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T A Hare

Publications and source records attributed to T A Hare.

At least 37 records · Page 2Linked to original sources
PubMed1985

Free and conjugated amino acids in human CSF: influence of age and sex.

An extended baseline characterization of amino acids (AAs) and related amino compounds in CSF is reported. Thirty-one amino compounds were measured in deproteinized CSF before and after acid hydrolysis using a triple-column HPLC/fluorometric analyzer. CSF specimens were collected under strictly controlled conditions from neurologically normal myelogram patients and carefully pooled with regard to subject age and sex. Consideration was given to factors which may produce artifactual alterations in AA levels during CSF collection, storage and handling. Conjugated AAs were determined as the difference between levels of free AAs (measured in CSF prior to hydrolysis) and total AAs (measured in hydrolyzed CSF) and are taken as an index of total CSF peptide AAs. Results documented conjugated forms of all non-acid-labile CSF AAs except citrulline and ethanolamine. In general, ratios of conjugated to free AAs were relatively low, however for the neurotransmitter AAs aspartate, glutamate, glycine and GABA as well as for beta-alanine hydrolysis produced marked increases indicating that these compounds are present predominantly in bound form in CSF. Results also revealed the significant influence of both age and sex on levels of a number of CSF free and conjugated AAs. Compared to younger individuals (those less than 40 years of age), older individuals exhibited significantly higher levels of free aspartate, glycine, alpha-aminobutyric acid, valine, isoleucine, leucine, phenylalanine and 3-methylhistidine as well as significantly lower levels of free phosphoethanolamine, serine, GABA, homocarnosine, conjugated GABA and conjugated beta-alanine. Additionally, significantly higher levels of free tyrosine, ethanolamine, arginine and conjugated aspartate were documented in males compared to females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Rat plasma levels of amino acids and related compounds during stress.

Forty-one amino acids and related compounds were measured (using an HPLC physiological amino acid analysis procedure fully validated for plasma studies) in rat plasma obtained through an indwelling jugular catheter before, during and following a 30 min period of immobilization. Taurine, phosphoethanolamine, aspartic acid, glutamic acid, alanine, cystine, tyrosine, beta-alanine and ethanolamine were increased during the period of stress; whereas, valine, tryptophan and arginine were decreased. Most of these alterations were restored toward normal during the 30 min of rest following the stress period. However, cystine, ethanolamine and beta-alanine remained significantly elevated, and valine, tryptophan and arginine remained significantly reduced. Serine, isoleucine, leucine and glutamine were not significantly altered during the stress period, but became significantly reduced during the 30 min following the stress period. While the patterns of amino acid alterations were generally consistent from animal to animal, the magnitude of the responses were variable with some rats demonstrating much larger responses than others. These results may implicate amino acids as important markers for stress related pathologies. The individual differences noticed may explain why some individuals show more stress effects than others.

Amino Acids↗
PubMed1984

Triple-column ion-exchange physiological amino acid analysis with fluorescent detection: baseline characterization of human cerebrospinal fluid.

A highly resolving triple-column amino acid analyzer with fluorometric detection is described. The reliability of this technique was evaluated and it was used in a baseline investigation of amino acids and related compounds in human cerebrospinal fluid (CSF). The procedure employs three distinct ion-exchange columns to elute the acidic, neutral, and basic amino acids, respectively. Each column is run isocratically with lithium citrate buffers designed to provide overlapping elution profiles. Studies using CSF collected under strictly controlled conditions documented nanomolar concentrations of aspartate, gamma-aminobutyric acid (GABA), beta-alanine, 1-methylhistidine, and 3-methylhistidine, as well as low levels of glutamate, methyllysine, and ammonia. In addition, other common amino acids were also quantified. Chromatograms of CSF from all three systems (acidic, neutral, and basic) exhibited numerous uncharacterized compounds emphasizing the resolution and sensitivity of the analytical procedure. In vitro stability studies revealed that levels of aspartate, glutamate, GABA, homocarnosine, and ammonia are subject to significant change when CSF is maintained at room temperature for various periods of time up to 24 h. It is concluded that the valid and accurate measurement of CSF amino compounds, especially the neurotransmitter amino acids, requires a highly specific and sensitive assay procedure as well as strict control of CSF manipulation in vitro.

Amino Acids↗
PubMed1984

Single unit responses of substantia nigra pars reticulata neurons to apomorphine: effects of striatal lesions and anesthesia.

Many of the behavioral consequences of dopamine system activation are thought to be mediated by substantia nigra pars reticulata output pathways. Extracellular, single unit recording studies were conducted to determine how i.v. administration of the dopamine agonist, apomorphine, affects the activity of these pars reticulata neurons. Results revealed that a 320 micrograms/kg dose of the drug, considered sufficient to stimulate striatal postsynaptic dopamine receptors, caused highly variable changes in reticulata cell firing. Cells exhibited increases, decreases, or no changes in firing. Many cells also displayed marked minute to minute changes in firing. This non-uniform pattern of responses was not related to state of consciousness since similar responses were observed in both chloral hydrate-anesthetized as well as conscious, paralyzed rats. Both the increases and decreases could be reversed by subsequent administration of haloperidol. The variable responses to apomorphine were reduced but not totally prevented by striatal kainic acid lesions, suggesting that changes in striatonigral transmission may account for some but not all of the firing changes which were observed. A lower dose of apomorphine (20 micrograms/kg), thought to act primarily at dopamine cell autoreceptors, had little effect on reticulata cell firing and did not modify the variable responses normally observed after the higher dose. These results contrast strikingly with the consistent excitatory responses to apomorphine which have previously been observed in the globus pallidus and suggest that complex or multiple indirect effects of the drug may contribute to the varied reticulata responses.

Anesthesia, General↗
PubMed1984

Comparison of amino acid levels in rat blood obtained by catheterization and decapitation.

A novel, sensitive and highly resolving amino acid analysis procedure was developed and used to compare two methods of obtaining blood from experimental animals. The procedure, utilizing a meter long microbore HPLC column containing spherical cation-exchange resin and fluorescence detection following postcolumn reaction with o-phthaldialdehyde, was shown to reliably measure forty-one primary amine components in rat plasma. Comparison of values from blood obtained by decapitation and by catheterization documented the significant artifactual influence of the decapitation procedure on approximately half of the measured constituents.

Amino Acids↗
PubMed1984

CSF neurochemistry of women with anorexia nervosa and normal women.

CSF tyrosine, tryptophan, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), gamma-aminobutyric acid, choline, and calcium were compared in 33 anorexic and 14 normal women. The only significant difference between groups was a lower tyrosine level in the anorexic patients; their MHPG level was nonsignificantly higher. No significant group differences in body weight or depressive subgroup were found. HVA levels were positively related to body weight, and choline was negatively correlated with anorexia severity. The role of tyrosine requires further research, but these findings do suggest that HVA and choline increase with some recovery measures and MHPG is increased with this illness.

Adolescent↗
PubMed1984

CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls.

A total of 114 subjects (41 depressed, 20 schizophrenic, 15 manic, and 38 normal controls) underwent lumbar puncture and their CSF was analyzed for levels of tyrosine, tryptophan, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), choline, gamma-aminobutyric acid (GABA), and calcium. Results showed that depressed patients, particularly those over 40 years of age, had lower levels of GABA than did controls, and that their level of HVA increased with age, while controls' decreased. Schizophrenic subjects tended to have higher levels of 5-HIAA and manic subjects tended to have higher levels of HVA and MHPG. Age-associated changes were found in HVA, 5-HIAA, MHPG, GABA, and choline concentrations.

Adolescent↗
PubMed1983

Concentrations of gamma-aminobutyric acid and adenosine in the CSF in progressive myoclonus epilepsy without Lafora's bodies.

Progressive myoclonus epilepsy without Lafora's bodies (PME) is a rare inherited disease found predominantly in Finland, where the incidence is one case per 20,000 to 30,000 children. This fatal disease is characterized by normal early development, progressive stimulus-sensitive myoclonus, ataxia, dysarthria, occasional grand mal seizures, and loss of cerebellar Purkinje cells. Concentrations of gamma-aminobutyric acid in the CSF averaged 89 +/- 10 pmole/mL (mean +/- SE) in eight patients with PME, compared with 135 +/- 18 pmole/mL in ten control patients. The concentrations of adenosine (16 pmole/mL v 17 pmole/mL), inosine (560 pmole/mL v 570 pmole/mL) and hypoxanthine (6.2 nmole/mL v 6.1 nmole/mL) were the same in patients with PME and in controls.

Adenosine↗
PubMed1983

Cerebrospinal fluid GABA measurements: basic and clinical considerations.

The valid measurement of GABA concentration in the CSF for studying in vivo alterations of central nervous system GABAergic activity requires that consideration be given to several factors that affect GABA concentration. These factors include in vivo variables such as the caudocranial concentration gradient in CSF, age, sex, precursor intake, medications, and physical activity, as well as in vitro alterations that can occur during collection, storage, preparation of sample, and analysis. The influence of these factors can be minimized with proper methodology.

Aging↗
PubMed1983

Further characterization of in vitro conditions appropriate for GABA determination in human CSF: impact of acid deproteinization and freeze/thaw.

Recently established standardized protocols for collection, handling, and storage of CSF for measurement of gamma-aminobutyric acid (GABA) have proven valuable in the characterization of various CNS disorders. In response to two recent reports which may have an impact on certain widely used protocols, we have, using the confirmed ion-exchange/fluorometric procedure, systematically evaluated the effects of deproteinization with various concentrations of sulfosalicylic acid (SSA) ranging from 0 to 10% (100 mg/ml), as well as the effects of freeze/thaw (F/T) on CSF GABA levels. Results of F/T studies documented that levels are stable to freezing and thawing. Acid deproteinization studies revealed the presence of an equilibrium between strictly free GABA, demonstrable only in acid-free CSF, and a very loosely bound form of GABA, fully demonstrable only in CSF deproteinized with concentrations of SSA above 1% (10 mg/ml). The relationship between GABA concentrations in undeproteinized and acid-deproteinized CSF revealed a highly significant (p less than .001) correlation, suggesting that alterations of central GABAergic activity would be reflected by either the level of strictly free GABA or free plus loosely bound GABA. This hypothesis was upheld in studies of patients with Parkinson's disease (PD) and Huntington's disease (HD), two neurologic disorders in which dysfunctions of the GABA system have been implicated. Results indicated that CSF GABA levels are significantly reduced in both PD and HD patients compared with neurologically normal controls, whether the measurement is of free GABA or free plus loosely bound GABA. Thus, we conclude that the level of strictly free GABA is stable to freezing and thawing and can only be accurately determined in nonacidified CSF; however, existing protocols employing deproteinization in 5% SSA yield data that provide an equally good reflection of central GABAergic transmission.

Adult↗
PubMed1983

THIP treatment of Huntington's disease.

We evaluated the therapeutic efficacy of gamma aminobutyric acid (GABA) system stimulation in four patients with classical Huntington's disease and one with the hypokinetic-rigid form. Orally administered THIP (4,5,6,7-tetrahydroisoxazolo-[5,4,-c] pyridin-3-ol), a novel GABA receptor agonist, failed to improve motor or cognitive function during a 2-week trial. At maximum levels, THIP mimicked another putative GABA agonist, muscimol, in causing unsteadiness of gait, diminished attention to sensory stimuli, and somnolence. These effects suggest that central GABA systems participate in the regulation of some human and behavioral functions. CSF content of homovanillic acid, a major metabolite of dopamine, increased during high-dose THIP therapy, suggesting that augmentation of dopaminergic function may have contributed to the drug's lack of efficacy.

Adult↗
PubMed1983

Reduced plasma and CSF gamma-aminobutyric acid in affective illness: effect of lithium carbonate.

Plasma and CSF gamma-aminobutyric acid (GABA) levels were determined in patients with affective illness and normal volunteers. Plasma GABA was significantly lower in the medication-free euthymic bipolar group (n = 23, p = 0.03) compared to normal volunteers (n = 36). Lithium-treated euthymic bipolar patients (n = 26) tended to have higher plasma GABA levels (p = 0.09) than the medication-free euthymic bipolar group. Plasma GABA in nine patients, measured in the euthymic state on and off lithium, was higher during lithium treatment (p less than 0.02). In CSF, GABA was found to be significantly lower in a group of euthymic medication-free unipolar and bipolar patients (n = 9) compared to normal volunteers (n = 39, p less than 0.02). CSF GABA, on and off lithium in four bipolar patients, was significantly higher during lithium treatment (p less than 0.02). This effect of lithium, increasing CSF and plasma GABA, may be related to its mechanism of therapeutic action.

Adult↗
PubMed1982

Central nervous system gamma-aminobutyric acid activity in man. Relationship to age and sex as reflected in CSF.

Central nervous system gamma-aminobutyric acid (GABA) activity was demonstrated to be an age- and sex-dependent phenomenon through the study of GABA concentration in lumbar CSF obtained from 87 drug-free normal individuals. Evaluation of the data from homogeneous subgroups of this population disclosed that both the propensity of lumbar CSF GABA levels to decrease with age and the magnitude of the rostrocaudal GABA concentration gradient are more pronounced in females, suggesting possible neuroendocrine involvement. Thus, age and sex are important variables that normally influence central GABAergic activity. Patient populations included in clinical investigations must be age- and sex-matched to avoid invalid conclusions biased by these physiologic variations in CSF GABA concentrations.

Adult↗
PubMed1982

CSF levels of gamma-aminobutyric acid in schizophrenia. Low values in recently ill patients.

gamma-Aminobutyric acid (GABA) levels in CSF were not significantly different in 30 drug-free schizophrenic patients and in 39 normal control subjects, because the control subjects were significantly older. Schizophrenic women had significantly lower levels than age-matched normal control women (less than 30 years). The GABA levels increased with duration of illness, number of hospitalizations, and months of hospitalizations, as well as with age. They correlated nonsignificantly with psychosis levels. After short-term pimozide treatment, GABA levels in all patients were raised, albeit nonsignificantly. The date suggest that low GABA levels may be observed only in the early years of the illness, particularly in female schizophrenic patients, and that these levels increase with time and with long-term neuroleptic treatment.

Adult↗
PubMed1981

Clinical implications of enzyme-mediated alterations of gamma-aminobutyric acid content in human CSF.

Pooled samples of lumbar CSF from nine patients with neurologic disorders were aliquoted and subjected to the differential influence of temperature for four hours. The determination of the gamma-amino-butyric acid (GABA) levels in CSF by ion-exchange-fluorometric analysis before and after incubation showed a progressive increase in GABA content of CSF as a function of temperature, reaching a maximum at 50 degrees C. However, no increases in GABA level were noted in CSF incubated at 80 degrees C or 100 degrees C. These in vitro increases in the GABA content of untreated CSF appear to be entirely secondary to enzyme action, subject to individual and temperature variability, and necessitate standardization of clinical CSF protocols.

Enzymes↗