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Biomedical subjects

J D Barchas

Publications and source records attributed to J D Barchas.

At least 145 records · Page 8Linked to original sources

Neuroendocrine and neurochemical measurements in depression.

The authors performed dexamethasone suppression tests (DST), TRH infusions, 72-hour urine collections, and lumbar punctures on a group of male depressed patients. Approximately 60% of the patients were DST positive and 33% had a blunted TSH response. Two biologic variables, the 8 a.m. postdexamethasone cortisol and the postprobenecid CSF 5-hydroxyindoleacetic acid (5-HIAA), accounted for over half of the variance in the behavioral measure, the Hamilton score. Plasma cortisol elevation was associated with high 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion; TSH blunting was associated with low urinary MHPG excretion. Comprehensive biologic measures showed certain significant interrelationships and correlations with the severity of depression.

Adult↗

The effects of naloxone in chronic schizophrenia.

In a placebo-controlled, double-blind crossover study of 14 male chronic schizophrenic patients, high doses of the opiate antagonist naloxone were given intravenously. Hallucinations measured on a verbal-report scale were significantly decreased after naloxone administration. The authors suggest that this apparent action of naloxone is mediated by central opiate receptors and that it may result from an interaction between central endorphin systems and central catecholaminergic neurons.

Adult↗

Tyrosine hydroxylase: studies on the phosphorylation of a purified preparation of the brain enzyme by the cyclic AMP-dependent protein kinase.

Tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2](TH) was purified from bovine corpus striatum. The purification involved sequential DEAE cellulose, hydroxylapatite and CM Sephadex C-50 chromatography, followed by glycerol density gradient centrifugation. Final preparations appeared to be 90 to 100% pure as judged by polyacrylamide gel electrophoresis under denaturing conditions in acetic acid-urea. The enzyme was estimated to have a minimum molecular weight of approximately 60,000 daltons. Purified TH could be activated in vitro by incubation with magnesium adenosine triphosphate and the catalytic subunit of cyclic AMP-dependent protein kinase (ATP/protein phosphotransferase; EC 2.7.1.37). When the final purified preparation of TH was incubated under these conditions utilizing [gamma-32P]ATP, it was found to incorporate 0.7 to 0.9 mol of phosphorus/mol of protein. These results suggest that the activation of TH in the presence of phosphorylating conditions is due to its phosphorylation by cyclic AMP-dependent protein kinase.

Animals↗

Clinical application of the probenecid test for measurement of monoamine turnover in the CNS.

The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.

Brain↗

A primate analogue of amphetamine-induced behaviors in humans.

The effects of amphetamine on individual and social behaviors were studied in two colonies of rhesus monkeys. After an initial base-line period, each animal, in turn, received low chronic drug administration for 3 weeks. Between each drug period new base-line data were collected. During amphetamine administration, there was a significant increase in the following behaviors: time spent in "sit tense" postures, frequency of orienting, and frequency of agonistic behaviors. In addition, significant changes were seen in the time spent in proximity with other members of the group. The results are discussed both in terms of across-animal changes as well as with regard to social factors, rank in the hierarchy, and affiliative relationships.

Agonistic Behavior↗

Changes in rat hypothalamic and brain stem catecholamine concentrations following acute administration of phenylethanolamine-N-methyltransferase inhibitors.

The effect of acute phenylethanolamine-N-methyltransferase (PNMT) inhibition on rat brain catecholamine concentrations was studied. All PNMT inhibitors tested were effective in depleting hypothalamic and brain stem epinephrine. Norepinephrine concentrations were unaffected; however, dopamine levels were increased in all areas studied. While several possible explanations are offered for this phenomenon, the mechanism is not yet understood.

Animals↗

Binding of 3H-beta-endorphin to rat brain membranes: characterization of opiate properties and interaction with ACTH.

The binding of tritiated beta-endorphin (3H-beta-EP) to brain homogenates is described. This has been difficult to achieve due to the lack of availability of 3H-beta-EP and to technical difficulties associated with high non-specific binding of beta-EP. We now report that 3H-beta-EP binding is saturable, stereospecific, has high affinity and is inhibited by sodium. Its dissociation rate is ten-fold longer than that of naloxone. Its regional distribution exhibits interesting differences from naloxone and enkephalin binding. ACTH1-24 appears to displace it more effectively than it displaces 3H-naloxone. The results are discussed in terms of multiple transmitter systems and the multiple opiate receptor hypothesis.

Adrenocorticotropic Hormone↗

Determination of tryptophan and metabolites in rat brain and pineal tissue by reversed-phase high-performance liquid chromatography with electrochemical detection.

Tryptophan and many of its indole metabolites were separated using reversed-phase high-performance liquid chromatography (HPLC) and determined using electrochemical detection. This was accomplished isocratically using an acetate--citric acid eluent with various amounts of methanol. Brain and pineal tissue was analyzed for several tryptophan metabolites. Tissue preparation required only homogenization in acidic solution and centrifugation prior to application to the HPLC column. Detection limits in the low picogram range were found for those indoles separated.

5-Hydroxytryptophan↗

beta-Endorphin and schizophrenia.

To study the effects of beta-endorphin in chronic schizophrenia, nine male patients participated in a double-blind crossover comparison of a single intravenous 20-mg injection of beta-endorphin and saline. Bolus injection of beta-endorphin from an albumin-coated syringe produced markedly higher plasma concentrations than did slow intravenous infusion from a non-albumin-coated syringe. Beta-endorphin intravenously injected in nine patients produced a statistically significant increase in serum prolactin levels. In one patient, both 10 mg of morphine sulfate and 20 mg of beta-endorphin produced similar increases in the alpha power of the EEG. In eight patients, beta-endorphin administration was associated with a statistically significant but not clinically obvious improvement in schizophrenic symptoms.

Adult↗

Interaction of opiate peptide and noradrenalin systems: light microscopic studies.

In this light microscopic immunocytochemical study beta-Endorphin (beta-END), leu-enkephalin and dopamine-beta hydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for beta-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between beta-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.

Animals↗

Enkephalinase: selective inhibitors and partial characterization.

There are at least two types of enzymes in brain, endopeptidases and aminopeptidases, which metabolize enkephalins. Evidence is presented to suggest that enkephalinase, an endopeptidase cleaving at the Gly-Phe bond, is specific for the endogenous enkephalinergic system. Selective inhibitors are described for each enzyme. These are parachloromercuriphenylsulfonic acid and puromycin in the case of aminopeptidases and various enkephalin fragments in the case of enkephalinase. Some characteristics of the two types of enzymes are described. Enkephalinase has many properties in common with the well-characterized brain angiotensin-converting enzyme. These two enzymes, however, behaved differently when tested for chloride dependence, for activity in several buffers and for susceptibility to specific inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Opiate antagonists and long-term analgesic reaction induced by inescapable shock in rats.

Five experiments examined the influence of opiate antagonists on both the short-term analgesic reaction resulting 30 min after exposure to inescapable shock and the long-term analgesic reaction resulting after reexposure to shock 24 hr after inescapable shock exposure. Experiment 1 showed that the long-term analgesic reaction could be reduced by administration of naltrexone prior to exposure to inescapable tail shock. Experiment 2 showed that the reduction in the long-term analgesic reaction produced by naltrexone was dose-dependent. Experiment 3 showed that the long-term analgesic reaction could also be reduced by administration of naltrexone prior to reexposure to shock. Experiment 4 showed that the long-term analgesic reaction could be reduced by administration of large dose of naloxone prior to reexposure to shock. Experiment 5 showed that the short-term analgesic reaction was reduced by naltrexone administered prior to inescapable shock. Some implications of these results for the biochemical substrates of both learned helplessness and stress-induced analgesia are discussed.

Animals↗

CSF monoamine metabolites in depression and schizophrenia.

The authors report cerebrospinal fluid (CSF) concentrations of five monoamine metabolites before and after probenecid administration in normal subjects and patients with depression and schizophrenia. No differences were found in baseline metabolite concentrations among the three groups. CSF metabolite and CSF probenecid concentrations were significantly correlated in depressed patients for all metabolites, and there was decreased postprobenecid accumulation of homovanillic acid in the CSF of depressed patients compared with schizophrenic patients and with normal subjects. The authors propose a method for correcting for probenecid concentrations. Data from normal subjects should be of value for other investigators using the probenecid technique.

3,4-Dihydroxyphenylacetic Acid↗

Localization and quantitation of lithium in rat tissue following intraperitoneal injections of lithium chloride. II. Brain.

The distribution of lithium in the rat brain following chronic i.p. injections of lithium chloride has been determined by a radiographic dielectric track registration technique. The study indicated significant differences in lithium distribution in various areas of the brain. Consistently high levels were observed in the neocortex and putamen, and low concentrations in the cerebellum and white matter structures such as the corpus callosum and basis pedunculi. Intermediate levels were found in the thalamus, hypothalamus, septal nuclei, dentate gyrus, hippocampus and substantia grisea centralis.

Animals↗

Selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid.

Details are presented of an improved selected ion monitoring assay for the major biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid (CSF). The metabolites and probenecid are simultaneously extracted with ethyl acetate from an acidified aqueous phase, and are simultaneously converted to pentafluoropropionyl esters by reaction with pentafluoropropionic anhydride and pentafluoropropanol. The esters of the metabolites are analyzed following a single injection of the derivatized sample onto the gas chromatographic column, while the ester of probenecid is analyzed following a separate injection onto the gas chromatographic column. Quantitation is achieved using for internal standards dueterated analogues of the metabolites and a chemical analogue of probenecid. Data are presented on the concentration of free and conjugated forms of the metabolites in lumbar CSF taken from healthy volunteers.

Biogenic Amines↗