubMed1982

Serotonin-like actions of quipazine and CPP on spinal motoneurones.

The actions of iontophoretically applied quipazine (QPZ) and 6-chloro-2-[1-piperazinyl]-pyrazine (CPP) were compared with those of serotonin (5-HT) on rat spinal motoneurones. QPZ and CPP qualitatively resembled 5-HT in that both facilitated single unit activity evoked by glutamate. Like 5-HT, the facilitation they produced could be antagonized by metergoline or methysergide. These observations are compatible with the suggestion that the actions of QPZ and CPP are mediated by 5-HT receptors. In rats pretreated with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), QPZ and CPP remained effective in facilitating the glutamate evoked activity, whereas p-chloroamphetamine (PCA), a known releaser of 5-HT, was without effect. In contrast, PCA produced a long lasting facilitation in untreated rats. These data, taken together, suggest that QPZ and CPP are direct agonists at 5-HT receptors, but do not preclude the possibility that they might also act indirectly.

5,7-Dihydroxytryptamine↗
PubMed1980

Facilitation of spinal motoneurone excitability by 5-hydroxytryptamine and noradrenaline.

The effects of iontophoretic application of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) on lumbar motoneurone excitability were examined. 5-HT and NA produced long-lasting changes in motoneurone excitability as revealed by decreased threshold for glutamate-evoked motoneurone action potentials, increased rate of motoneurone firing evoked by suprathreshold amounts of glutamate and increased amplitude of ventral root and dorsal root evoked motoneurone field potentials. Neither 5-HT nor NA directly evoked motoneurone action potentials in the absence of other excitatory input. The 5-HT antagonist, methergoline, reduced glutamate-evoked motoneurone activity and prevented 5-HT, but not NA, facilitation of glutamate-evoked activity. These results suggest that 5-HT and NA enhance the effects of excitatory inputs to spinal motoneurones by actions on separate receptors.

Action Potentials↗
PubMed1980

Central serotonin receptor sensitivity in rats with experimental allergic encephalomyelitis.

Serotonin mediated bulbospinal motor activities were examined in rats with experimental allergic encephalomyelitis (EAE)-induced-paraplegia. Treatment with monoamine oxidase inhibitors and L-tryptophan failed to elicit the components of the serotonin syndrome which involved levels of the neuraxis manifesting flaccid paralysis. Straub tail, hindlimb abduction and hindlimb rigidity did not occur. The motor responses represented at spinal segments just above the level of paraplegia, lateral head weaving and forepaw treading, were present but altered in the diseased rats. No impairment was evident in the production of head tremor or hyper-reactivity to accoustic and tactile stimuli. Similarly, in urethane-anesthetized EAE rats, serotonergically-evoked automatic swallowing activity was unchanged as judged by the effects of serotonin receptor agonists, and a serotonin precursor, a reuptake blocker and an antagonist. Our data support the conclusion that EAE-induced impairment of serotonergic neurotransmission is correlated with motor deficits manfested during the acute paralytic stage of the disease.

5-Hydroxytryptophan↗
PubMed1979

Failure of 5-hydroxytryptophan to increase lumbar MSR amplitude in rats paralyzed with experimental allergic encephalomyelitis.

Doses of the 5-hydroxytryptamine precursor, 5-hydroxytryptophan, which markedly increased lumbar monosynaptic response (MSR) amplitude in control rats failed to do so in rats paralyzed with experimental allergic encephalomyelitis (EAE). However, lumbar MSR amplitude could be increased in EAE rats just as in control rats by tetanically stimulating the dorsal root. Post-tetanic potentiation of MSR amplitude occurred in the EAE paralyzed rats both prior to and following 5-hydroxytryptophan injection. It was concluded that, as has been reported for the peripheral system in EAE guinea pigs, central nervous system 5-hydroxytryptamine neurotransmission is impaired, at least in the lumbar spinal cord, in EAE rats with hindlimb paralysis.

5-Hydroxytryptophan↗