Search PubMed⌕ Search

Biomedical subjects

J A Oates

Publications and source records attributed to J A Oates.

At least 145 records · Page 8Linked to original sources
PubMed1982

Clinical experience with malignant pheochromocytomas.

In a 30 year period at Vanderbilt University Hospital, the affiliated Nashville General Hospital and the Nashville Veterans Administration Hospital, 64 patients with pheochromocytoma have been observed. In eight of these, the tumor proved to be malignant. Retrospective review of biologic characteristics of pheochromocytomas in this series included clinical, diagnostic imaging, chemical and histopathologic data. Aside from presence of distant metastases, none of these features had predictive value in indicating the biologic malignant nature of the primary tumor. One patient has been cured by radical surgical resection for 16 years. Three others have died with metastatic tumor and three patients are alive with metastatic tumor.

Adolescent↗
PubMed1982

Shock syndrome associated with mastocytosis: pharmacologic reversal of the acute episode and therapeutic prevention of recurrent attacks.

Patients with mastocytosis at times experience spontaneous episodes of severe flushing and vasodilatory shock. Antihistamine therapy has not been found to prevent uniformly the recurrence of such attacks or reverse the hypotension during the acute episode when given intravenously. We previously found marked overproduction of prostaglandin D2 in two patients with mastocytosis. This suggested the possibility that prostaglandin D2 may be an important mediator in addition to histamine in mastocytosis. We have now generalized our initial findings and have found an increased production of prostaglandin D2 ranging from 1.5-to 32.6-fold in eight additional patients with severe episodes of flushing associated with mastocytosis. In one of those patients, the release of prostaglandin D2 was found to increase approximately 81-fold during an attack of flushing. Without exception, chronic combined therapy with antihistamines and the prostaglandin biosynthesis inhibitor, aspirin, has successfully prevented the recurrence of such severe attacks in these patients, further implicating prostaglandin D2 as an important mediator. The immediate treatment of an acute hypotensive episode, however, represents a different therapeutic situation. We recently observed a severe hypotensive episode in a hospitalized patient with mastocytosis being treated with an H1 receptor antagonist alone. The hypotension was found to be refractory to intravenous fluids, dopamine, and antihistamines, but was immediately reversed by intravenous epinephrine. The self-administration of subcutaneous epinephrine during episodes of flushing in other patients has also been found to ameliorate the flushing rapidly. The apparent unique effectiveness of epinephrine in this situation may derive from an ability of epinephrine to inhibit mast-cell mediator release as a result of beta-adrenergic receptor activation.

Aspirin↗
PubMed1981

Oxygenation of arachidonic acid by hepatic microsomes of the rabbit. Mechanism of biosynthesis of two vicinal dihydroxyeicosatrienoic acids.

[1-14C] Arachidonic (eicosatetraenoic) acid was incubated at 37 degrees C for 15 min with rabbit liver microsomes fortified with NADPH (1 mM). The products were purified by high-pressure liquid chromatography (HPLC) and analyzed by gas chromatography-mass spectrometry. Based on polarity on reversed phase HPLC, the metabolites could be divided into three groups. The major metabolites of lowest polarity were 19- and 20-hydroxyarachidonic acid and 19-oxoarachidonic acid. The major metabolites of medium polarity were two diols, 14,15-dihydroxy-5,-8,11-eicosatrienoic acid and 11,12-dihydroxy-5,8,14-eicosatrienoic acid. Microsomal incubation under atmospheric isotopic oxygen led to incorporation of only one 18O molecule in each diol, indicating that the diols could originate from breakdown of 14(15)-oxido-5,8,11-eicosatrienoic acid and 11(12)-oxido-5,8,14-eicosatrienoic acid, respectively. Major metabolites in the most polar group were 14,15,19- and 14,15,20-trihydroxy-5,8,11-eicosatrienoic acid. 11,12,19- and 11,12,20-trihydroxy-5,8,14-eicosatrienoic acid and 11,12-dihydroxy-19-oxo-5,8,-14-eicosatrienonic acid. About 0.5% of exogenous radioactively labelled arachidonic was covalently bound to microsomal proteins. The metabolites and the protein-bound products were formed in considerably smaller amounts by non-fortified microsomes. Carbon monoxide inhibited this pathway of arachidonic acid metabolism, indicating that these reactions might be catalyzed by the cytochrome P-450-linked monooxygenase systems.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Arachidonic acid metabolism in rabbit renal cortex. Formation of two novel dihydroxyeicosatrienoic acids.

[1-14C]Eicosatetraenoic (arachidonic) acid was incubated with a low speed (17,000 X g) rabbit renal cortical supernatant or with a cortical microsomal suspension fortified with NADPH for 15 min at 37 degrees C. The products which were less polar than prostaglandins on reversed phase high performance liquid chromatography were identified by gas chromatography-mass spectrometry. Both the fortified microsomes and the low speed supernatant formed significant amounts of two novel metabolites, 11,12-dihydroxy-5,8,14-eicosatrienoic acid and 14,15-dihydroxy-5,8,11-eicosatrienoic acid. Other identified products were 19- and 20-hydroxyeicosatetraenoic acid, 19-oxoeicosatetraenoic acid, and in the low speed supernatant, eicosatetraen-1,20-dioic acid. The metabolites were not formed in significant amounts by high speed cortical supernatant or by nonfortified cortical microsomes. Carbon monoxide inhibited formation of these compounds, indicating that they may be formed by the cytochrome P-450-linked renal monooxygenase systems.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Novel transformations of arachidonic acid by the rat thyroid in vitro.

The transformation of arachidonic acid by the rat thyroid in vitro has been investigated. At least two metabolites have been partially characterized: they differed from known metabolites of arachidonic acid in terms of retention volume in liquid chromatography, ultraviolet spectrophotometry and pharmacology (formation not inhibited by indomethacin and enhanced by eicosatetraynoic acid). The analysis by chemical ionization mass spectrometry suggested that these metabolites might be diketo-monohydroxy- and monoketo-dihydroxy-compounds. The conversion of arachidonic acid into these compounds was stimulated by ionophore A23187, decreased by the peroxidase inhibitor methimazole and potentiated by iodide, suggesting that this pathway is under the control of Ca2+ and of a peroxidase product.

Animals↗
PubMed1981

Pharmacokinetics of indomethacin in the neonate. Relation of plasma indomethacin levels to response of the ductus arteriosus.

To identify factors affecting the efficacy of indomethacin in closing symptomatic patent ductus arteriosus (PDA), we studied the pharmacokinetics of intravenous indomethacin, 0.2 mg per kilogram of body weight, in 35 premature infants with symptomatic PDA. Most infants responded to indomethacin with ductus constriction. Indomethacin infusions that were ineffective (seven doses in six patients) were associated with significantly faster clearance, a shorter half-life, and lower plasma levels (p less than 0.05). Six infants had later reopening of the ductus. All six received indomethacin in the first postnatal week; they could not be distinguished from infants with permanent closure on the basis of indomethacin kinetics, but they were of low gestational age. There was a 20-fold variation in plasma indomethacin levels 24 hours after a dose. In view of this variation and the relation between plasma levels and ductus constriction, we suggest that measurement of the plasma indomethacin level could be of value in infants with no response to a first dose.

Ductus Arteriosus↗
PubMed1981

Thromboxane A2 in vasotonic angina pectoris: evidence from direct measurements and inhibitor trials.

Thromboxane A2 (TxA2), an arachidonic acid metabolite causing vasoconstriction and platelet aggregation, is a putative mediator of coronary-artery vasospasm. To determine whether platelet-released TxA2 causes coronary arterial vasospasm, we measured plasma thromboxane B2 (TxB2, the inactive hydration product of TxA2) in the radial-artery and coronary-sinus blood of seven patients and performed therapeutic trials of antiplatelet agents in nine. Although coronary-sinus TxB2 levels rose from the base line approximately fivefold with spontaneous ischemia, samples drawn early in ischemia showed no rise over base-line values. Although a 150 mg dose of aspirin reduced urinary dinor-TxB2 levels by over 75 per cent, it had no effect on the course of the chronic recurrent form of angina pectoris due to vasospasm ("vasotonic angina"). Similarly, indomethacin had no effect on the frequency or duration of ischemia. TxA2 is unlikely to cause vasotonic angina, but it may be released during coronary vasospasm.

Adult↗
PubMed1981

alpha-Methylepinephrine, a methyldopa metabolite that binds to alpha-receptors in rat brain.

The presence of phenylethanolamine-N-methyl transferase in those brain-stem nuclei where methyldopa is thought to act suggested to us that methylepinephrine could be an active metabolite of methyldopa. We assessed the potential of methylepinephrine to be an active metabolite by determining its capacity to compete for ligands which bind to alpha-receptors in rat brain. Thus, the abilities of epinephrine, norepinephrine, methyldopa, (+/-)-methylnorepinephrine and (+/-)-methylepinephrine to compete for alpha 1-([3H]WB-4101) and alpha 2-([3H]clonidine) binding sites in rat brain wee compared. Order of potency at each binding site was: [3H]WB-4101 -- (-)epinephrine = (-)-norepinephrine greater than (+/-)-methylnorepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa; [3H]clonidine -- (-)-epinephrine greater than (+/-)-methylnorepinephrine greater than (-)-norepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa. Since it can compete with a specific ligand for alpha 2-receptors, methylepinephrine could be a centrally active metabolite of methyldopa.

Animals↗
PubMed1981

Renovascular hypertension: anatomic and renal function changes during drug therapy.

Serial renal function studies were performed on 41 patients wtih renovascular hypertension (RVH) secondary to atherosclerotic renal artery disease who had been randomly selected for nonoperative management. In 19 patients, serum creatinine levels increased between 25% and 120%. The glomerular filtration rates dropped between 25% and 50% in 12 patients. Fourteen patients (37%) lost more than 10% of renal length. In four patients (12%), a significant stenosis progressed to total occlusion. Seventeen patients (41%) had deterioration of renal function or loss of renal size that led to operation. One patient required removal of a previously reconstructible kidney. Of the 17 patients with deterioration, 15 had acceptable blood pressure (BP) control during the period of nonoperative observation. Progressive deterioration of renal function in nonoperatively treated patients with atherosclerotic renal artery stenosis and RVH is common, and occurs even in the presence of BP control with drugs.

Adult↗
PubMed1981

Iodination of docosahexaenoic acid by lactoperoxidase and thyroid gland in vitro: formation of an lodolactone.

In the presence of iodide, hydrogen peroxide and lactoperoxidase, docosahexaenoic acid (22:6 omega 3) was converted into iodinated compounds. The major product was identified as 5-iodo-4-hydroxy-7, 10, 13, 16, 19-docosapentaenoic acid, gamma-lactone, on the basis of 125 I incorporation, mass spectrometry, chemical modifications and proton nuclear magnetic resonance spectroscopy. Iodolactonization of docosahexaenoic acid occurred in the rat thyroid in vitro and was inhibited by the peroxidase inhibit or methimazole. These data indicate that formation of an idolactone constitutes one pathway of docosahexaenoic acid metabolism which could be expressed in tissues containing an iodide peroxidase.

Animals↗
PubMed1981

Rabbit renal cortical microsomes metabolize arachidonic acid to trihydroxyeicosatrienoic acids.

(1-14C) Eicosatetraenoic (Arachidonic) acid was incubated with microsomes from rabbit renal cortex and NADPH (1 mM) for 15 min at 37 degrees C. The products were extracted and purified by high pressure liquid chromatography. Some of the most polar metabolites were identified by gas chromatography mass spectrometry. They were 11,12,19- and 11,12,20-trihydroxy-5,8,14-eicosatrienoic acid, 14,15,19- and 14,15,20-trihydroxy-5,8,11-eicosatrienoic acid, and 11,12-dihydroxy-19-oxo-5,8,14-eicosatrienoic acid. These products were likely formed by omega-and ( omega-1)-hydroxylation of 11,12-dihydroxy-5,8,14-eicosatrienoic acid and 14,15-dihydroxy-5,8,11-eicosatrienoic acid, two recently identified metabolites of arachidonic acid in fortified rabbit kidney microsomes.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Stimulus-specificity of the chemotactic deactivation of human neutrophils by lipoxygenase products of arachidonic acid.

Preincubation of human neutrophils with chemotactic concentrations of 5(S)-hydroxy-eicosatetraenoic acid (5-HETE) or 5(S), 12(R)-dihydroxy-6,14 cis-8,10 trans-eicosatetraenoic acid (leukotriene B4) induces a state of preferential chemotactic unresponsiveness to the homologous factor, termed deactivation, and less suppression of the responses to other chemotactic stimuli. The ratio of the concentrations required for maximal chemotactic deactivation of neutrophils to that which stimulates chemotaxis optimally is greater for 5-HETE and leukotriene B4 than for peptide and protein factors. In contrast to other chemotactic factors, 5-hydroperoxy-eicosatetraenoic acid (5-OOHETE) induces neutrophil chemotactic deactivation that is independent of the nature of the subsequent stimulus and is more slowly reversible after elimination of the fluid-phase deactivating factor. The unique characteristics of the chemotactic deactivation of human neutrophils by 5-OOHETE may be attributable in part to its endogenous metabolism to potent deactivating factors or to covalent derivatization of subcellular structures of the neutrophils by the highly reactive 5-OOHETE.

Arachidonic Acid↗
PubMed1981

Prostaglandins and renin release: III. Effects of PGE1, E2 F2 alpha and D2 on renin release from rabbit renal cortical slices.

We have investigated the direct effects of prostaglandins E1, E2, F2 alpha and D2 on renin release from rabbit renal cortical slices. Prostaglandin E1 (PGE1) was the most potent stimulant of renin release, while PGE2 was 20-30 fold less active. PGF2 alpha was found not to be an inhibitor of renin release as reported by others, but rather a weak agonist. PGD2 up to a concentration of 10 microgram/ml had no activity in this system. That the stimulation of renin release by PGE1 is a direct effect is supported by the finding that PGE1-induced release is not blocked by L-propranolol or by delta 5,8,11,14-eicosatetraynoic acid (ETYA), a prostaglandin synthesis inhibitor. The fatty acid precursor of PGE1, delta 8,11,14-eicosatrienoic acid, also stimulated renin release, an effect which was blocked by ETYA. In addition to the above findings, ethanol, a compound frequently used to dissolve prostaglandins, was shown to inhibit renin release.

8,11,14-Eicosatrienoic Acid↗