Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 19 recordsLinked to original sources

PubMed2001

Genetic evidence for a family structure in stable social aggregations of the Australian lizard Egernia stokesii.

In this study we used data from six unlinked microsatellite loci to examine stable aggregations of Egernia stokesii, from a population in the southern Flinders Ranges of South Australia. We show that these aggregations are comprised of breeding partners, their offspring from two or more cohorts, and related adults, providing the first genetic evidence of a family structure in any lizard species. Despite this high level of relatedness within aggregations, most breeding pairs were unrelated and partners were less closely related to each other than they were to other potential within-group partners. Where individuals dispersed, both sexes usually moved to social groups close to their natal group. Although both sexes showed natal philopatry, there was some evidence that females in groups were more related than males in groups. These data suggest that an active choice of unrelated partners and male-biased dispersal may be the mechanisms used by E. stokesii to avoid inbreeding within groups.

Animals↗

PubMed2001

The managed care contract: the blueprint for monitoring agreements.

Healthcare providers generally undertake monitoring programs of managed care arrangements as a way of analyzing financial performance, uncovering lapses in contractually mandated performance that might expose the organization to financial loss, and gathering information that can be helpful in renegotiating the contract or negotiating new arrangements. To secure access to the information needed to achieve these goals, the provider should ensure that the contract spells out the information required, the health plan's obligations to supply this information, and the consequences of the plan's failure to meet those obligations. Such consequences may include financial penalties for the plan and special termination rights for the provider. Without a contractually explicit assurance that the needed information will be available, a provider may find itself with no way to achieve its contract-monitoring goals.

Contract Services↗

PubMed2000

Hybrid-cluster protein (HCP) from Desulfovibrio vulgaris (Hildenborough) at 1.6 A resolution.

The three-dimensional structure of the hybrid cluster protein from Desulfovibrio vulgaris (Hildenborough) has been determined at 1.6 A resolution using synchrotron X-ray radiation. The protein can be divided into three domains: an N-terminal mainly alpha-helical domain and two similar domains comprising a central beta-sheet flanked by alpha-helices. The protein contains two 4Fe clusters with an edge-to-edge distance of 10.9 A. Four cysteine residues at the N-terminus of the protein are ligands to the iron atoms of a conventional [4Fe-4S] cubane cluster. The second cluster has an unusual asymmetric structure and has been named the hybrid cluster to reflect the variety of protein ligands, namely two mu-sulfido bridges, two mu(2)-oxo bridges, and a further disordered bridging ligand. Anomalous differences in data collected at 1.488 A and close to the iron edge at 1.743 A have been used to confirm the identity of the metal and sulfur atoms. The hybrid cluster is buried in the center of the protein, but is accessible through a large hydrophobic cavity that runs the length of domain 3. Hydrophobic channels have previously been identified as access routes to the active centers in redox enzymes with gaseous substrates. The hybrid cluster is also accessible by a hydrophilic channel. The [4Fe-4S] cubane cluster is close to an indentation on the surface of the protein and can also be approached on the opposite side by a long solvent channel. At the present time, neither the significance of these channels nor, indeed, the function of the hybrid cluster protein is known.

Amino Acid Sequence↗

PubMed2000

The effect of the dopamine D2 receptor antagonist raclopride on the pattern of licking microstructure induced by midazolam in the rat.

The role of dopamine in the effects of midazolam on ingestive behaviour was investigated using microstructural analysis of licking behaviour in the rat. Midazolam (1.8 mg/kg i.p.) was administered alone or in combination with the dopamine D2 receptor antagonist raclopride (0.1 and 0.3 mg/kg i.p.). The effect on licking patterns during 60 s exposure to a range of concentrations of sucrose solution was recorded using an automated lickometer. Midazolam increased the total number of licks via an increase in mean bout duration, an effect consistent with the proposal that these drugs enhance palatability. Midazolam also decreased the intrabout lick rate, probably because of muscle relaxant effects. Pre-treatment with raclopride blocked midazolam-induced increases in mean bout duration, at doses that by themselves were ineffective, but did not reverse the decrease in intrabout lick rate. These data point to the interdependence of benzodiazepine and dopamine substrates in the mediation of palatability.

Animals↗

PubMed2000

Depressive symptoms in stable chronic schizophrenia: prevalence and relationship to psychopathology and treatment.

The prevalence and correlates of the depressive syndrome were explored in a population of 120 patients with stable, chronic schizophrenia living in the community. The presence of clinically significant depressive symptoms was defined by a score of 17 or greater on the Beck Depression Inventory. Patients were examined to assess severity of schizophrenic symptoms and medication side-effects. Sixteen of the 120 patients (13.3%) had significant depressive symptoms. Depressive symptoms were significantly correlated with the hostility/suspiciousness (P<0.0001), the positive symptom (P=0.0009) factor of the BPRS and with scores on the Significant Others Scale, a measure of patients' perceived lack of social support (P=0.0004). The association between depression and akathisia approached significance (P=0.007). There was no correlation with demographic variables, alcohol intake, antipsychotic dosage or anticholinergic dosage. Using a scale that rates the subjective aspects of the depressive syndrome, we found no evidence of a relationship between depression and negative symptoms in this population. These results indicate that persistent depressive symptoms in stable patients in the community are related to the degree of persistent positive psychotic symptoms, patient perceptions of social support and, weakly, to the degree of akathisia but not other aspects of antipsychotic treatment.

Adolescent↗

PubMed2000

Zotepine for schizophrenia.

BACKGROUND: Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms OBJECTIVES: To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), Dialog Corporation Datastar service (1999), MEDLINE (1966-1999), and PsycLIT (1974-1999) were undertaken. References of all identified studies were searched for further trials. Knoll Pharmaceuticals and authors of trials were contacted. SELECTION CRITERIA: All randomised clinical trials that compared zotepine to other treatments for people with schizophrenia or other psychoses were included. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) and numbers needed to harm (NNH), were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: All outcomes were short term (4-12 weeks). Limited data suggest that zotepine is an antipsychotic, at least as effective as typical drugs. Mental state measures of 'no clinically important improvement' favour zotepine when compared to other active drugs (n=356, RR 0.8 CI 0.7-0.9, NNT 7 CI 4-22). About one third of people in both zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs. REVIEWER'S CONCLUSIONS: Zotepine may be a valuable addition to the increasing ranks of atypical antipsychotic drugs. More data from already existing studies is urgently needed to increase the confidence in the findings of this review. New data from well planned, conducted and reported long term pragmatic randomised trials are necessary. Otherwise clinical use of zotepine will be based on speculation on the meaning of the findings of short explanatory trials for everyday practice.

Antipsychotic Agents↗

PubMed2000

Molecular phylogeny of the large carpenter bees, genus Xylocopa (Hymenoptera: apidae), based on mitochondrial DNA sequences.

Carpenter bees, genus Xylocopa Latreille, a group of bees found on all continents, are of particular interest to behavioral ecologists because of their utility for studies of the evolution of mating strategies and sociality. This paper presents phylogenetic analyses based on sequences of two mitochondrial genes cytochrome oxidase 1 and cytochrome b for 22 subgenera of Xylocopa. Maximum-parsimony and maximum-likelihood methods were used to infer phylogenetic relationships. The analyses resulted in three resolved clades of subgenera: a South American group (including the subgenera Stenoxylocopa, Megaxylocopa, and Neoxylocopa), a group including the subgenera Xylocopa s.s. and Ctenoxylocopa, and an Ethiopean group (including the subgenera Afroxylocopa, Mesotrichia, Alloxylocopa, Platynopoda, Hoploxylocopa, and Koptortosoma). The relationships between the 11 other subgenera and the resolved clades are unclear. Within the Ethiopian group we found a clear separation of the African and the Oriental taxa and apparent polyphyly of the subgenus Koptortosoma. Using an evolutionary rate for ants, we investigated whether Gondwana vicariance or more recent dispersal events could best explain the present-day distribution of subgenera. Although some taxa show divergences that approach Gondwanan breakup times, most divergences between geographic groups are too recent to support a vicariance hypothesis.

Animals↗

PubMed2000

Zotepine in the prevention of recurrence: a randomised, double-blind, placebo-controlled study for chronic schizophrenia.

RATIONALE: Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia. Antipsychotic drugs also require to be effective in prevention of recurrence. OBJECTIVE: This trial was designed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia. METHODS: The study was a double-blind, parallel group, 26-week comparison of zotepine (300 mg daily, with fall back to 150 mg if necessary) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months. The primary outcome measure was the time to recurrence. Other evaluations included the brief psychiatric rating scale (BPRS), the scale for the assessment of negative symptoms (SANS), the clinical global impression (CGI) severity and improvement scales, and the Simpson and Angus scale for extrapyramidal symptoms (EPS). RESULTS: Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients (4 versus 21, respectively). The estimated 26-week risk of recurrence was six times lower for zotepine than placebo (8.7% versus 52.8%; hazard ratio 0.16, 95% CI 0.053, 0.484; P<0.001). Scores on the BPRS and CGI supported the efficacy of zotepine. There was no difference between the treatments with respect to EPS. CONCLUSIONS: Zotepine is effective in preventing recurrence in patients with chronic schizophrenia. The level of EPS was not different between zotepine and placebo.

Adolescent↗

PubMed2000

Anomalous asymmetry of fusiform and parahippocampal gyrus gray matter in schizophrenia: A postmortem study.

OBJECTIVE: Anomalies of structure and asymmetry of the parahippocampal gyrus (origin of the perforant path input to the hippocampal formation in the medial temporal lobe) have been shown in some postmortem studies of schizophrenia, but previous studies have not included the fusiform gyrus (which may have a role in facial recognition and naming), adjacent to the parahippocampal gyrus on the ventral occipitotemporal surface. METHOD: The volumes of gray matter in the left and right parahippocampal and fusiform gyri were assessed with a stereological point-counting technique in the temporal lobes from formalin-fixed brains of 27 comparison subjects and 31 patients with schizophrenia. Age was a covariate and gender was a factor in the analysis. RESULTS: In relation to the comparison subjects, the schizophrenic patients (both sexes) had lower volumes of both the parahippocampal and fusiform gyri on the left side. For both structures a left-greater-than-right volume asymmetry was present in the comparison subjects, but this asymmetry was reversed in the parahippocampal and fusiform gyri of the schizophrenic patients. A sex difference was present with respect to age at onset-degree of anomaly of asymmetry for both gyri increased with age at onset in men but not in women. CONCLUSIONS: The findings add substance to the view that the sex-related dimension of symmetry/asymmetry is integral to the disease process in schizophrenia and draw attention to the fusiform gyrus as a structure of particular interest in relation to disturbances of identification and naming in psychosis.

Adult↗

PubMed2000

A placebo-controlled comparison of zotepine versus chlorpromazine in patients with acute exacerbation of schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the efficacy of zotepine in the treatment of acute episodes of schizophrenia. METHOD: Patients with acute exacerbation of schizophrenia (DSM-III-R criteria; n = 158) were allocated on a random, double-blind basis to receive zotepine (150 or 300 mg/day), chlorpromazine (300 or 600 mg/day) or placebo for 8 weeks. Symptoms were assessed on the BPRS, SANS and CGI scales at baseline and weeks 1, 2, 4, 6 and 8 and patients were assessed at these times for adverse effects. Analysis was by analysis of variance on the intent-to-treat population, with last observation carried forward. RESULTS: Mean BPRS scores improved statistically significantly more with zotepine than chlorpromazine (point estimate of difference -12.4, 95% CI -18.3 to -6.5) or placebo (point estimate of difference -12.7, 95% CI -18.6 to -6.8). Zotepine produced significantly fewer extrapyramidal symptoms (EPS) than chlorpromazine. CONCLUSION: Zotepine is an effective antipsychotic with low propensity for EPS.

Acute Disease↗

PubMed1999

Plasma norepinephrine and prediction of outcome in major depressive disorder.

BACKGROUND: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD. METHODS: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression. RESULTS: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD (n = 31, chi 2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria (n = 34, adjusted R2 = .24, p < .01) and DOS criteria (n = 31, adjusted R2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features. CONCLUSIONS: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.

Adult↗

PubMed1999

Evolution and molecular characterization of a beta-globin gene from the Australian Echidna Tachyglossus aculeatus (Monotremata).

Coinciding with a period in evolution when monotremes, marsupials, and eutherians diverged from a common ancestor, a proto-beta-globin gene duplicated, producing the progenitors of mammalian embryonic and adult beta-like globin genes. To determine whether monotremes contain orthologues of these genes and to further investigate the evolutionary relationships of monotremes, marsupials, and eutherians, we have determined the complete DNA sequence of an echidna (Tachyglossus aculeatus) beta-like globin gene. Conceptual translation of the gene and sequence comparisons with eutherian and marsupial beta-like globin genes and echidna adult beta-globin indicate that the gene is adult expressed. Phylogenetic analyses do not clearly resolve the branching pattern of mammalian beta-like globin gene lineages and it is therefore uncertain whether monotremes have orthologues of the embryonic beta-like globin genes of marsupials and eutherians. Four models are proposed that provide a framework for interpreting further studies on the evolution of beta-like globin genes in the context of the evolution of monotremes, marsupials, and eutherians.

Amino Acid Sequence↗

PubMed1998

Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study.

In a post-mortem study of cerebral asymmetry in schizophrenia it was found that asymmetry of the length from the frontal pole to the central sulcus measured dorsally over the external surface of the brain on both hemispheres, showed a gender x diagnosis interaction (p = 0.002). Female controls had a left-greater-than-right asymmetry, and the male controls had a right-greater-than-left asymmetry. This pattern was reversed in schizophrenia. The converse effect was observed on a similar measure of the occipito-parietal lobes (p = 0.028). Significant changes were not seen in measures taken around the lateral surface of the hemispheres. Further, within the patient group, the frontal lobe asymmetry was related to age of onset such that leftward asymmetrical brains were associated with a later age of onset than rightward asymmetrical brains (p = 0.0463 for the females; p = 0.0162 for the males). The occipito-parietal asymmetry was not related to age of onset. We conclude that the asymmetry of the relative distribution of tissue between frontal and posterior regions of the hemispheres is altered in schizophrenia. The findings also suggest that there is an interaction between gender and cerebral asymmetry that is critical in determining age of onset.

Age of Onset↗

PubMed1998

Temporal-lobe length is reduced, and gyral folding is increased in schizophrenia: a post-mortem study.

This post-mortem study of the brains of 29 controls and 25 patients with schizophrenia investigated the length and gyral folding of the temporal lobes, and the asymmetries and inter-relationships of these two measures. The degree of gyral folding was significantly increased in schizophrenia (p = 0.002), but the orientation of the sulci was not changed (p = 0.420). Neither gender nor side affected any of the measures of gyral anatomy, nor were there any significant interactions of these variables with diagnosis. The temporal lobes were significantly shortened in schizophrenia, on two different measures (p = 0.009, and p = 0.001), and on one of these, females had shorter temporal lobes than males (p < 0.0005). No diagnosis x side interactions were found. The temporal-lobe shortening remained after controlling for brain weight and was not statistically related to gyral folding. These two structural changes may reflect an alteration of the cortico-cortical connectivity of the brain in schizophrenia.

Aged↗

PubMed1998

Plasma norepinephrine response to a cold pressor test in subtypes of depressive illness.

Noradrenergic systems have been shown to be disordered in depressive illness. The plasma norepinephrine response to a cold pressor test was used to investigate norepinephrine activity in subtypes of depressive illness. Patients with melancholic or psychotic depression, non-melancholic depression, general anxiety disorder and normal control subjects had a cold pressor test carried out under standard conditions. Blood samples were taken to measure plasma norepinephrine during the test. The plasma norepinephrine response to a cold pressor test was reduced in the melancholic/psychotic depressed patients compared to control subjects. No other intergroup comparisons were statistically significant. These results suggest noradrenergic systems are disturbed and subresponsive to stress in melancholic/psychotic depressed patients. This does not appear related to other clinical or biochemical factors.

Adult↗

PubMed1998

Central 5-HT3 receptors in P and in AA alcohol-preferring rats: An autoradiographic study.

Considerable evidence exists for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-hydroxytryptamine (5-HT3) receptor autoradiographical investigation was performed using two genetically selected rat strains, alcohol preferring (P) and Alko alcohol (AA) alcohol-preferring rats, as well as the corresponding alcohol nonpreferring (NP) and Alko nonalcohol (ANA) alcohol-nonpreferring rats. The aim was to determine if there are any differences in 5-HT3 binding levels that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT3 binding sites, [3H]S(-)zacopride (0.5 nM) was used. Non-specific binding was measured in the presence of granisetron 10(-6) M. The [3H]S(-)zacopride binding density was measured in two subregions of the amygdaloid nucleus, frontal cortex, piriform cortex, cingulate laminae, parietal anterior cortex, parietal medial cortex, hippocampus CA1, hippocampus CA3, and entorhinal cortex. In all the brain areas investigated, the results showed no differences between AA and ANA rats. In P rats, compared to NP controls, there was a 30% lower 5-HT3 binding level in the lateral nucleus and the posteromedial cortical nucleus of the amygdala. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a general alteration of central 5-HT3 receptors, although a lower 5-HT3 receptor level in the amygdala of P rats may contribute to the phenotype of this strain of animals.

Alcohol Drinking↗

PubMed1998

Evidence for early opioid modulation of licking responses to sucrose and intralipid: a microstructural analysis in the rat.

The behavioural mechanisms underlying the effects of the opioid antagonist naloxone (0.3-3 mg/kg i.p.), and the opioid agonists morphine (0.3-3 mg/kg s.c.), and U-50, 488H (0.3-3 mg/kg s.c.) on ingestive behaviour were investigated using a microstructural analysis of licking patterns for sucrose solutions and Intralipid (fat emulsions) in a brief contact test. Naloxone dose-dependently decreased the total number of licks and the number of bouts for sucrose and Intralipid, but did not affect mean bout duration. Morphine dose-dependently increased the total number of licks and the number of bouts for both test fluids. For Intralipid but not for sucrose drinking, morphine actually decreased mean bout duration. U-50, 488H significantly affected total licks, although the dose-effect relationship showed an inverted U-shaped function. There was a dose-dependent increase in mean bout duration following administration of U-50, 488H and an increase in bout number, although only the lowest dose differed significantly from the control condition. The results show that microstructural analysis can distinguish between the effects of naloxone, morphine and U-50, 488H on licking behaviour and indicate that selective opioid receptor subtypes may be differentially involved in ingestive processes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1998

Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one in male rats.

The neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone) and benzodiazepine receptor (BZR) agonists share sedative, anxiolytic, and anticonvulsant properties. Recent evidence suggests that like BZR agonists, pregnanolone may also modulate feeding responses. The present experiments examined the behavioral mechanisms responsible for any hyperphagic effect of pregnanolone. The effect of pregnanolone (1-10 mg/kg i.p.) on the intake and microstructure of licking for two sucrose solutions (1 and 3%) in well familiarized nondeprived male rats under either light or dark conditions was examined. Pregnanolone had no effect on either intake or the duration or number of bouts of licking in these experiments, although in all cases the intrabout lick rate was significantly reduced at the highest dose. Pregnanolone (1-10 mg/kg) also failed to increase intake of a sweet wet mash in familiarized nondeprived male rats. However, in a food choice test where both novel and familiar food items were available, pregnanolone (1-3 mg/kg) significantly increased the time spent eating the novel food. These results suggest that unlike BZR agonists, which enhance feeding responses directly, pregnanolone may facilitate feeding secondarily via an attenuation of anxiety.

Animals↗