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Biomedical subjects

T J Murphy

Publications and source records attributed to T J Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1991

Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line.

The alpha-2 adrenergic receptors have been subdivided into two pharmacological subtypes known as alpha-2A and alpha-2B. The OK cell, a cell line derived from an opossum kidney, expresses an alpha-2 adrenergic receptor which has pharmacological characteristics different from both the alpha-2A and alpha-2B subtypes, and thus may be a third subtype. To test this hypothesis, we compared the affinities (Ki values from radioligand binding) of 49 drugs in the OK cell with their affinity for the alpha-2A (HT-29 cells) and alpha-2B (neonatal rat lung) adrenergic receptor subtypes. Eight drugs (spiroxarine, prazosin, WY 27127, L-657,743, ARC 239, akuammigine, rauwolscine and oxymetazoline) were identified whose Ki differed by 10-fold or more between the OK cells and HT29 cells. Five drugs (BAM 1303, raubasine, WB 4101, akuammigine and rauwolscine) differentiated, by at least 10-fold, between OK cells and neonatal rat lung. Correlations of pKi values between the OK cell and tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes were poor, confirming that the OK cell receptor could not be classified as either alpha-2A or alpha-2B. In contradistinction, there was a good correlation between pKi values for the OK cell line and opossum kidney showing that they express the same subtype. In addition, ratios of subtype-selective drug Ki values were similar for the OK cell and opossum kidney, but different from other tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes. We conclude that the OK cell line and opossum kidney express a novel subtype of alpha-2 adrenergic receptor which we term the alpha-2C subtype.

Animals↗
PubMed1990

Determination of iodine in oyster tissue by isotope dilution laser resonance ionization mass spectrometry.

The technique of laser resonance ionization mass spectrometry has been combined with isotope dilution analysis to determine iodine in oyster tissue. The long-lived radioisotope, 129I, was used to spike the samples. Samples were equilibrated with the 129I, wet ashed under controlled conditions, and iodine separated by coprecipitation with silver chloride. The analyte was dried as silver ammonium iodide upon a tantalum filament from which iodine was thermally desorbed in the resonance ionization mass spectrometry instrument. A single-color, two-photon resonant plus one-photon ionization scheme was used to form positive iodine ions. Long-lived iodine signals were achieved from 100 ng of iodine. The precision of 127I/129I measurement has been evaluated by replicate determinations of the spike, the spike calibration samples, and the oyster tissue samples and was 1.0%. Measurement precision among samples was 1.9% for the spike calibration and 1.4% for the oyster tissue. The concentration of iodine determined in SRM 1566a, Oyster Tissue, was 4.44 micrograms/g with an estimate of the overall uncertainty for the analysis of +/- 0.12 microgram/g.

Animals↗
PubMed1989

Planning abilities in alcoholics, process and reactive schizophrenics, and normals.

This study investigated planning abilities in alcoholics, process and reactive schizophrenics, and normals. Significant differences among the groups were found on all three planning tasks. Normals and alcoholics showed significantly greater planning ability on the picture arrangement task than the process schizophrenics. On the maze task, normals attained significantly higher scores than the process schizophrenics. On a task in which subjects predicted future effects from a present-day trend, alcoholics showed significantly greater planning ability than normals and process schizophrenics. Reactive schizophrenics did not differ significantly from any of the other groups on any task. The greater planning ability of the alcoholics in comparison with the normals on one of the tasks may be due to sampling and situational differences. The results suggest that deficits in planning abilities are temporary for alcoholics.

Adaptation, Psychological↗
PubMed1989

Characterization of serotonin-1B receptors negatively coupled to adenylate cyclase in OK cells, a renal epithelial cell line from the opossum.

We have previously reported the presence of a 5-HT1 (serotonin)-like receptor coupled in an inhibitory manner to adenylate cyclase in the opossum kidney cell line, which is derived from the kidney of a North American opossum. Pharmacological data from binding and cyclic AMP production studies indicate that this receptor does not have characteristics of a 5-HT1A, 5-HT1C or 5-HT1D receptor, but is similar to 5-HT1B receptors found in rodent tissues. Many serotonergic drugs, including 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyrindinyl)1H-indol, 5-HT and methysergide, but not (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide or buspirone, were full agonists at this receptor as defined by the inhibition of bovine parathyroid hormone peptide fragment 1-34-stimulated cyclic AMP production in an intact cell assay. Several classical beta adrenergic antagonists including propranolol and cyanopindolol were also full agonists at this receptor. Radioligand binding studies using [125I](-)-iodocyanopindolol gave a Bmax of 88 fmol/mg of protein and a KD of 47 pM for saturation experiments carried out in the presence of GTP. In the absence of GTP, the binding data were significantly better fit by a two-site model with KD values of 10 and 345 pM. Inhibition binding experiments were consistent with the results of the cyclic AMP experiments. The identification of 5-HT1B receptors in a tissue derived from the opossum kidney suggests that these receptors may be distributed more widely than previously thought, inasmuch as other studies have found them only in neuronal tissues of rodents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1988

Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype.

The affinities of 34 adrenergic antagonists for alpha-2 adrenergic receptors were determined from homogenate radioligand binding studies using [3H]yohimbine and [3H]rauwolscine. It has been suggested that alpha-2 adrenergic receptors can be subdivided into alpha-2A and alpha-2B subtypes. Oxymetazoline is selective for alpha-2A receptors, whereas prazosin is alpha-2B selective. Five different tissues were used, each of which has only one of the two subtypes: human platelet (alpha-2A), HT29 cell line (alpha-2A), human cerebral cortex (alpha-2A), neonatal rat lung (alpha-2B), and NG108-15 cell line (alpha-2B). The drug affinities were highly correlated when alpha-2A tissues were compared with alpha-2A tissues (r = 0.97 to 0.98) or when the two alpha-2B tissues were compared (r = 0.99). By contrast, comparison of an alpha-2A tissue with an alpha-2B tissue resulted in poor correlations (r = 0.77 to -0.87). Three new subtype selective drugs were identified among these drugs on the basis of at least a 10-fold greater affinity for one subtype. All three were selective for the alpha-2B subtype: ARC-239 (100-fold selective), chlorpromazine (18-fold selective), and 7-hydroxychlorpromazine (17-fold selective). These studies, by demonstrating distinct pharmacological profiles for the two alpha-2 adrenergic receptor subtypes in several different tissues, further support the existence and definition of these subtypes. The identification of a cell line for each subtype should be useful in the further study of alpha-2 adrenergic receptor subtypes.

Animals↗
PubMed1988

Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line.

The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating alpha 2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205,930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Characterization of alpha-2 adrenergic receptors in the OK cell, an opossum kidney cell line.

We have characterized alpha-2 adrenergic receptors in OK cells, an opossum kidney-derived cell line. In membrane saturation binding experiments, [3H]rauwolscine (Kd = 74 pM) was 3-fold more potent than [3H]yohimbine (Kd = 230 pM). Each labeled a single class of binding sites with densities of 135 and 124 fmol/mg of protein for [3H]rauwolscine and [3H]yohimbine, respectively. Inhibition of [3H]rauwolscine and [3H]yohimbine binding by several alpha adrenergic agonists and antagonists demonstrated the radioligands labeled an alpha-2 type adrenergic receptor with a pharmacological profile similar to the alpha-2B receptor subtype. The rank order of potency for antagonist inhibition of binding was yohimbine greater than prazosin = phentolamine greater than chlorpromazine = corynanthine, whereas the rank order of agonist potency was oxymetazoline = clonidine greater than or equal to UK-14,304 greater than or equal to (-)-epinephrine greater than (-)-norepinephrine. The oxymetazoline, clonidine and antagonist inhibition curves were routinely monophasic and modeled best as a single class of binding sites. For the other agonists, inhibition binding curves were biphasic with approximately 35% of the binding sites existing in a high affinity state. These curves were shifted to the right in the presence of 0.1 mM GTP, and in general modeled as a single class of binding sites. UK-14,304, (-)-epinephrine, (-)-norepinephrine and oxymetazoline attenuated parathyroid hormone-stimulated cyclic AMP production by up to 70% in whole cell monolayers in a dose-dependent manner via a pertussis toxin-sensitive mechanism. With the exception of oxymetazoline, this inhibition could be reversed with alpha adrenergic antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1986

Lifestyle modification with heavy alcohol drinkers: effects of aerobic exercise and meditation.

To assess the effects of exercise and meditation on alcohol consumption in social drinkers, 60 male students, between the ages of 21 and 30, all classified as heavy social drinkers, were randomly assigned to one of three conditions: exercise (running), meditation, and a no-treatment control group. The study consisted of three distinct phases: pretreatment baseline (2 weeks), treatment intervention (8 weeks), and a follow-up period (6 weeks). Subjects in the running and meditation conditions met as a group during the treatment intervention phase, and all subjects self-monitored their daily consumption of alcohol throughout the study. The results showed that subjects in the exercise condition significantly reduced their alcohol consumption compared to the no-treatment control condition. The implications of these findings for treatment intervention, and the importance of subject compliance are discussed.

Adult↗
PubMed1984

Carotid sinus hypersensitivity: beneficial effects of dual-chamber pacing.

Three types of carotid sinus (CS) syndrome have been described: cardioinhibitory, vasodepressor and mixed. For the treatment of symptomatic patients with associated significant cardioinhibition, permanent ventricular demand pacing systems are often implanted. Even with this pacing modality, some patients remain symptomatic because of continued (and at times aggravated) vasodepression. This study assesses the effects of loss of atrial preloading and orthostasis after carotid massage in patients with CS hypersensitivity. Eleven patients were studied using constant intra-arterial pressure measurements during either ventricular (VVI) or atrioventricular sequential (DVI) pacing in both supine or upright positions. The measurements performed included the magnitude of decrease in arterial blood pressure (BP), the rate of decrease of BP and the percent change in BP from baseline values. After carotid massage, all 11 patients had greater hemodynamic change with the VVI than DVI pacing mode, whether in the supine or upright position. The decreases in systolic BP were: DVI (supine) 29 mm Hg, VVI (supine) 48 mm Hg, DVI (upright) 37 mm Hg, and VVI (upright) 59 mm Hg (mean group values, p less than 0.001). The rates of decrease of systolic BP were: DVI (supine) 2.9 mm Hg/s, VVI (supine) 5.7 mm Hg/s, DVI (upright) 4.1 mm Hg/s, and VVI (upright) 8.3 mm Hg/s (mean group values, p less than 0.001). VVI pacing, particularly in the upright position, resulted in a significant increase in the incidence of patient symptoms (p = 0.03). Thus, in CS hypersensitivity, VVI pacing results in significant hemodynamic deterioration compared to DVI mode. This aggravation of the vasodepressor component results in increased patient symptoms, and therefore, DVI is the optimal pacing mode.

Adult↗
PubMed1984

Difficulty of extraction of chronically implanted tined ventricular endocardial leads.

The dislodgment rate of permanent pacing ventricular and atrial endocardial leads has significantly decreased with the incorporation of tines as a fixation device. In contrast, transvenous manual extraction of chronically implanted endocardial leads is, at times, clinically indicated, particularly when pacemaker system infection is present. The success rate of such extraction attempts for ventricular endocardial leads over the past 5 years was reviewed. Extraction was usually successful (six of seven attempts) in patients with silicone rubber nontined (or short-tined) older ventricular endocardial leads (Group A). However, in patients with newer urethane long-tined ventricular endocardial leads (Group B), extraction was unsuccessful in three of four attempts. Because of entrapment of the distal electrode tip in the right ventricular apex, manual traction of these leads resulted in permanent conductor material stretching with resultant urethane insulator material breakage in the region of the joints with proximal and distal electrodes. The one successful extraction in Group B was technically difficult and appeared to create a significant risk of intracardiac lead separation. This experience indicates that with improved pacemaker lead design decreased lead dislodgment has been obtained at the cost of increased difficulty of ventricular endocardial lead extraction. Such difficulty should be anticipated when a clinical decision is made to attempt to extract the new urethane long-tined ventricular leads.

Adult↗
PubMed1984

Content and response-style in the construct validation of self-report inventories: a canonical analysis.

A common problem in establishing the construct validity of self-report inventories is the confounding of the purported meaning of test scores with response styles such as social desirability. Partial correlation is a traditional method of controlling such confounding effects. This paper demonstrates the analytic and interpretive advantages of using canonical correlation to remove the effects of a confounding variable. To this end, the present study examined the test protocols of 64 male inpatient alcoholics to determine whether a general measure of mental health (Sulliman Scale of Social Interest) was related to inventories that assess psychopathology (MMPI and PSI) beyond what one could expect by Ss responding in a socially desirable manner. The results of partial correlation and canonical correlation analysis were contrasted, which demonstrated the spuriousness of partial correlations in controlling for social desirability.

Adult↗
PubMed1982

Certification of lead concentration in standard reference materials by isotope dilution mass spectrometry.

In response to needs for analytical standards by researchers studying the exposure of humans to lead, a wide variety of environmental and "food" Standard Reference Materials have been prepared and certified for lead as well as for many other elements. Among the food types are SRM 1571, Orchard Leaves, 45 ppm; SRM 1575, Pine Needles, 10.8 ppm; SRM 1573, Tomato Leaves, 6.3 ppm; SRM 1566, Oyster Tissue, 0.48 ppm; SRM 1577, Bovine Liver, 0.34 ppm; SRM 1568, Rice Flour, 0.045 ppm; and SRM 1567, Wheat Flour, 0.020 ppm. These materials, intended for use in calibrating instruments and methods, have been certified by a definitive method, isotope dilution mass spectrometry. The advantages and disadvantages of this technique are discussed and some suggestions for the use of its isotopic selectivity in the study of lead in the human environment are presented.

Environmental Pollutants↗