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Biomedical subjects

D L Murphy

Publications and source records attributed to D L Murphy.

At least 307 records · Page 17Linked to original sources
PubMed1986

Erythrocyte Rh antigens increase with red cell age.

Certain blood group antigens may play a role in the removal of senescent red cells from the circulation. In order to elucidate this hypothesis, we have investigated the effect of red cell aging on Rh blood group antigens. Red cells from volunteer donors were separated into subpopulations of uniformly defined densities on discontinuous Stractan density gradients. The number of the five major Rh antigen sites of each fraction was determined both by enzyme-linked immunosorbent assay (ELISA) and by hemagglutination-scoring technique. All Rh antigens tested increased with cell age (p less than 0.01). The data indicate that there is a positive correlation between red cell age and the Rh blood group antigen site number.

Age Factors↗
PubMed1986

Further studies of the putative serotonin agonist, m-chlorophenylpiperazine: evidence for a serotonin receptor mediated mechanism of action in humans.

To further evaluate the effects and mechanism of action of the putative serotonin agonist m-chlorophenylpiperazine (m-CPP) in humans, changes in plasma prolactin, cortisol, growth hormone, ACTH and body temperature were studied in a group of 10 healthy volunteers following oral administration of m-CPP (0.75 mg/kg), before and after pretreatment with the serotonin receptor antagonist metergoline (MTG). M-CPP produced transient significant increases in plasma prolactin, cortisol, ACTH and in body temperature, but did not significantly alter plasma growth hormone concentration. Moreover, pretreatment with the 5HT antagonist metergoline blocked the m-CPP-induced hormonal and temperature changes. These findings provide strong support for m-CPP's effects in humans being mediated through an interaction with 5HT receptors, and thus support the usefulness of m-CPP as a pharmacologic tool for studying disease and drug-induced alterations in serotonin function in man.

Adrenocorticotropic Hormone↗
PubMed1986

Tetrahydrobiopterin administration to rhesus macaques. Its appearance in CSF and effect on neurotransmitter synthesis.

Tetrahydrobiopterin, the hydroxylase cofactor (BH4) was administered (i.v. 20 mg/kg) to Rhesus monkeys. Within 90 min of its administration CSF cofactor levels increased significantly above baseline levels. Peak CSF levels were attained at 90-180 min time period following cofactor injection and returned to baseline gradually over the next 15 hrs. The increased brain cofactor levels had no apparent effect on synthesis of dopamine, norepinephrine or serotonin as evidenced by a lack of change in the levels of the metabolites homovalillic acid, 3-methoxy-4-hydroxyphenyleneglycol, and 5-hydroxyindoleacetic acid. The present results using primates suggest no apparent effect of increased cofactor levels on monoamine biosynthesis. However, it remains to be explored whether monoamine synthesis could be affected by increased cofactor levels in the pathological situation.

Animals↗
PubMed1986

Measurements of n-p correlations in the reaction of relativistic neon with uranium.

We report a preliminary measurement of coincident neutron-proton pairs emitted at 45 degrees in the interaction of 400, 530, and 650 MeV/A neon beams incident on uranium. Charged particles were identified by time of flight and momentum, as determined in a magnetic spectrometer. Neutral particles were detected using a thick plastic scintillator, and their time of flight was measured between an entrance scintillator, triggered by a charged particle, and the neutron detector. The scatter plots and contour plots of neutron momentum vs. proton momentum appear to show a slight correlation ridge above an uncorrelated background. The projections of this plane on the n-p momentum difference axis are essentially flat, showing a one standard deviation enhancement for each of the three beams energies. At each beam energy, the calculated momentum correlation function for the neutron-proton pairs is enhanced near zero neutron-proton momentum difference by approximately one standard deviation over the expected value for no correlation. This enhancement is expected to occur as a consequence of the attractive final state interaction between the neutron and proton (i.e., virtual or "singlet" deuterons). The implications of these measurements are discussed.

Elementary Particles↗
PubMed1986

Smooth pursuit eye movement disorder and its psychobiologic correlates in unmedicated schizophrenics.

The accuracy of smooth pursuit eye movements (SPEMs) was evaluated electrooculographically in 14 medication-free schizophrenics. Concentrations of monoamine metabolites and gamma-amino-butyric acid (GABA) were measured in their cerebrospinal fluid (CSF). Ventricular-brain ratios (VBR) were determined by computed axial tomography (CT scan). Premorbid adjustment was evaluated by the Phillips Scale. The SPEMs of eight of the patients were reevaluated after 2 weeks of treatment with either prazosin or pimozide. No consistent significant correlations were found between SPEM accuracy and CSF metabolite concentrations, VBR, or premorbid adjustment. SPEM accuracy was not correlated with number of days off medication and was significantly correlated when measured before and during medication.

Adult↗
PubMed1986

Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl.

Melatonin was measured in plasma collected between 8:00 and 8:30 a.m. from 27 depressed patients studied before and after 21- to 24-day treatment with three monoamine oxidase (MAO) inhibitors. Baseline plasma melatonin concentrations determined by radioimmunoassay were 4.0 +/- SD 4.7 pg/ml. Tranylcypromine, a nonselective MAO inhibitor given in doses of 20-40 mg/day for 3 weeks, significantly elevated plasma melatonin to 10.6 +/- SD 2.0 pg/ml. Clorgyline, given in doses of 15-30 mg/day for 3 weeks, produced a significant, approximately three-fold increase in plasma melatonin (13.6 +/- SD 13.5 pg/ml). This clorgyline dose was selective for MAO type A inhibition, as MAO-B activity measured in platelets from the same blood samples was unaffected by clorgyline. In contrast, the selective MAO-B inhibitor deprenyl (10-30 mg/day for 3 weeks) led to a 96 +/- 4% inhibition of platelet MAO-B activity but no significant change in plasma melatonin (5.1 +/- SD 4.2 pg/ml). As both serotonin and norepinephrine are preferentially metabolized by MAO-A rather than MAO-B, an increased availability of serotonin (the precursor of melatonin) or enhanced noradrenergic function might mediate the melatonin changes observed to follow MAO-A but not MAO-B inhibition.

Blood Platelets↗
PubMed1986

Indices of noradrenergic output in depression.

Concentrations of plasma norepinephrine (NE) and plasma-3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure, and heart rate were measured on 2 days in 25 depressed patients and 25 controls. Comparisons were made between patients and controls, and also between days for both groups, to determine the short-term stability of these measures. The means of the plasma and urinary noradrenergic metabolite measures were not significantly different between groups. The variance of plasma MHPG, plasma NE, and mean blood pressure was greater in the depressed patients than in controls. Blood pressure, plasma MHPG, and plasma NE were relatively stable as suggested by the significant correlations between the 2 days for each of these variables. Plasma NE, plasma MHPG, and the sum of the deaminated urinary metabolites (MHPG and vanillylmandelic acid) were significantly intercorrelated. These results support other data in suggesting that plasma concentrations of NE and MHPG may be useful measures of noradrenergic activity, but may not consistently distinguish depressed patients from controls.

Adult↗
PubMed1986

Pharmacologic modelling of Alzheimer's disease.

Evidence pointing to the central role of the cholinergic system in normal human memory function and disorders such as Alzheimer's disease has grown tremendously in recent years. Anticholinergic and non-cholinergic agents have been found to create transient memory impairments in young adults which mimic the changes associated with normal aging or amnesia. The rationale for using scopolamine, a centrally active anticholinergic agent, as a pharmacologic probe of memory function is reviewed using data from studies in animals and humans. The cognitive functioning of normal elderly controls given scopolamine is compared to the baseline functioning of patients with Alzheimer's disease, followed by a discussion of the use of scopolamine as a modelling agent for dementia.

Adult↗
PubMed1986

Design and interpretation of opiate antagonist trials in dementia.

In view of the reports of possible beneficial effects of naloxone in dementia, rationales and strategies for studying endogenous opiate systems are reviewed. Important considerations in the design and interpretation of clinical investigations using naloxone are also reviewed. The nature and distribution of endogenous opiate systems are summarized from an historical perspective. Endogenous opiate systems are distributed throughout the central nervous system and play important roles in a variety of brain functions, including memory and learning. In view of this, several rationales are evident for studying endogenous opiate systems in dementia, since it is a syndrome in which structures known to contain opiate systems are disturbed, functions modulated by opiate systems are disturbed, and other neurotransmitter systems (functionally linked to endogenous opiate systems) are disturbed. Different strategies for studying endogenous opiate systems are reviewed, including examination of body fluids and pharmacologic challenge studies. Naloxone hydrochloride, a competitive opiate receptor antagonist, is a commonly used pharmacologic agent. The design of a multidose naloxone study of 12 dementia patients is discussed, with reference to the pharmacokinetics, pharmacodynamics, and specificity of naloxone as well as to the nature of the dependent measures selected for this study. No cognitive benefit was observed in this study. Behavioral arousal was observed at naloxone doses, with more evident psychomotor retardation at higher doses. These findings are contrasted with the results of naloxone challenges in other studies. The varying effects of naloxone within and across populations can be conceptualized in terms of the basic and clinical considerations previously discussed. The importance of dose-finding studies is stressed for this and other drug trials.

Alzheimer Disease↗
PubMed1986

Anti-beta-endorphin immunoglobulin G in humans.

Human IgG specific for beta-endorphin was identified by enzyme-linked immunoabsorbent assay and isolated by affinity chromatography. From a sample of 27 subjects, three individuals with major depression demonstrated plasma IgG highly reactive with human beta-endorphin, while four other subjects (two with depression and two randomly selected blood donors) had intermediate reactivity. The recognition site for beta-endorphin was retained by F(ab')2 fragments.

Adult↗
PubMed1986

Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function.

Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO)-inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin. Chronically-administered tricyclic antidepressants with prominent effects on monoamine uptake and on beta-adrenoceptors reduce pineal and plasma melatonin in rodents; however, in two studies in depressed patients, either no change or a significant elevation in nocturnal plasma melatonin followed 3 to 4 weeks treatment with desipramine. As depressed patients in these and several other recent studies had lower pretreatment nighttime melatonin peaks than controls, these findings may be relevant to the presynaptic and receptor adaptational consequences of chronic antidepressant drug treatment. The significant effects on melatonin of other drugs which affect monoamine function and have psychotropic effects, including lithium, propranolol, amphetamine and several monoamine precursors, together with recent observations of the existence of muscarinic and benzodiazepine receptors in the pineal gland are in accord with previous suggestions that the study of pineal function and melatonin production provides a valuable model system for psychopharmacological investigations.

Animals↗
PubMed1986

Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase.

This is a reversed-phase liquid-chromatographic method, with electrochemical detection, for simultaneously measuring, in plasma, the concentrations of the catecholamine precursor dihydroxyphenylalanine (DOPA); the endogenous catecholamines norepinephrine, epinephrine, and dopamine; and the deaminated catecholamine metabolites dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG). We used this method to assess effects of monoamine oxidase (EC 1.4.3.4) inhibition in humans. Plasma DHPG concentrations as determined by the present method (mean 826, SEM 61 ng/L) were similar to those found by other methods. Inhibition of monoamine oxidase (by administering deprenyl or tranylcypromine) decreased plasma DHPG by greater than 65%, plasma DOPAC by greater than 50%, and plasma DOPA by about 20%, without consistently affecting norepinephrine or epinephrine. Simultaneous measurement of DOPA, catecholamines, and DHPG may be useful for examining the synthesis, release, and intraneuronal metabolism of norepinephrine. The assay method is rapid, reliable, and simple, and it provides a more comprehensive assessment of noradrenergic nervous function than does measurement only of catecholamines.

Alzheimer Disease↗
PubMed1986

Use of serotonergic agents in the clinical assessment of central serotonin function.

To assess the status of the brain serotonergic system in relation to ongoing behavior, agents with predominant actions on serotonin synthesis, release, uptake, and receptor mechanisms are being evaluated. Abnormalities in the neuroendocrine responses to tryptophan, 5-hydroxytryptophan, fenfluramine, and m-chlorophenylpiperazine are under exploration in depressed patients. These agents are also being used to assess postulated changes in serotonin metabolism and serotonin receptor adaptation during longer term treatment with antidepressant drugs, lithium, and other psychoactive agents. Concurrent studies in rodent and nonhuman primate models are helping to validate these approaches to the exploration of the role of serotonin in psychiatric and neurologic disorders.

5-Hydroxytryptophan↗
PubMed1986

Rapid antidepressant effect of addition of lithium to tranylcypromine.

A chronically depressed patient who had not responded to treatment with several tricyclic antidepressants and monoamine oxidase inhibitors alone, responded within hours following the addition of lithium to ongoing tranylcypromine treatment in a double-blind medication trial. The findings are discussed in the context of reports of lithium augmentation of other antidepressants.

Depressive Disorder↗