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Biomedical subjects

J L Howard

Publications and source records attributed to J L Howard.

At least 19 recordsLinked to original sources
PubMed1992

Effects of tandospirone in three behavioral tests for anxiolytics.

The azapirone putative anxiolytic tandospirone was evaluated in two behavioral screening methods that identify known azapirone anxiolytics and one method that identifies only sedative-hypnotic anxiolytics. Tandospirone produced a large increase in punished key-pecking for food in pigeon and a large increase in cork gnawing in rat. It did not produce a large increase in punished lever-pressing for food in rat, a result that to some extent contradicts reports from other laboratories. It was equipotent with buspirone in pigeon, but in rat it was ten times less potent than buspirone in disrupting the lever-press response and increasing cork gnawing. The results indicate that tandospirone is qualitatively similar to the other azapirone anxiolytics buspirone, gepirone and ipsapirone and is different from sedative-hypnotic anxiolytics.

Animals↗
PubMed1991

Characterization of the major promoter for the plasmid-encoded sucrose genes scrY, scrA, and scrB.

Sucrose genes from a Salmonella thompson plasmid were cloned in Escherichia coli K-12. A physical map and a genetic map of the genes were constructed, revealing strong homology with the scr regulon from the Salmonella typhimurium plasmid pUR400. Two promoters were examined after being subcloned into transcriptional fusion vectors. Primer extension analysis and site-directed mutagenesis were used to identify the precise location of the promoter of scrY, scrA, and scrB. Transcription from this promoter was regulated over a 1,000-fold range by the combined effects of ScrR-mediated repression and catabolite repression. A putative cyclic AMP receptor protein binding site centered 72.5 bp upstream of the start point of transcription of scrY appeared to be essential for full activity of the scrY promoter. Transcription from the putative scrK promoter was far less sensitive to repression by ScrR. In ScrR+ cells, readthrough transcription from the putative scrK promoter into scrY accounted for less than 10% of scrY expression.

Amino Acid Sequence↗
PubMed1991

Job sharing: a viable option for the clinical nurse specialist.

NUMEROUS WORK TIME options have been developed to attract, retain and meet the various needs of nurses. Job sharing, a work option little known to nurses, can be a successful alternative for balancing professional and personal lifestyle. The business literature supports job sharing and other innovative work options as successful mechanisms in retaining quality employees in their respective professions. After exploring the literature in this area, a proposal for job sharing the oncology clinical nurse specialist (CNS) position was presented to the Personnel Director and Vice President of Nursing at our institution. The proposal addressed the advantages and disadvantages of the concept. These included: (1) scheduling flexibility, (2) reduced absenteeism and turnover, (3) increased productivity, (4) handling fringe benefits, and (5) job satisfaction. The proposal was accepted, and the job sharing position has been successfully implemented for more than 2 years now. This paper describes issues relevant to designing and implementing job sharing in a CNS position.

Employee Performance Appraisal↗
PubMed1990

Benzodiazepine receptor binding activity of 8-substituted-9-(3-substituted-benzyl)-6-(dimethylamino)-9H-purines.

A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50 = 0.011 microM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule.

Animals↗
PubMed1990

Benzodiazepine receptor binding activity of 9-(1-phenylethyl)purines.

Several alpha-methyl analogues of the 9-benzylpurines that bind to the benzodiazepine receptor (BZR) were synthesized and tested for BZR-binding activity. Although introduction of a m-amino group and an 8-bromo substituent gave an additive increase in BZR affinity with 9-(3-aminobenzyl)-8-bromo-6-(dimethylamino)-9H-purine (4), addition of an alpha-methyl group to 4 resulted in a loss in BZR affinity. This loss in affinity is apparently due to repulsive, steric interactions between the 8-bromo and 9-(1-phenylethyl) substituents, which results in a conformation that is not optimal for interaction with the BZR. Several compounds were tested on a modified Geller-Seifter conflict schedule, but none exhibited significant anxiolytic activity.

Animals↗
PubMed1990

Bone scintigraphy in the evaluation of extraskeletal injuries from child abuse.

Bone scintigraphy is a valuable imaging modality in the examination of the battered child. It is often used to evaluate skeletal trauma. However, bone scans may also reveal subtle and unusual scintigraphic findings that, if recognized, can lead to the diagnosis of intracranial, visceral, and soft-tissue injury. Several cases of child abuse in which bone scan findings suggested the presence of injuries other than skeletal trauma are presented.

Bone and Bones↗
PubMed1989

Benzodiazepine receptor binding activity of 6,9-disubstituted purines.

A series of 6,9-disubstituted purines were tested for their ability to bind to the benzodiazepine receptor in rat brain tissue. One of the most active compounds was 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (44) with an IC50 = 0.9 microM, which was only 4.5-fold higher than the IC50 for chlordiazepoxide. Substitution of a 3-aminobenzyl or 3-hydroxybenzyl group at the 9-position of 6-(dimethylamino)purine led to over a 50-fold increase in receptor affinity. Compound 44 did not exhibit significant anxiolytic activity, nor did anticonvulsant activity correlate with relative receptor binding affinity.

Animals↗
PubMed1988

Effects of chlordiazepoxide, pentobarbital, buspirone, chlorpromazine, and morphine in the stretched attend posture (SAP) test.

The stretched attend posture (SAP) in the mouse is an investigatory forward elongation of the body in a novel environment. In a previous study, the anxiolytics diazepam, clobazam, and phenobarbital reduced SAP, and low doses of the non-anxiolytics imipramine and chlorpromazine were ineffective, results which prompted the investigator to propose the SAP test as a screening method for anxiolytics. However, diazepam and clobazam also increased immobility. In the present study, the anxiolytics chlordiazepoxide, pentobarbital, and buspirone and behaviorally active doses of the non-anxiolytics chlorpromazine and morphine reduced SAP and tended to increase immobility. We concluded that therapeutic-class specificity has not been demonstrated for the SAP test.

Animals↗
PubMed1988

Cue properties of oral and transdermal nicotine in the rat.

In a standard two-lever drug discrimination paradigm, rats were trained to discriminate nicotine 0.5 mg/kg PO from saline. Injections occurred 15 min before the session. Subjects reached the training criterion in a mean of 38 sessions. Nicotine PO, SC, and IP generated similar dose-effect curves (ED50 = 0.073 mg/kg PO, 0.076 mg/kg SC, 0.090 mg/kg IP); the dose-effect curve for transdermal (TD) administration fell approximately 1 log unit to the right (ED50 = 1.34 mg/kg). The percentage of rats choosing the nicotine-appropriate lever peaked at 15 min and gradually decreased to 50% or less by 180 min for nicotine PO and TD, a time-decay function similar to that previously shown for SC administration. The nicotinic cholinergic agonist cytisine (0.5-8.0 mg/kg) PO and TD produced up to 56% nicotine-appropriate responding, while the muscarinic cholinergic agonist arecoline (1.0-4.0 mg/kg) PO and TD produced only saline-appropriate responding. The nicotine cue did not generalize to the cholinergic antagonist mecamylamine (0.125-0.5 mg/kg) PO or TD; mecamylamine 0.5 mg/kg PO but not TD completely blocked the PO and TD nicotine cues. These results show that an approximately equal cue occurs with PO, IP, and SC administration, and that the TD cue is considerably weaker. The significance of the procedure as an animal analog of human transdermal nicotine intake is discussed.

Administration, Cutaneous↗
PubMed1988

Conditioned defensive burying as a model for identifying anxiolytics.

Rats exposed to a presumably aversive stimulus such as electric shock respond by heaping litter on the source, a behavior known as conditioned defensive burying (CDB). Because some anxiolytics suppress this behavior, CDB has been proposed as a screening method for anxiolytics. We tested the effects of the conventional anxiolytics chlordiazepoxide (4-32 mg/kg) and meprobamate (75-125 mg/kg), the novel anxiolytic buspirone (8-64 mg/kg), the antidepressant imipramine (4-16 mg/kg), the opiate analgesic morphine (2-8 mg/kg), and the antipsychotic chlorpromazine (1-16 mg/kg) on CDB. Chlordiazepoxide, meprobamate, imipramine, and morphine significantly suppressed CDB, but chlordiazepoxide did so only at a dose that reduced general activity. Buspirone and chlorpromazine did not suppress CDB at doses that reduced activity. There were some methodological differences from previous studies. We conclude that the test as constituted in this study lacks drug-class specificity. The necessity of distinguishing between specific reduction of burying and general reduction of activity is emphasized.

Animals↗
PubMed1987

Metoclopramide potentiates d-amphetamine-induced hypermotility and stereotypy in rat.

The substituted benzamide metoclopramide has been reported to block the behavioral effects of dopamine agonists, whereas its congener sulpiride potentiates these effects. We injected metoclopramide 2.0, 4.0, or 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5 mg/kg IP and measured locomotion for 3 hr. We injected metoclopramide 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5, 3.0, or 6.0 mg/kg IP and measured stereotypy for 3 hr. Metoclopramide potentiated the effects of all doses of d-amphetamine on both measures; peak effects occurred in the second or third hr after d-amphetamine injection. Metoclopramide alone tended to reduce behavior. The results suggest that metoclopramide is qualitatively similar to sulpiride in its interaction with d-amphetamine, and that metoclopramide's mechanism of action is not a simple dopaminergic antagonism. Clinicians are advised that metoclopramide, which is presently extensively for gastrointestinal and other disorders, may interact adversely with drugs that affect dopaminergic function.

Animals↗
PubMed1986

The staircase test: some evidence of nonspecificity for anxiolytics.

In the staircase test, a naive mouse is placed in a Plexiglas chamber containing a five-step staircase, and the number of rearings and steps climbed are recorded for 3 min. A claim for drug-class specificity has been made because conventional anxiolytics reduced rearings at doses that did not reduce steps climbed, while non-anxiolytics affected both measures in parallel. In the present study chlordiazepoxide, meprobamate, and ethanol registered the expected true positive effect by reducing rearings at doses that did not reduce steps climbed. Nicotine, which has some clinical anxiolytic action, registered a small true positive. The benzodiazepine anxiolytic alprazolam reduced both measures, a false negative, although it reduced rearings more than steps climbed. The putative novel anxiolytics CGS 9896, ketanserine, and tracazolate registered negatives, as did the known clinical anxiolytic buspirone. The non-anxiolytics phencyclidine and phenacetin registered true negatives, but morphine registered a clear false positive. The anxiogenics FG 7142 and pentylenetetrazol produced no significant effects. Because of the equivocal false negative for alprazolam, the clear false negative for buspirone, and the clear false positive for morphine, we concluded that the test lacks the degree of therapeutic-class specificity previously proposed but may still be useful in basic research.

Animals↗
PubMed1986

Similar effects of antidepressant and non-antidepressant drugs on behavior under an interresponse-time greater than 72-s schedule.

Antidepressant drugs were reported to decrease responses and increase reinforcements in water-deprived male albino rats pressing a lever for water on a schedule requiring a pause of at least 72 s between responses (IRT greater than 72). Subsequently other investigators, using food-deprived ovariectomized hooded rats pressing a lever for food, showed that antipsychotic drugs produced the same effect as antidepressants. Because methodologies differed somewhat, the present study was designed to replicate closely the experimental conditions of the original studies, e.g., same strain and sex, same reinforcer, similar baseline behavior. In this study the antidepressant imipramine, the antipsychotics chlorpromazine and haloperidol, and to some extent the anxiolytic buspirone produced qualitatively similar effects - decreased responses and increased reinforcements - although there were some quantitative differences. This result, and other results showing that some antidepressants increase responses and decrease reinforcements, suggest that the IRT greater than 72-s task lacks specificity as a screening method for antidepressants.

Animals↗
PubMed1984

Effect of ovarian hormones on conflict behavior.

We injected ovariectomized female rats with estrogen and progesterone. Some of the injection regimens used are known to induce estrus, while other do not. The effects of these treatments on operant behavior were evaluated. Operant behavior was maintained under a reinforcement schedule, one segment of which involved experimentally induced conflict. Such behaviors previously have been shown to be modified by anti-anxiety drugs. Those hormone treatments effective in inducing estrus had behavioral effects similar to the effects observed for established anti-anxiety agents. Hormone-injection regimens not capable of inducing estrus were without effect on operant behavior. Our findings suggest that the reproductive cycles of female rats are associated with behavioral changes which may be indicative of changing anxiety levels mediated in part by changing titers of ovarian hormones. We suggest that the evaluation of hormonal influences on operant behaviors sensitive to tranquilizers should be a useful model system for studying possible mechanisms underlying emotional changes associated with reproductive cycles.

Animals↗
PubMed1983

Animal models used in prediction of antidepressant effects in man.

The discovery of bupropion's potential antidepressant activity resulted from studies of its behavioral effects in a number of animal models of depression. These animal models and data pertaining to their selectivity for other standard antidepressant drugs are reviewed.

Animals↗