Biomedical subjects

J C Cole

Publications and source records attributed to J C Cole.

At least 19 recordsLinked to original sources

PubMed1998

Directional preferences of intermolecular contacts to hydrophobic groups.

Analysis of data from the IsoStar library shows that many hydrophobic groups exhibit strikingly strong directional preferences in their intermolecular interactions. Specific directional interactions may occur because of the large quadrupole moments of many aromatic ring systems, the residual electropositive charge on most carbon-bound H atoms and the effects of polarization on soft hetero-ring atoms such as sulfur. In consequence, the binding of a hydrophobic group to a hydrophobic protein cavity is not simply a matter of matching complementary shapes. Directional preferences of nonbonded contacts to hydrophobic groups may need to be taken into account in parameterizing the next generation of protein-ligand docking programs.

Databases, Factual↗

PubMed1998

Recurrent aggressive episodes entrain ultradian heart rate and core temperature rhythms.

The present study was designed to investigate the effects of recurrent aggressive episodes on the synchrony of autonomic circadian and ultradian rhythms. Eight aggressive male rats were entrained to a reverse 12 h:12 h light-dark cycle and then implanted with telemetry senders to continuously monitor heart rate (HR) and core temperature (Tc). The amplitude and the time of the peak (acrophase) for each of the circadian and ultradian oscillations were quantified by nonlinear, least-squares, multioscillator cosinor analysis that included the first four harmonics of the circadian rhythm. After recovery from surgery, the 3- and 5-cycle/day ultradian rhythms of HR and Tc were the prominent ultradian components that were synchronized to the light-dark cycle. First, the resident males confronted a male intruder daily at lights-off (0800 hours) for a period of 3 weeks. Second, after a 3-week recovery period, 15 daily aggressive confrontations were scheduled, with the intruders being introduced at 1200 hours. During the course of the confrontations the amplitude of 3- and 5-cycle/day oscillations in HR and Tc decreased, whereas the hemicircadian (2 cycles/day) rhythm amplitude doubled with minor changes of the circadian amplitude. The hemicircadian acrophase coincided with the time of the confrontation most clearly, and this alignment lasted for more than 1 week after the last social confrontation, even in the absence of a reminder. We interpret the synchronization of the hemicircadian acrophases to the time point of social confrontations as anticipating the physiological demands of the aggressive encounters.

Activity Cycles↗

PubMed1997

IsoStar: a library of information about nonbonded interactions.

Crystallographic and theoretical (ab initio) data on intermolecular nonbonded interactions have been gathered together in a computerised library ('IsoStar'). The library contains information about the nonbonded contacts formed by some 250 chemical groupings. The data can be displayed visually and used to aid protein-ligand docking or the identification of bioisosteric replacements. Data from the library show that there is great variability in the geometrical preferences of different types of hydrogen bonds, although in general there is a tendency for H-bonds to form along lone-pair directions. The H-bond acceptor abilities of oxygen and sulphur atoms are highly dependent on intramolecular environments. The nonbonded contacts formed by many hydrophobic groups show surprisingly strong directional preferences. Many unusual nonbonded interactions are to be found in the library and are of potential value for designing novel biologically active molecules.

Biochemical Phenomena↗

PubMed1996

Plus-maze retest profile in mice: importance of initial stages of trail 1 and response to post-trail cholinergic receptor blockade.

Recent research has shown that a single undrugged prior experience of the elevated plus-maze produces significant behavioural changes upon 24-h retest in rats and mice. Typically, when reexposed to the maze, animals display an increased avoidance of the open arms and a corresponding preference for the enclosed sections of the apparatus. Using ethological analyses, the present series of experiments sought to further characterize this phenomenon in mice and to determine whether or not it involves cholinergic receptor mechanisms. Results confirmed that behaviour during Trial 2 is markedly different to that seen on initial exposure, and that such changes are independent of the duration of Trial 1 (2 vs. 5 min). Retest behavioural changes included reduced entry latencies, reduced open arm entries, less time on the open arms and centre platform, lower levels of exploratory head-dipping, and increased entries into and time spent in the closed arms. The importance to the retest phenomenon of the first few minutes of initial exposure was further suggested by min-by-min analyses of the behaviour of animals naive to the maze. Results showed that behaviour during the first min is characterized by high levels of risk assessment from the centre platform and relatively low, but equal, levels of open- and closed-arm exploration. From min 2 onwards, however, behaviour showed a marked change with increasing open arm/centre platform avoidance, increasing closed-arm preference, and decreasing levels of risk assessment and exploratory head-dipping. Thus, it would appear that this within-session aversive learning transfers between sessions to account for behavioural profiles on retest. Irrespective of the duration of Trial 1 (2 or 5 min), posttrial administration of the muscarinic antagonist, scopolamine (0.1-1.0 mg/kg), failed to significantly alter the behavioural changes seen between trials. Data are discussed in relation to the apparent sensitization of fear produced by plus-maze exposure, its possible relation to phobia acquisition, and the need for further research on underlying mechanisms.

Animals↗

PubMed1996

Interrater reliability of the written expression subtest of the Peabody Individual Achievement Test-Revised: an adolescent and adult sample.

This study examined the interrater reliability of the measure of written expression in the Peabody Individual Achievement Test-Revised. A sample more diverse in years of education and age than the normed population was used in this study. Fifty subjects from California, comprised of 72% females and 74% Caucasians, and ranging in age from 13 to 46, comprised the sample. Subjects were administered the "box" prompt from the PIAT-R Written Expression subtest (Level II). Interrater reliability for these scores was within the same range as the values provided in the manual once restriction of range was corrected.

Achievement↗

PubMed1996

Antibiotic prophylaxis in percutaneous endoscopic gastrostomy.

OBJECTIVES: The benefit of antibiotic prophylaxis in percutaneous endoscopic gastrostomy is controversial. The aim of this study is to determine whether prophylactic antibiotic treatment with Cefazolin reduces the incidence of peristomal infection after percutaneous endoscopic gastrostomy. METHODS: Of the 131 hospitalized or nursing home patients referred for percutaneous endoscopic gastrostomy, 115 were enrolled in a prospective randomized double-blind placebo controlled trial. Sixty-one (group 1) were randomized in a double-blind fashion and received either Cefazolin or saline pregastrostomy. Fifty-four patients (group 2) were on antibiotics for prior medical indications pregastrostomy. Patients had their peristomal area evaluated on a daily basis for 1 wk after gastrostomy. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0 to 3; a maximum score of 8 or higher or the presence of pus was criteria for infection. RESULTS: Wound infection occurred in 4 of 30 (13%) participants receiving Cefazolin and in 6 of 31 (19%) participants receiving saline (p > 0.5). In the 54 patients on antibiotics for prior indications, wound infection was observed in 2 subjects (3%). This finding was a significant difference when compared with the placebo group (p < 0.02). CONCLUSIONS: A single dose of Cefazolin prophylaxis does not reduce the overall peristomal wound infection in percutaneous endoscopic gastrostomy. Patients receiving prior extended antibiotic therapy have fewer peristomal wound infections.

Anti-Bacterial Agents↗

PubMed1995

Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against alpha 2-adrenoceptor mediation.

The influence of alpha 2-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5-4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significant anxiolytic-like effects on standard spatiotemporal measures at 2.0-4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective alpha 2-adrenoceptor antagonist, idazoxan (0.63-5.0 mg/kg), exerted much weaker behavioural effects in the maze while the alpha 2-adrenoceptor agonist, clonidine (0.01-0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.

Animals↗

PubMed1995

Profile of action of 5-HT3 receptor antagonists, ondansetron and WAY 100289, in the elevated plus-maze test of anxiety of mice.

The effects of ondansetron (0.001-0.1 mg/kg) and the novel 5-HT3 receptor antagonist, WAY 100289 (0.01-10.0 mg/kg), on anxiety were examined in male mice using an ethological version of the elevated plus-maze paradigm. This procedure involves scoring specific aspects of defensive behaviour in addition to the more usual spatiotemporal measures. Results show that, at the doses tested, neither compound produced a behavioural profile consistent with anxiety reduction. Indeed, the lowest dose of ondansetron (0.001 mg/kg) produced some behavioural trends more typically associated with mild anxiety enhancement. Data are discussed in relation to the enigmatic effects of 5-HT3 receptor antagonists in animal models of anxiety. It is suggested that the large within- and between-test variability observed with these compounds may indicate an action on mechanisms other than anxiety.

Animals↗

PubMed1995

Ethological comparison of the effects of diazepam and acute/chronic imipramine on the behaviour of mice in the elevated plus-maze.

Recent clinical evidence suggests that the tricyclic antidepressant imipramine is effective against not only panic disorder but also generalized anxiety disorder. Although most animal models of anxiety appear to be insensitive to this agent, such work has almost invariably employed an acute treatment regimen. In the present study, ethological methods have been used to assess in detail the effects of acute and chronic imipramine treatment on the behaviour of male DBA/2 mice in the elevated plus-maze test. In contrast to acutely administered diazepam (1 mg/kg), which produced a significant anxiolytic profile on standard and ethological measures, neither acute nor chronic (daily, 15 days) treatment with imipramine (0-20 mg/kg) was associated with anxiety reduction. Data are discussed in relation to test sensitivity factors and the nonspecific mechanism of action of imipramine.

Animals↗

PubMed1995

Ethopharmacological analysis of the effects of putative 'anxiogenic' agents in the mouse elevated plus-maze.

The literature on the effects of anxiety-provoking agents in humans and animals is replete with inconsistent and contradictory findings as well as data that may have alternate explanations. To further our understanding in this area, ethological methods were used to assess in detail the effects of four putative anxiogenic agents in the murine elevated plus-maze test. Compounds studied were FG 7142 (1.25-10.0 mg/kg), pentylenetetrazol (PTZ; 1.875-30.0 mg/kg), isoproterenol (0.125-1.0 mg/kg), and sodium lactate (32.75-262.0 mg/kg). FG 7142 produced an anxiogenic-like profile at 10 mg/kg, an effect that could not be attributed to seizure activity or nonspecific behavioural suppression. PTZ exerted biphasic effects, with low doses (1.875-3.75 mg/kg) producing anxiolytic-like effects and high doses (20.0-30.0 mg/kg) anxiogenic-like effects. With the exception of the highest dose tested, which radically disrupted behavior, these effects of PTZ were also seen to be behaviorally specific. Although some minor behavioural changes were evident with sodium lactate and isoproterenol, neither compound altered anxiety-related measures under present test conditions. Data are discussed in relation to distinctions between anxiety and panic, and the nature of anxiety expressed in and detected by animal models.

Animals↗

PubMed1994

Anxiolytic-like effect of (S)-WAY 100135, a 5-HT1A receptor antagonist, in the murine elevated plus-maze test.

The effects of (S)-WAY 100135 ((S)-N-tert-butyl-3-(4-(2-methoxyphenyl)- piperazin-1-yl)-2-phenyl-propanamide dihydrochloride; 2.5-20.0 mg/kg), a 5-HT1A receptor antagonist, on the behaviour of male mice were examined in the elevated plus-maze test of anxiety. An ethological scoring technique was used to provide a comprehensive profile of drug action. Only minor changes in behaviour were observed at 2.5 and 5.0 mg/kg, and consisted of reductions in some (though not all) risk assessment measures. At 10 mg/kg, the compound increased percent open arm entries and percent open arm time, without altering general activity levels. This classic anxiolytic-like profile was confirmed by major reductions in risk assessment measures including protected head-dips and protected stretched attend postures. Although many of the same changes were also observed at 20 mg/kg, the absence of an effect on percent open arm time and a tendency towards increased non-exploratory behaviour suggested (1) some loss of anxiolytic activity and (2) a possible contribution of non-specific factors at higher doses. Present findings indicate that (S)-WAY 100135 produces clear anxiolytic-like effects in the murine elevated plus-maze, a profile that can be distinguished from that produced by 5-HT1A receptor partial agonists in the same test.

Animals↗

PubMed1994

Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol.

Buspirone is renowned for its highly inconsistent effects in animal models of anxiety. In the present study, the effects of acute (0.63-5.0 mg/kg) and chronic (1.25-5.0 mg/kg, daily, 15 days) buspirone treatment on the behaviour of mice in the elevated plus-maze test were assessed using a recently developed ethological scoring method. On acute administration, a selective reduction in risk assessment behaviours was observed at 1.25 mg/kg; these mild anxiolytic-like effects were maintained at higher doses (2.5-5.0 mg/kg) which also reduced measures of general activity. Similar, though more potent, effects were observed with chronic administration; the lowest dose tested (1.25 mg/kg) reduced open arm entries and total stretch attend postures while higher doses profoundly reduced all major indices of anxiety (traditional and novel) and, concomitantly, suppressed total entries and rearing. Acute administration of haloperidol (0.0125-0.1 mg/kg) appeared to mimic the behavioural suppressant effects of buspirone without selectively affecting anxiety-related measures at any dose. It is suggested that the anti-anxiety and behavioural suppressant profile of buspirone may reflect combined action at 5-HT1A and D2 receptors, respectively. Results are discussed in relation to the utility of risk assessment as a sensitive index of anxiety in models based upon unconditioned behaviour.

Animals↗

PubMed1994

"Cohort removal" induces hyperthermia but fails to influence plus-maze behaviour in male mice.

Mice removed last from their home cage display elevated body temperature compared with those removed first. This stress-induced hyperthermia (SIH) response has been reported for Swiss and NMRI mice and has been forwarded as a model of anticipatory anxiety. In the present study, the effects of order of removal from the home cage (cohort removal) on body temperature and behaviour in the elevated plus maze have been examined in group-housed male DBA/2 mice. Results confirm the basic phenomenon of SIH in this strain, with mice removed from the home cage in positions 4-10 displaying a significantly higher mean rectal temperature compared with those removed in positions 1-3. Despite this observation, however, detailed ethological analysis failed to reveal any significant effect of cohort removal on behaviour displayed in the elevated plus-maze paradigm. Data are discussed in relation to variations in the nature of reactions evoked in different animal models of anxiety.

Animals↗

PubMed1994

Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan.

Flesinoxan is a potent and selective 5-HT1A receptor agonist. In this study, the effects of this compound on behavior in the murine elevated plus-maze have been assessed using a recently developed ethological scoring method. Results show that, at low doses (0.1-0.5 mg/kg), flesinoxan inhibited risk assessment behaviors (stretched attend postures and closed arm returns) indicative of a reduction in anxiety. These effects were maintained at a higher dose of 1.0 mg/kg, which also increased percent open entries and time spent on the central platform and open arms. However, this more convincing anxiolytic profile was associated with significant reductions in total arm entries and rearing, suggesting a combination of anxiolysis and behavioral suppression at high doses. The plus-maze profile observed with flesinoxan is very similar to that previously reported for 8-OH-DPAT in the same test but, despite superficial similarities, can be distinguished from that seen with buspirone. Data are discussed in relation to behavioral similarities and differences between 5-HT1A receptor agonists, and the advantages of a more detailed approach to the analysis of plus-maze behavior.

Animals↗

PubMed1994

Dopamine D1 and D2 receptor ligands modulate the behaviour of mice in the elevated plus-maze.

To further our understanding of the potential role of dopamine in mechanisms of anxiety, the effects of four dopamine receptor ligands were examined in an ethological version of the murine elevated plus-maze test. The D1 receptor partial agonist, SKF 38393 (2.5-20.0 mg/kg), had minimal behavioural activity in this test, whereas the selective D1 receptor antagonist, SCH 23390 (0.025-0.2 mg/kg), had dose-dependent but behaviourally nonspecific effects. Quinpirole (0.0625-0.5 mg/kg), a D2 receptor agonist, had no effects at low doses but severely disrupted locomotion and exploration at the highest doses tested. In marked contrast to the lack of effect or nonspecific effects seen with the other ligands tested, the D2 receptor antagonist, sulpiride (2.5-20.0 mg/kg), produced an unambiguous anxiolytic-like profile under present test conditions. Although none of the doses tested adversely affected general activity, clear antianxiety effects were observed on both traditional and novel (i.e., risk assessment) behavioural measures. Data are discussed in relation to the relative importance of D1 and D2 receptor mechanisms in plus-maze anxiety, and the need to further assess D2 involvement through the use of more selective compounds.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1994

Colobronchial fistula: an unusual complication of Crohn's disease.

Fistulas secondary to Crohn's disease occur in about 33% of patients. A colobronchial fistula complicating Crohn's disease is very rare, having been reported only twice previously. We present an unusual fistula secondary to Crohn's colitis that originated from the splenic flexure and crossed the diaphragm to involve the bronchial tree.

Adult↗

PubMed1993

Influence of social isolation, gender, strain, and prior novelty on plus-maze behaviour in mice.

Behavioural baseline is a critical determinant of response to drugs and other manipulations. In the present study, the influence of several organismic and procedural variables on basal plus-maze profiles in mice were examined. The methodology incorporated traditional behavioural parameters as well as novel measures derived from ethological analysis. Experiment 1 showed that social isolation for 1-3 weeks enhanced aggression in male DBA/2 mice but did not substantially alter their behaviour on the maze. A reduction in stretch attend postures did, however, suggest a minor reduction in anxiety in socially isolated animals. In Experiment 2, males of both DBA/2 and T1 strains exhibited higher levels of general activity on the maze than their female counterparts. Although additional evidence suggested that DBA/2 (but not T1) females were less anxious than males, no major sex differences were noted. Experiment 3 revealed a significant strain difference in plus-maze profiles, with T1 males showing a lower basal level of anxiety than DBA/2 males. This study also demonstrated that DBA/2 and T1 males react very differently to prior novelty experience, with enhanced anxiety evident in the former and reduced anxiety in the latter. Together, these findings point to a range of organismic and procedural variables that may account for inconsistencies in the literature on the elevated plus-maze.

Aggression↗

PubMed1993

Anxiety enhancement in the murine elevated plus maze by immediate prior exposure to social stressors.

Anxiety has been implicated in the acute nonopioid analgesic reaction seen in defeated mice. In the present study, behavioural responses to the elevated plus-maze test were examined in male DBA/2 mice immediately following defeat by an experienced aggressive conspecific. Compared to home-cage controls, defeat reduced total arm entries and rearing, although anxiety enhancement was indicated by decreases in percent open-arm entries and percent time spent on the open arms. These effects were accompanied by significant increases in nonexploratory behaviour (movement arrest and grooming) and risk assessment (closed arm returns, protected head dipping, and stretch-attend postures). This anxiogenic effect of social defeat was partially replicated in mice merely exposed to the scent of an aggressive male conspecific. The specificity of present findings to socially relevant stressors was confirmed by the general lack of effect on plus-maze behaviour of prior exposure to a novel cage or to interaction with a nonaggressive male. Present results are not only consistent with the anxiety hypothesis of defeat analgesia but also show that the elevated plus-maze test is sensitive to alterations in anxiety produced by ecologically relevant stimuli. Possible implications for pharmacological studies are discussed.

Agonistic Behavior↗