Search PubMed⌕ Search

Biomedical subjects

J T Coyle

Publications and source records attributed to J T Coyle.

At least 307 records · Page 17Linked to original sources
PubMed1981

Decreased receptor-binding sites for kainic acid in brains of patients with Huntington's disease.

The specific binding of (3H)kainic acid (KA) to high- and low-affinity receptor sites was assayed in postmortem samples from the brains of patients affected with Huntington's disease (HD) and age-matched controls. Treatment of rat brain with conditions that closely mimic the temperature gradient occurring in postmortem human brain only slightly but not significantly decreased receptor binding by 12 hr after death. In HD brains, total specific binding of (3H)KA was reduced in the caudate nucleus by 51%, putamen by 77%, and frontal cortex by 47%. Specific binding to the high-affinity site was virtually undetectable in the caudate nucleus and was reduced by 90% in the putamen from HD brains. No significant alterations in specific binding of (3H)KA were noted in the insular or temporal cortex, hippocampus, or cerebellum. Thus, losses of KA receptor binding were mainly localized to those regions of the HD brain that are most severely affected by neuronal degeneration, and the high-affinity receptor site appeared more affected.

Adult↗
PubMed1980

Phylogenetic distribution of [3H]kainic acid receptor binding sites in neuronal tissue.

The phylogenetic distribution of specific binding sites for kainic acid was determined in 14 species including invertebrates and vertebrates. The highest level of binding was observed in brains of the frog (Xenopus laevis), followed by the spiny dogfish (Heterodontus francisci), the goldfish (Carasius auratus) and the chick (Gallus domesticus). Although significant specific binding was noted in some of the lowest forms tested (e.g. Hydra littoralis), this was not a consistent observation in the invertebrates. In most cases, specific binding to both high and low affinity sites was detected; notable exceptions were the cockroach brain (Periplaneta americana), which had negligible high affinity binding, and the crayfish brain (Procambarus) which had negligible low affinity binding. In the spiny dogfish, the smooth dogfish and the chick, the highest level of binding occurred in cerebellum with less in the forebrain and the least in the medulla; in the mammalian species, the highest level of binding occurred in the forebrain structures with less in the cerebellum and least in the medulla. Eadie plots of the saturation isotherms for [3H]kainic acid revealed similar kinetics of binding for frog whole brain, rat forebrain and human parietal cortex with two apparent populations of binding sites: KD1 = 25--50 nM and KD2 = 3--14 nM. While binding in the spiny dogfish forebrain and human caudate nucleus occurred exclusively at a high affinity component, the cerebella of chick, rat and man exhibited only a low affinity binding site. In the 3 species studied most extensively, frog, rat and man, unlabeled kainic acid was the most potent inhibitor of the specific binding of [3H]-kainic acid. L-Glutamic acid was 20--20-fold less potent than kainic acid, and D-glutamic acid was 4--2500-fold less potent than its L-isomer. Reduction of the isopropylene side chain of kainic acid to form dihydrokainic acid decreased the affinity of the derivative 115--30,000-fold. Hill coefficients derived from these displacement curves were 1.0 for unlabeled kainic acid but approximately 0.5 for L- and D-glutamic acids and dihydrokainic acid, which is compatible with negative cooperativity. In summary, these studies demonstrated a widespread distribution throughout the animal kingdom of specific binding sites for kainic acid in neural tissue; the characteristics of these receptor sites are remarkably similar from primitive vertebrates to man.

Animals↗
PubMed1980

The development of catecholaminergic innervation in chick spinal cord.

This combined biochemical and histofluorescent study of the embryonic chick was designed to investigate the temporal and spatial development of noradrenergic pathways in the spinal cord. The sequence of catecholaminergic innervation was analyzed by measuring the specific uptake of [3H]norepinephrine, the levels of endogenous norepinephrine, and the distribution of catecholamine histofluorescence. Uptake studies showed early axons present in all levels of spinal cord by 10 days incubation with subsequent increases of uptake activity appearing in a rostrocaudal fashion. Endogenous norepinephrine values were low until day 14, at which time transmitter levels began to increase, approaching hatched values on incubation day 17. Morphologic studies demonstrated catecholaminergic terminals first in the intermediate gray matter and later concentrated in the ventral and dorsal horns. These observations were interpreted to indicate that: (1) noradrenergic axons are an early descending supraspinal pathway; (2) arborization of this system occurs in a rostral-caudal sequence; and (3) monoaminergic uptake mechanisms develop prior to and independent of neurotransmitter synthesis and storage. The development of this noradrenergic system parallels alteration in spinal cord physiology and refinements in the motility of the embryo.

Animals↗
PubMed1980

The differential effect of right versus left hemispheric cerebral infarction on catecholamines and behavior in the rat.

Following right middle cerebral artery ligation in rats, there is a 2-3 week period of spontaneous hyperactivity. Concomitant with this hyperactivity catecholamine concentrations decrease in several areas of the brain including both cortical and subcortical regions. In marked contrast, there are no demonstrable effects of left hemispheric infarction on either spontaneous activity or brain catecholamine concentrations. This asymmetry of behavioral and biochemical response to cerebral infarction cannot be attributed to differences in the lesion size produced in either hemisphere. Feeding and drinking are not affected but the asymmetrical effect on activity can be demonstrated in either a home cage running wheel or an open field environment. It is uncertain whether these findings are the result of hemispheric asymmetries in either catecholaminergic or non-catecholaminergic neurons.

Animals↗
PubMed1980

Characterization of specific, high-affinity binding sites for L-[3H]glutamic acid in rat brain membranes.

L-[3H]Glutamic acid binds reversibly to rat brain membranes with high affinity. Specific binding is linear with tissue concentration and has a pH optimum at neutrality. Saturation isotherms reveal anomolous kinetics of specific binding with an high affinity site with a KD of 11 nM and a lower affinity site with a KD of 80 nM; the Scatchard plots intercept at a common bound/free ratio. Hill plots of the complete saturation isotherms have a slope of 1.0. There are marked regional differences in the distribution of binding sites in rat brain: parietal cortex, frontal cortex, hippocampus greater than striatum greater than thalamus greater than cerebellum, pons-medulla and hypothalamus. Except for a small amount of specific binding in heart, other peripheral tissues do not exhibit specific binding of L-[3H]glutamic acid. Several amino acids with neuroexcitatory effects inhibit the specific binding: L-glutamic acid greater than L-aspartic acid and D,L-homocysteic acid greater than D-glutamic acid and L-cysteine sulfinic acid; related amino acids without neuroexcitatory effects do not inhibit specific binding. Reputed antagonists of glutamate-induced neuronal depolarization block specific binding: alpha-aminoadipic acid greater than 2-amino,4-phosphonobutyric acid greater than glutamate diethylester. Prior kainate lesion of the neurons intrinsic to the striatum results in a 45% decrement in specific binding of L-[3H]glutamic acid whereas cortical ablation, which causes degeneration of a cortical-striatal glutamatergic projection and reduces striatal glutamate synaptosomal uptake, does not affect specific binding. These results are compatible with the interpretation that the binding of [3H]glutamic acid occurs at excitatory receptors on neurons.

Animals↗
PubMed1980

Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects.

A simple, sensitive, and specific radioreceptor assay has been developed for the measurement of anticholinergic drugs in human serum. The assay is based on the competitive inhibition by free anticholinergic drugs in a 0.2-mL sample of serum with the specific binding of the potent muscarinic antagonists, tritiated quinuclidinyl benzilate, to solubilized brain muscarinic receptors. Anticholinergic activity could be detected regardless of drug structure and was quantified against atropine standards. Although the serum levels of anticholinergic drugs varied considerably in 35 patients receiving both neuroleptic and anticholinergic drugs, there was a highly significant inverse correlation between the presence of acute extrapyramidal side effects due to neuroleptics and the serum levels of anticholinergics.

Adult↗
PubMed1980

Local and distant neuronal degeneration following intrastriatal injection of kainic acid.

After intrastriatal injection, the neurotoxin, kainic acid, was cleared from the rat forebrain in a biphasic manner with 70% eliminated within 2 hours; by 24 hours after infusion, less than 1% of the kainic acid remained in the forebrain. The kainic acid diffused into adjacent brain structures, achieving mu molar concentrations in several regions ipsilateral to the injected striatum. At various times after intrastriatal injection of 9.3 nmoles of kainic acid, the brain was serially sectioned; the sections were stained for Nissl substance with cresyl violet or for degenerating neurons with the ammoniacal silver method. Neuronal degeneration spread unevenly into contiguous structures from the central sphere in the injected striatum and affected the ipsilateral pyriform cortex and amygdala, the deep layers of the overlying cerebral cortex, and the medial aspects of the bed nucleus of the stria terminalis and of the nucleus accumbens. In half of the rats, the pyriform cortex contralateral to the side of injection also underwent degeneration. A subpopulation of pyramidal cells in layer IV of the lateral neocortex and the CA3-CA4 pyramidal cells in the ipsilateral hippocampus were selectively affected, whereas adjacent neurons remained intact. The distribution of agyrophilic fibers and terminals in subcortical structures was consistent with the degeneration of neurons of origin in the affected striatal and extrastriatal regions. Brain sections stained by the gold sublimate technique from rats perfused 20 days after injection revealed an intense astrocytic response in all areas affected by acute neuronal degeneration. Extrastriatal damage could be markedly reduced by injection of lower doses of kainic acid (2.3 nmoles) with brief anesthesia; under these conditions, however, the subpopulation of large striatal neurons were relatively resistant, as compared to the Golgi II neurons. These studies demonstrate significant and variable neuronal degeneration beyond the primary site of the lesion after intracerebral injection of kainic acid; several factors affect the pattern of degeneration, including the amount of kainic acid injected, its biological activity, its diffusion, duration of anesthesia, and variable sensitivity of neurons. Consequently, care must be exercised in the use of this neurotoxin to determine the extent and selectivity of neuronal damage, particularly with reference to neuronal vulnerability beyond the central sphere of intrinsic neuronal degeneration.

Amygdala↗
PubMed1980

Low neuroleptic serum levels in patients receiving fluphenazine decanoate.

The authors monitored serum levels of fluphenazine in nine patients following injections of fluphenazine decanoate ranging from 10 to 75 mg. Levels were detected by a radioreceptor assay based on the ability of the drug to complete with 3H-spiroperidol for binding to dopamine receptors in rat caudate membranes. Serum levels of fluphenazine were quite stable over a 2- to 3-week period following single intramuscular injections of the decanoate and correlated with injected dose. Following decanoate treatment serum levels of fluphenazine are substantially lower than levels observed for most other neuroleptics administered orally. This raises questions as to how fluphenazine decanoate can exert therapeutic actions.

Administration, Oral↗
PubMed1980

Clinical state and serum neuroleptic levels measured by radioreceptor assay in schizophrenia.

The authors measured serum neuroleptic levels by radioreceptor assay in 30 schizophrenic patients receiving haloperidol, fluphenazine, chlorpromazine, molindone, thiothixene, or trifluoperazine. Neuroleptic levels were significantly correlated with clinical state, monitored by an abbreviated version of the Present State Examination (the mini-PSE). Poor therapeutic responses were associated with serum levels under 50 ng/ml chlorpromazine equivalents. There was no correlation between neuroleptic dosage and mini-PSE score or between neuroleptic dose and serum neuroleptic levels.

Adolescent↗