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Biomedical subjects

J R Simon

Publications and source records attributed to J R Simon.

At least 73 records · Page 4Linked to original sources

Neurochemical studies of the nucleus of the solitary tract, dorsal motor nucleus of the vagus and the hypoglossal nucleus in rat: topographical distribution of glutamate uptake, GABA uptake and glutamic acid decarboxylase activity.

The topographical distribution of glutamate uptake, GABA uptake, and GAD activity was studied in caudal, intermediate and rostral areas of the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DMN) and the of the solitary tract (NTS), dorsal motor nucleus of the vagus (DMN) and the hypoglossal nucleus (n.XII). Within the NTS and n.XII, all three neurochemical parameters exhibited increasing activity from caudal to rostral regions. The distribution pattern for glutamate uptake within the DMN was qualitatively similar to the other nuclei studied, whereas GABA uptake and GAD activity were found to be homogeneously distributed within the DMN. The NTS also exhibited a medial-lateral heterogeneity for glutamate and GABA uptake, with the medial aspect of this nucleus containing significantly higher uptake than the lateral aspect.

Afferent Pathways↗

Histidine transport into rat brain synaptosomes.

Histidine transport and metabolism in rat brain synaptosomes were investigated to study the possible role of histidine uptake in the synthesis of the putative neurotransmitter histamine (HA). Histidine uptake was found to be regionally distributed and temperature sensitive, and was not totally independent of sodium or potassium ions. Transport was inhibited by metabolic inhibitors, as well as by promethazine and quinacrine. A number of other HA-related agents and several histidine metabolites had no effect. Kinetic analyses of histidine transport revealed the presence of both high- and low-affinity systems in cerebral cortex. Histidine uptake increased following preexposure of synaptosomes to depolarizing concentrations of potassium. This effect was dependent on the presence of calcium ions during the preincubation. No newly formed [3H]HA was detectable in rat brain synaptosomes following [3H]histidine transport. Lesions of the medial forebrain bundle did not alter histidine uptake in the hippocampus or cerebral cortex. Ontogenic studies indicated that the histidine uptake system developed rapidly and reached a peak during postnatal days 12-17. Overall, the present findings do not support a role for histidine transport in the regulation or maintenance of neurotransmitter pools of HA in rat brain.

Animals↗

Reaction time to word meaning and ink color of laterally-presented stroop stimuli: effects of handedness and sex.

In two experiments, subjects pressed a key labeled Red or Green in response to a 100 msec duration stimulus presented to the left or right visual field. In Experiment I, subjects responded to the meaning of Stroop words; the stimulus was the word Red or Green printed in red, green, or white ink. In Experiment II, subjects responded to ink color; the stimulus was either the word Red or Green printed in red or green ink or a red or green color patch. In each experiment, there were 20 strongly right-handed subjects and 20 strongly left-handed subjects. Half the subjects in each handedness group were male and half were female. In both experiments, RT was faster when words were presented to the right visual field than to the left visual field, suggesting that both meaning and ink color of Stroop words were processed more quickly in the left hemisphere. Results of both experiments revealed faster reactions when meaning and ink color of the Stroop words were congruent than when they were not. A comparison with baseline trials indicated that the RT difference between responses to congruent and incongruent Stroop words was due to the incongruent cue interfering with information processing rather than to the congruent cue facilitating processing. Hypothesized interactions between stimulus position, congruence, handedness and sex were not significant.

Adolescent↗

Cardiovascular effects of 3-mercaptopropionic acid and levels of GABA in regions of the brain of guinea-pigs.

3-Mercaptopropionic acid (3-MP), an inhibitor of the synthesis of gamma-aminobutyric acid (GABA), was administered to anesthetized rats and guinea-pigs in order to examine the relationship between the effect of this agent on regional levels of GABA in the brain and cardiovascular function. After a latent period, 3-mercaptopropionic acid (0.16 ml/kg, i.p.) produced initial increases in blood pressure and heart rate in rats followed by vagal bradycardia and hypotension. Guinea-pigs treated with 3-mercaptopropionic acid developed one of three patterns of cardiovascular changes. The type I response consisted of a period of sympathetically-mediated hypertension and tachycardia followed by vagal bradycardia. Type II animals exhibited increased arterial pressure and heart rate, but no vagal activation. Type III and control animals exhibited no significant cardiovascular changes following administration of 3-mercaptopropionic acid or appropriate vehicle. Regional levels of GABA in brain, measured at 90 min after treatment were significantly lower than control in type I and II animals in 3 of 4 areas of the brain measured, but not in type III guinea-pigs. When decreases in levels of GABA were compared to the changes in cardiovascular parameters for individual animals, the decrease in heart rate at the time of sacrifice was directly correlated with the decrease in medullary levels of GABA in type I animals. Conversely, in type II guinea-pigs, decreases in hypothalamic levels of GABA correlated inversely with heart rate at sacrifice. These results suggest that activation of cardiac sympathetic and parasympathetic nervous pathways following the administration of 3-mercaptopropionic acid may result from decreased levels of GABA in different regions of the brain.

3-Mercaptopropionic Acid↗

Antibacterially active substituted anilides of carboxylic and sulfonic acids.

Anilides of carboxylic and sulfonic acids were prepared and tested for antimicrobial activity. While these anilides were ineffective against Gram-negative organisms, there was a good correlation between chemical structure and biological activity against Gram-positive species. Both the nature and position of the benzene ring substituents and the length of the carbon side chain affected the activity and specificity of the compounds. The highest activity was observed when the acyl or sulfuryl moiety had a C7-C9 side chain attached. The CONH and SO2NH bridging groups were equally effective. The attachment of COOH or COOCH3 groups in the omega-position did not effect activity, but the substitution of the acidic proton of the sulfonamide group by an alkyl group rendered the compound inactive. Six compounds, which were substituted anilides of sulfonic acids, fatty acids, or the analagous alpha-methylene-substituted acids, were bacteriostatic at 10 ppm against Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis, and Lactobacillus plantarum. One of these compounds, 2-hydroxy-5-nitroanilide of alpha-methylenedecanoic acid, was bactericidal at 1 ppm.

Anilides↗

Common induction and regulation of biphenyl, xylene/toluene, and salicylate catabolism in Pseudomonas paucimobilis.

A strain of Pseudomonas paucimobilis (strain Q1) capable of utilizing biphenyl was isolated from soil. This strain grew not only on substituted biphenyls, but also on salicylate, xylene or toluene or both (xylene/toluene), and substituted benzoates. Evidence is presented that the catabolism of biphenyl, xylene/toluene, and salicylate is regulated by a common unit in this strain. The catabolism of biphenyl, xylene/toluene, and salicylate is interrelated, since benzoate and toluate are common metabolic intermediates of biphenyl and xylene/toluene, and salicylate is produced from 2-hydroxybiphenyl (o-phenylphenol). All the oxidative enzymes of the biphenyl, xylene/toluene, and salicylate degradative pathways were induced when the cells were grown on either biphenyl, xylene/toluene or salicylate. The P. paucimobilis Q1 cells showed induction of the meta-cleavage enzymes of both 2,3-dihydroxybiphenyl and catechol. Biphenyl-negative derivatives of strain Q1 were simultaneously rendered xylene/toluene and salicylate negative, whereas reversion to the biphenyl-positive character of such derivatives invariably led to a xylene/toluene- and salicylate-positive phenotype. Growth of the P. paucimobilis Q1 cells with benzoate as a sole carbon source allowed the induction of only the ortho pathway enzymes, suggesting that biphenyl, xylene/toluene, or salicylate specifically induced the meta pathway enzymes for the oxidative degradation of these compounds.

Alcohol Oxidoreductases↗

Cortical modulation of cholinergic neurons in the striatum.

Previous reports suggest the existence of a corticostriatal pathway which might use glutamate as the transmitter. In the present study, the possible influence of this pathway on striatal cholinergic neurons was investigated. Two weeks following surgical destruction of the cerebral cortex, the high affinity uptake of glutamate and choline into striatal synaptosomes was significantly reduced whereas GABA uptake was unaffected. In acute experiments (1 hour following decortication), only choline uptake was significantly reduced while the uptake of glutamate and GABA were not altered. Acute injection (2 minutes) of kainic acid into the striatum, 1 hour after decortication, reversed the effect of the decortication on choline uptake, perhaps by simulating an excitatory input to the striatum which was presumably removed by the cortical ablation. These observations are consistent with the existence of a cortical input (perhaps glutamatergic) to the striatum and suggest that striatal cholinergic neurons can be influenced by this cortico-striatal pathway.

Animals↗

High-affinity choline uptake in the hippocampus: its relationship to the physiological state produced by administration of barbiturates and other treatments.

Choline uptake in hippocampal synaptosomes was not inhibited by pentobarbital administration when rats were decapitated immediately upon loss of the righting reflex (3-4 min) even though it was inhibited at later times post-injection, when the rats were still unable to right themselves. Choline uptake was increased when the animals were decapitated at convulsion after an injection of picrotoxin, high doses of bicuculline, or one of the convulsant barbiturates. However, another convulsant barbiturate, as well as strychnine and lower doses of bicuculline, did not increase choline uptake even though the animals also convulsed. Thus loss of righting reflex or convulsion is not directly correlated with changes in choline uptake. At 7 min after injection, levels of pentobarbital in the hippocampus (and other brain regions) were correlated with the degree of inhibition of choline uptake up to about 50% inhibition; however, greater inhibition could not be achieved with much higher brain levels of the drug. Although hippocampal uptake was partially inhibited at 1 h after septal lesions, 3 h after the lesion the inhibition was no longer apparent. Inhibition was almost complete 10-12 days after the lesion. These results suggest that other factors in addition to impulse flow influence choline uptake.

Animals↗

Regional distribution of cholinergic parameters within the rat striatum.

The topographical distribution of choline acetyltransferase, muscarinic receptor binding and high affinity choline uptake was studied in 21 separate areas of the rat striatum. The areas of the nucleus chosen represented dorsolateral, dorsomedial, ventrolateral and ventromedial regions along the rostrocaudal aspect of the striatum, such that a three-dimensional distribution of the cholinergic parameters could be obtained. Within any given rostrocaudal section, no significant dorsoventral differences were noted for any of the cholinergic parameters. On the other hand, marked differences were found in a comparison of the medial and lateral striatum. Choline acetyltransferase, muscarinic receptor binding and high affinity choline uptake were more concentrated in the lateral striatum than the medial striatum, and the magnitude of this medio-lateral disparity increased from rostral to caudal regions of the nucleus. The lateral striatum exhibited no significant rostrocaudal variations in the cholinergic parameters; however, the medial portion of the striatum did exhibit differences along its rostrocaudal extent, with the rostral-most sections being enriched relative to the more caudal sections. These results suggest that the cholinergic system in the striatum is heterogeneously distributed within this nucleus, with the lateral portion possessing a greater cholinergic innervation than the medial portion. They further suggest that future neurochemical studies of cholinergic alterations in the striatum should include a consideration of the possibility of regional effects within the nucleus rather than treating the striatum as a homogeneous tissue.

Animals↗

Distribution of choline acetyltransferase, acetylcholinesterase, muscarinic receptor binding, and choline uptake in discrete areas of the rat medulla oblongata.

Quantitative measurements were made of choline acetyltransferase (CAT) activity, acetylcholinesterase (AChE) activity and cholinergic muscarinic receptor binding ([3H]QNB) in eight areas of a cross-section of the rat medulla oblongata. A fourth cholinergic parameter, high-affinity choline uptake, was measured in three groups of these areas. CAT, AChE and [3H]QNB binding were found to be highest in the hypoglossal nucleus and the dorsal motor nucleus of the vagus; the lowest value was in the area which contains the inferior olive and the corticospinal tract. The distribution of AChE and CAT activities varied approximately 7- to 10-fold among the eight regions examined, whereas that of the muscarinic receptor varied only about 4-fold. The Na+-dependent high-affinity choline uptake varied approximately 20-fold from the region with the lowest activity (inferior olivary nucleus and corticospinal tract) to that with the highest activity (tissue areas containing the dorsal motor nucleus, hypoglossal nucleus of the solitary tract and nucleus cuneatus). The four cholinergic parameters are statistically correlated throughout all the areas of the medulla which were studied.

Acetylcholinesterase↗

Effects of changing compatibility relationships on reaction time to the first stimulus in a double-stimulation task.

This study investigated the effects of manipulating the response requirement to the second stimulus (S2) on reaction time (RT) to the first stimulus (S1) in a double-stimulation choice RT task. Forty subjects responded to the 100 msec presentation of a left or right light by pressing the key on the same or opposite side as the light. Treatment conditions included a single-stimulation control (no S2 presented), and two double-stimulation conditions each requiring two responses (R1 and R2) in close succession, in one of these latter conditions, the rule governing R2 was the same as that governing R1 while, in the other, the rule governing R2 changed. Results showed the typical double-stimulation effect; i.e., increased latency of R1 when it was followed by S2 - R2. More importantly, R1 latency was increased further when the rules governing R1 and R2 were different. Results are discussed in terms of divided preparation capacity as well as other theories of the psychological refractory period.

Journal Article↗

Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system.

Parameters affecting the binding of [3H]glycine to membrane fractions isolated from the cerebral cortex, midbrain, cerebellum, medulla oblongata, and spinal cord of the rat were investigated in a Na+-free medium. A [3H]glycine binding assay was established in which the binding was specific, saturable, pH-sensitive, and reversible. Conditions were chosen in an effort to minimize binding to glycine uptake sites. From data on specific [3H]glycine binding Scatchard plots were prepared and the KD and Bmax values were calculated. Two glycine binding sites (high and low affinity) were identified only in the medulla (KD: 44, 211 nM; Bmax: 361, 1076 fmol/mg protein) and spinal cord (KD: 19, 104 nM; Bmax: 105, 486 fmol/mg protein). The ranges of the KD and Bmax values for the other three areas studied were 59 to 144 nM and 882 to 3401 fmol/mg protein, respectively. When the glycine content of each area, expressed as fmol/neuron, was plotted against the respective KD (high affinity), a negative correlation was found (r = --0.90; p less than 0.05). A similar negative correlation was found between the glycine content and Bmax (r = --0.88; p less than 0.05). Hill plots indicated a slope of essentially 1.0 for all areas. GABA, taurine, strychnine, diazepam, bicuculline, and imipramine had little or no effect on [3H]glycine binding.

Amino Acids↗

Retrieval time in a monaural learning task.

This study examined the possible role of retrieval and/or storage processes in auditory asymmetry phenomena. Subjects pressed a left- or right-hand key labeled "yes" or "no" to indicate whether a monaural tone had just been presented to the ear specified by a left or right probe light. Subjects were faster in indicating that the probed ear had been stimulated than in indicating that it had not been stimulated. Subjects also responded faster when the location of the response key and probe light corresponded than when they did not. The methodological implications of the latter finding for research on hemispheric dominance were discussed. Finally, there was no evidence that retrieval time varied as a function of either the ear probed or the ear stimulated.

Auditory Perception↗