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Biomedical subjects

J D Connor

Publications and source records attributed to J D Connor.

At least 109 records · Page 6Linked to original sources
PubMed1980

Relative potency of amphetamine isomers in causing the serotonin behavioral syndrome in rats.

High doses of amphetamine evoke a behavioral syndrome in man which is similar to paranoid schizophrenia. The similarities between the behavioral effects of amphetamine and the symptoms of an endogenous behavior disorder suggest a mechanistic relationship between the two states. This study deals with a specific set of behavioral signs in the rat which are caused by relatively high doses of amphetamine and are mediated by serotonin receptor activation. Experiments on the mechanism by which amphetamine evokes this behavioral syndrome reveal that the l-isomer, like the d-isomer, acts indirectly, i.e., by release of endogenous serotonin. Furthermore, when d- and l-isomers are compared on the basis of potency in causing the serotonin behavioral syndrome, the d form is between two and three times more potent than the l-isomer. This result is consistent with the greater potency of the d-isomer (approx 2 to 1) in exacerbating symptoms of paranoid psychosis in humans. The data indicate that the serotonin behavioral syndrome in rats caused by relatively high doses of amphetamine may be the experimental counterpart of the paranoid psychosis induced in man by high doses of amphetamine.

Amphetamine↗
PubMed1979

Effect of morphine on 'wet-dog' shakes caused by cerebroventricular injection of serotonin.

Intraventricular administration of serotonin to rats causes 'wet-dog' shakes, a sign of morphine withdrawal. The frequency of shakes is dose-dependent. Shaking is potentiated by pretreatment with an inhibitor of monoamine oxidase or with 5,7-dihydroxytryptamine, and is depressed by morphine or serotonin receptor blockers. Depression of serotonin-induced shaking by morphine is reversed rapidly by naloxone. However, naloxone did not reverse the inhibition of 'wet-dog' shakes caused by serotonin receptor blockers.

5,7-Dihydroxytryptamine↗
PubMed1978

Simple sensitive microbioassay for adenine arabinoside and hypoxanthine arabinoside in human plasma.

Previous methods using low- or high-pressure liquid chromatography and UV absorbance for quantitation of arabinosides in plasma can practically detect only >/=200 ng of adenine arabinoside and >/=100 ng of hypoxanthine arabinoside per ml, and they require expensive equipment and expert technical assistance. We describe in this report a simple quantitative microbioassay for arabinosides in human plasma based on their ability to inhibit the cytopathic effect of vaccinia virus in an adenosine deaminase-free cell culture system. Using prior separation of nucleosides in plasma by thin-layer chromatography, followed by the microbioassay, we quantitated adenine arabinoside with a sensitivity of approximately 4 ng/ml and hypoxanthine arabinoside at approximately 625 ng/ml. This assay method is simple, sensitive, and reproducible, requires small plasma samples, measures biological activity, and is adaptable to routine use. It is an important tool for evaluating the pharmacology of adenine arabinoside and Ara-AMP in patients in current clinical trials.

Humans↗
PubMed1978

Evidence that serotonin mediates some behavioral effects of amphetamine.

In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.

5,7-Dihydroxytryptamine↗
PubMed1978

Specificity of a rat behavioral model for serotonin receptor activation.

Pharmacological stimulation of central serotonin (5-HT) receptors causes a behavioral syndrome characterized by simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. This syndrome has been proposed and used as a model for 5-HT receptor activity. Questions have been raised about the possible involvement of catecholamines. This study was designed to differentiate behavioral signs contributed by 5-HT from those that might be due to catecholamines. Depletion of catecholamines by alpha-methyl-p-tyrosine, or depletion of 5-HT by either p-chlorophenylalanine or 5,7-dihydroxytryptamine, did not prevent the syndrome caused by 5-methoxy-N,N-dimethyltryptamine, a 5-HT receptor agonist. Pretreatment with methysergide, but not phenoxybenzamine or pimozide, prevented the syndrome caused by 5-methoxy-N,N-dimethyltryptamine. Conversely, 5-HT depletion prevented the syndrome caused by monoamine oxidase inhibitor and levodopa; behavioral response was restored in p-chlorophenylalanine-pretreated rats by 5-hydroxytryptophan. Methysergide prevented the syndrome caused by monoamine oxidase inhibitor and levodopa, but phenoxybenzamine or pimozide did not. Intraventricular 5-HT or dopamine also caused the behavioral syndrome after monoamine oxidase inhibition. p-Chlorophenylalanine pretreatment prevented the syndrome caused by dopamine, but did not prevent the syndrome caused by 5-HT. Our results suggest that systemic levodopa or intraventricular dopamine produces the behavioral signs through 5-HT mechanisms; endogenous catecholamine mechanisms are not involved directly in either the cause or expression of the behavioral syndrome.

Aminooxyacetic Acid↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization.

The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control.

Black or African American↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination.

In an investigation of the antigenicity and reactogenicity of four smallpox vaccines, 786 children received primary percutaneous vaccination with vaccine in one of three concentrations, 10(6), 10(7), or10(8) pock-forming units/ml. Dose-response curves indicated that the three licensed vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membrane, and the Lister vaccine) had similar potencies, but the CV-1 strain was about 10-fold less infectious. CV-1 also produced smaller skin lesions than the other three vaccines, and the incidence of fever in CV-1 vaccines who developed either "major reactions" or serum antibody was not significantly different from that in children in all vaccine groups with no evidence of "take." Hemmagglutination-inhibiting antibody was consistently seen in individuals who received potent New York City and Lister vaccines, and neutralizing antibody was induced in 82%-85% of children in this group who had some evidence of take (production of hemagglutination-inhibiting antibody or or major reaction). Only 30% of CV-1 vaccines with takes produced neutralizing antibody. Minor complications occurred in all groups, but most often in children who received the New York City strains."

Animals↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination.

A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary "take." Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines.

Antibody Formation↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary subcutaneous vaccination.

As part of a large study designed to develop schedules for smallpox immunization with reduced morbidity, 799 children received primary immunization with subcutaneous vaccine. Four vaccines (New York City Board of Health calf lymph, New York City chorioallantoic membrane, CV-1 and Lister) at three dosages (l0(3), 10(4), 10(5) pock-forming units) were administered. Eighty-two percent responded with hemagglutination-inhibiting antibody at one month, and only 22% with neutralizing antibody. There was no correlation between concentration of vaccine and antibody response. The CV-1 strain was slightly but significantly less likely to induce antibody than the other three vaccines. Subcutaneous vaccination was not associated with significant temperature elevation in general. However, some children developed erythema at the vaccination site or a swollen arm, and fever did tend to occur in this small group. Four children developed nonspecific vaccinia-related rashes, and one had generalized vaccinia.

Antibody Formation↗
PubMed1977

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination.

Six months after subcutaneous vaccination with one of four smallpox vaccines, 655 children were challenged with a standard percutaneous smallpox vaccine. Response to reimmunization was characterized by a significant acceleration and diminution of skin response, but not to the degree seen in an equivalent group who had received their primary immunization percutaneously. Fever after revaccination was absent if there had been a "take" with primary subcutaneous vaccination. The overall incidence of minor vaccine-related complications with revaccination was 2-1/2%. The neutralizing antibody response to revaccination was markedly reduced, as compared to that of children who received either one or two successful percutaneous vaccinations. Subcutaneous vaccination followed by percutaneous vaccination is not recommended as a schedule for smallpox immunization, because complications are not avoided, and the incidence and mean titer of resultant neutralizing antibody are low.

Antibody Formation↗
PubMed1977

Actions of iontophoretic phenytoin and medazepam on hippocampal neurons.

In rats anesthetized with methoxyflurane, phenytoin (DPH) and medazepam (MDZ) were administered iontophoretically to pyramidal and granule cells discharging spontaneously or being driven by acetylcholine or glutamic acid. The objectives were to determine if: 1) these anticonvulsant agents exert direct effects on the rates of discharge of hippocampal neurons; 2) similarities exist between responses elicited by DPH and MDZ; and 3) pyramidal and granule cells differ in their responsiveness to the drugs. The firing rates of 38% of spontaneously active neurons were reduced by iontophoretic DPH. The incidence of depression by DPH depended upon the pretest discharge rates of the cells. Only 5% of cells with spontaneous rates less than 12/sec were depressed by DPH, but 80% with rates faster than 12/sec were inhibited. MDZ depressed 79% of spontaneously firing neurons regardless of pretest discharge rate. A majority of neurons whose firing rates were facilitated by either acetylcholine or glutamate were depressed by DPH or MDZ ejected iontophoretically. Pyramidal and granule cells responded similarly to putative transmitters, but differentially to the drugs. MDZ depressed a much greater proportion of spontaneously active granule cells then DPH. Phenytoin and MDZ differed with regard to the incidence of depression of spontaneous discharges, inhibition of slow firing cells, the proportion of granule cells depressed, and the duration of effect. These differences may be due to potency and pharmacokinetic factors or dissimilar mechanisms of action when the compounds are applied directly to single neurons.

Animals↗