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Biomedical subjects

D F Wilson

Publications and source records attributed to D F Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Dependence of carotid chemosensory responses on metabolic substrates.

The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusate flow interruption) were measured (n = 33 carotid bodies). The response to nicotine (n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption (n = 4) and nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate without lactic acid production, O2 chemoreception does not depend on lactic acidosis.

Amino Acids↗
PubMed1992

Effects of hexamethonium on transmitter release from the rat phrenic nerve.

Hexamethonium (HEX) was applied to isolated transected diaphragm-phrenic nerve preparations of the rat in order to further elucidate the functional role of the presynaptic nicotinic autoreceptors. End-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) were recorded from the neuromuscular junctions in the presence and absence of HEX to determine the relative effect of this nicotinic antagonist on end-plate sensitivity and evoked release. In this study we show that HEX enhances transmitter release for the first few stimuli, but this action is not maintained during a train-of-six stimulation. While these results support the hypothesis that transmitter released from the nerve terminal normally has a negative feedback effect by depressing transmitter release it is proposed that HEX also has secondary actions on the neuromuscular junction that are unrelated to autoreceptor blockage. The results with HEX suggests that the presynaptic receptors may differ pharmacologically from the postsynaptic receptors.

Acetylcholine↗
PubMed1992

Localization of tumors and evaluation of their state of oxygenation by phosphorescence imaging.

Oxygen-dependent quenching of phosphorescence has been used to image the distribution of oxygen pressure in small tumors and surrounding tissue. Suspensions of cultured 9L cells or small pieces of solid tumors from 9L cells were injected into the surface of the muscle of the hindquarter of rats, and the tumors were grown until they were 0.2-1.0 cm in diameter. The phosphorescent probe for oxygen was injected into the systemic blood, and phosphorescence was imaged with a video camera. Images of the phosphorescence were collected using a series of different delay times after illumination with a light flash (less than 5-microseconds width at half-height), and the phosphorescence decay constants (lifetimes) and oxygen pressure were calculated for each pixel of the image arrays. The areas of tissue within the tumors were observed to have increased phosphorescence lifetimes and lower oxygen pressures than the surrounding tissue. Phosphorescence imaging is, therefore, a noninvasive optical method which permits quantitation of the distribution of oxygen in small tumors and also, at least in the 9L tumors, differentiation of tumor from normal tissue.

Animals↗
PubMed1992

Monitoring of the oxygen pressure in the blood of live animals using the oxygen dependent quenching of phosphorescence.

Oxygen dependent quenching of phosphorescence is a powerful new method for measuring oxygen pressure in biological systems (see Vanderkooi et al, J. Biol. Chem. 262 (1987) 5476; Wilson et al, J. Biol. Chem. 263 (1988) 2712). This technology has now been extended to include measurements of the phosphorescent of oxygen probes dissolved in the blood as a complex with albumin. In this communication, we report on a new microcomputer controlled phosphorimeter in which the tissue is illuminated by a flash lamp and the phosphorescence observed through flexible light guides designed to make measurements in regions down to approximately 1 mm in diameter. Measurements of the phosphorescence lifetimes of these probes in regions of tissue necessarily report a distribution of oxygen pressures due to the presence of blood in veins and arteriols as well as that present in the capillaries. Thus the phosphorescence decay is the sum of a continuum of exponentials with different decay constants and initial intensities. The complete phosphorescence decay curve is digitized using a 12 bit, 1 MHz A/D board and deconvoluted using numerical methods to yield a distribution of exponentials contributing to the total decay curve.

Animals↗
PubMed1992

The oxygen dependence of mitochondrial oxidative phosphorylation and its role in regulation of coronary blood flow.

The oxygen dependence of mitochondrial oxidative phosphorylation measured in isolated cells of cardiac and non-cardiac origin are affected by the metabolic state of the cells. The contribution of oxygen diffusion to the measured P50 value in resting cells is small. In cardiac myocytes, and possibly in the other cells as well, this contribution may become significant near maximal levels of respiration. The influence of cellular energy metabolism on the oxygen dependence of respiration in cardiac myocytes suggests strongly that mitochondrial oxidative phosphorylation in these cells is an oxygen sensor for adjusting coronary vascular tone during normal cardiac function.

Adenosine Triphosphate↗
PubMed1992

Effect of hyperventilation on oxygenation of the brain cortex of neonates.

A new phosphorescence imaging method (Rumsey et al, Science (1988) 1649) has been used to continuously monitor the oxygen pressure in the blood of the cerebral cortex of newborn pigs. The animals' blood pressure was continuously measured and PaCO2, PaO2 and arterial blood pH were measured periodically. The oxygen pressure in the blood was quantitatively determined for regions of about 100 um square within the image (from a total field of about 3 mm diameter). It was observed that during hyperventilation, which lowered PaCO2 and increased pH of the blood, oxygen pressure decreased in proportion to the decrease in PaCO2. For example, hyperventilation which decreased PaCO2 from its normal value of 40 Torr to 10 Torr caused a rapid (within 5 minutes) decrease in oxygen pressure in the blood of capillaries and veins to approximately 1/4 of normal.

Animals↗
PubMed1992

Oxygen dependent quenching of phosphorescence: a perspective.

Oxygen quenches phosphorescence by energy transfer from the phosphor when oxygen molecules collide with molecules of the phosphor in the excited triplet state. Thus increasing oxygen pressure causes an increase in the rate of decay of phosphorescence (shorter lifetimes) and a decrease in total phosphorescence intensity. Phosphors have been selected which decay with a single exponential and for which the relationship between phosphorescence lifetime and oxygen pressure is quantitatively described by the Stern-Volmer equation. The use of phosphorescence lifetime as the measure of oxygen pressure makes the method insensitive to the absorbance changes of other chromophores in the system. This method has permitted quantitative, rapid (less than 10 msec) and sensitive (to less than 10(-8) Torr) measurements of oxygen pressure in suspensions of cells or subcellular organelles. In tissues, oxygen pressure has been evaluated by measuring phosphorescence using an intensified CCD camera. Maps of oxygen pressure in the vasculature of the cortex of the brain and of other tissues demonstrate the method is limited only by the optics of the system and resolutions of a few microns are readily attained.

Animals↗
PubMed1992

Activation of striatal tyrosine hydroxylase by neurocatin, a neuroregulator from mammalian brain.

Neurocatin, a neuroregulatory factor isolated from mammalian brain, is a powerful affector of dopamine synthesis in striatal rat synaptosomes. Incubation of intact synaptosomes with neurocatin caused an increase in the rate of dopamine synthesis measured by accumulation of DOPA. The increase is rapid (within two minutes) and dependent on the concentration of added neurocatin. The stimulatory effect of neurocatin on dopamine synthesis occurred only in intact synaptosomes and was almost completely abolished by lysis of the synaptosomes with Triton X-100 or sonification prior to neurocatin addition. The kinetic parameters of tyrosine hydroxylase were measured in lysates prepared from synaptosomes preincubated with neurocatin. These showed that with increasing neurocatin concentration there was an increase in Vmax with no significant change in KM for the pteridine cofactor, compared to control. Activation of tyrosine hydroxylase by neurocatin is at least partially caused by a receptor mediated increase in phosphorylation of the enzyme. Protein kinase C and protein kinase II may be involved in this process.

Animals↗
PubMed1992

Tissue responses to Hydron, assessed by intraosseous implantation.

Teflon tubes containing freshly mixed, polymerized Hydron root canal filling material, fully set AH26 or Teflon were implanted into the mandible of guinea pigs and assessed histologically at 2 days, 1, 2, 4, 12 and 26 weeks. None of the materials tested elicited signs of overt or significant tissue damage, and polymerized Hydron was assessed to be as biocompatible as fully set AH26 and Teflon. Bone formed in very close apposition to the polymerized Hydron, whereas a soft tissue capsule separated the regenerated bone from implants of AH26 and Teflon.

Animals↗
PubMed1992

Tissue responses to Hydron, assessed by intramuscular implantation.

Freshly mixed polymerized Hydron root canal filling material, fully set AH26 and Teflon were implanted in the quadriceps muscle of guinea pigs and assessed histologically at 2 days, 1, 2, 3, 12 and 26 weeks after implantation. All materials were characterized by peri-implant fibrous connective tissue capsule formation. Von Kossa-positive calcific material was observed at the implant-tissue interface of Hydron implants. The amount of apparently calcified material increased with time. Inflammation was not a prominent tissue response for any of the test materials, nor was a foreign body giant cell response.

Animals↗
PubMed1992

Effect of hydroperoxy fatty acids on acylation and deacylation of arachidonoyl groups in synaptic phospholipids.

The effect of hydroperoxy fatty acids on reactions involved in the acylation-deacylation cycle of synaptic phospholipids was studied in vitro, using nerve ending fraction isolated from rat forebrain. 15-Hydroperoxyeicosatetraenoic acid (15-HPETE), 13-hydroperoxylinoleic acid (13-HP 18: 2), and hydroperoxydocosahexaenoic acid (22:6 Hpx), at 25 microM final concentration, all inhibited the incorporation of [1-14C]arachidonate into synaptosomal phosphatidylinositol (PI), phosphatidylcholine (PC), and triacylglycerides by 50-80%. The lowest effective concentration of 15-HPETE and 13-HP 18:2 resulting in significant inhibition of the reacylation of PI was 5 microM, whereas the inhibition of [1-14C]arachidonate incorporation into PC required 10 and 5 microM hydroperoxy fatty acids, respectively. Cumene hydroperoxide and tert-butyl hydroperoxide at concentrations of 100 microM did not inhibit reacylation of PI and PC. Synthesis of labeled arachidonoyl-CoA from [1-14C]arachidonate was decreased by about 50% by 25 microM hydroperoxy fatty acids both in synaptosomes and in the microsomal fraction. Use of [1-14C]arachidonoyl-CoA as a substrate, to bypass the fatty acid activation reaction, revealed that activity of acyltransferase was not affected significantly by 25 microM 15-HPETE and 13-HP 18:2. At the same time, however, the hydrolysis of labeled arachidonoyl-CoA was substantially enhanced. Exposure of synaptosomes to 25 microM fatty acid hydroperoxides did not affect significantly the endogenous concentrations of five major free fatty acids. It is concluded that (1) among synaptic phospholipids, reacylation of PI and PC is the most susceptible to the inhibitory action of fatty acid hydroperoxides, and (2) the enzymes affected by these compounds in nerve endings are arachidonoyl-CoA synthetase and hydrolase.

Acylation↗
PubMed1992

Intracellular pH and oxygen chemoreception in the cat carotid body in vitro.

To test the hypothesis that O2 chemoreception in the carotid body (CB) is mediated by cellular acidosis, we simultaneously measured responses of the chemosensory and intracellular pH (pHi) to agents that are known to change pHi and studied the effects of hypoxia and ischemia on these variables in the cat CB. The CB was perfused and superfused in vitro with a modified Tyrode's solution at 36.0 +/- 0.5 degrees C with or without CO2-HCO3- (pH 7.40) and equilibrated at a given PO2. Chemosensory discharges were recorded from the whole carotid sinus nerve. To measure pHi changes, the CB was loaded with the pH-sensitive indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and the fluorescence (excitation 420-490 nm, emission greater than 515 nm) was detected by an intensified charged coupled device camera with an epifluorescence macroscope. Boluses of Tyrode's solution (0.5 ml, free of CO2-HCO3-) containing sodium acetate or NH4Cl prolonged perfusion of acid Tyrode's solution (pH 7.20-6.50), and boluses of Tyrode's solution with CO2-HCO3- were used. A decrease of fluorescence indicated pHi turning acid, and an increase of fluorescence indicated a change in alkaline pHi. Chemosensory activity varied inversely with the fluorescence change after application of these agents. Interruption of perfusate flow or application of hypoxic perfusate resulted in large increases in chemosensory discharge without any change in the fluorescence. The results indicated that chemosensory responses to brief ischemia and hypoxia were not mediated by a fall of pHi of CB cells, whereas those to CO2 and extracellular acidity were associated with decreases in pHi.

Animals↗
PubMed1992

The sensitivity of auditory brainstem response testing in small acoustic neuromas.

Auditory brainstem response (ABR) testing is a reliable and sensitive test for retrocochlear pathology in neurotologic diagnosis. Several investigators have reported the sensitivity of ABR testing as 95% or greater. Fifty-one consecutive patients with surgically confirmed acoustic neuromas were examined. Forty patients had sufficient hearing preoperatively for assessment with ABR. In addition, all had been evaluated with gadolinium-enhanced magnetic resonance imaging and conventional electronystagmography. Overall, 34 of 40 patients (85%) had abnormal ABRs. One of 25 patients with extracanalicular tumors had a normal ABR for a false-negative rate of 4%; however, 5 of 15 patients with intracanalicular tumors had normal ABRs for a false-negative rate of 33%. Tumor size and nerve of origin were important factors affecting the ABR sensitivity. The ABR was less sensitive in detecting intracanalicular tumors than in detecting extracanalicular tumors.

Audiometry, Pure-Tone↗
PubMed1992

Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats.

A newly developed phosphorescence imaging technique was used to generate two-dimensional maps of intravascular oxygen tension (PO2) in the optic nerve head (ONH) and retina of the cat to study the effects of acute moderate increases in intraocular pressure (IOP) on the ONH and retinal PO2. Both the ONH and retinal PO2 were remarkably well maintained as the IOP increased; hypoxia developed only after the blood flow to the eye was stopped. Because ONH hypoxia was not observed during IOP elevation, a lack of oxygen may not be a major cause of glaucomatous damage, although the effects of chronically elevated IOP on the PO2 remain to be evaluated. Because this imaging technique was noninvasive and required only a small bolus injection of a nontoxic oxygen probe, the authors anticipate that it will find significant application in the study of many ocular vascular diseases and glaucoma.

Acute Disease↗
PubMed1991

Neurocatin-induced inhibition of monoamine oxidase A in rat brain synaptosomes.

Neurocatin is a small (about 2000 Da) neuroregulator isolated from mammalian brain. Earlier it was shown that addition of nanomolar concentrations of neurocatin to synaptosomes isolated from rat brain increased levels of serotonin and decreased catabolism of serotonin to 5-hydroxyindoleacetic acid (Fernandez-Novoa L and Pastuszko A. Neurosci Lett 122: 83-86, 1991). In the present study, we report that neurocatin addition resulted in a striking inhibition of monoamine oxidase A activity. This inhibition became statistically significant at a neurocatin concentration of approximately 5 nM and was significant at all higher neurocatin concentrations. Neurocatin at approximately 50 nM inhibited monoamine oxidase A activity by about 90%. The inhibitory effect of neurocatin on monoamine oxidase required its incubation with intact synaptosomes since addition after breaking the synaptosomes by hypotonic buffer or lysis by Triton X-100 almost completely blocked the inhibitory effect. Measurements of the kinetic parameters of the enzyme in lysates prepared from synaptosomes incubated with neurocatin showed a decrease in Vmax with no change in Km for the substrate (serotonin) compared to controls. Incubation of the synaptosomes with approximately 25 nM neurocatin resulted in an 80% decrease in the Vmax of monoamine oxidase A. Evidence that neurocatin is a powerful endogenous modulator of monoamine oxidase activity is particularly intriguing. This enzyme plays a major role in catabolism of the biogenic amines and is believed to contribute to several important neurological disorders.

Animals↗
PubMed1991

Nicotinic receptors on the rat phrenic nerve: evidence for negative feedback.

The effects of low concentrations (nanomolar) of d-tubocurarine (TC) on end-plate potential (EPP) and miniature end-plate potential (MEPP) amplitude, and quantal transmitter release were examined at the rat neuromuscular junction in an attempt to identify the functional role of nicotinic receptors on the nerve terminal. TC (50 and 75 nM) significantly depressed the MEPP amplitude but not the amplitude of the initial EPPs during a train-of-six stimulation at 50 Hz. The lack of depression in EPP amplitude by TC was due to an increase in quantal release. The nearly equipotent response of the pre- and post-synaptic effects of TC suggests that the autoreceptors on the nerve terminal are very similar to the nicotinic receptors on the end-plate. These results suggest that nicotinic autoreceptors are functional even with a single action potential. The results support the hypothesis that ACh released from the nerve terminal normally has a negative feedback effect by depressing transmitter release.

Animals↗