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G Carey

Publications and source records attributed to G Carey.

At least 19 recordsLinked to original sources
PubMed2000

The dopamine D(1) receptor agonist SKF-82958 serves as a discriminative stimulus in the rat.

We examined the discriminative stimulus effects of the high-efficacy dopamine D(1) receptor agonist (+/-)6-chloro-7, 8-dihydroxy-3-ally1-phenyl-2,3,4,5-tetrahydro-1H-3benzazepine++ + hydrobromide (SKF-82958) in rats trained to discriminate SKF-82958 (0.03 mg/kg) from vehicle in a two-lever food-reinforced drug discrimination task. SKF-82958 produced dose-related increases in responding to the SKF-82958 appropriate lever with full substitution occurring at the training dose. Pretreatment with the dopamine D(1)/D(5) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2hydroxy-N-methyl-5H-benzo-[d]naphtho -¿2, 1-b¿azepine (SCH-39166) (0.01 mg/kg) attenuated the discriminative stimulus effects of SKF-82958. Pretreatment with the dopamine D(2) receptor antagonist raclopride (0.03 mg/kg) had no effect. The high-efficacy dopamine D(1) receptor agonist R(+)6chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297) fully substituted for SKF-82958, whereas the low-efficacy dopamine D(1) receptor agonist (+/-)1-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF-38393) produced only partial substitution. The dopamine D(2) receptor agonist trans-(+/-)-4,4a,5,6,7,8,8a, 9-octahydro-5-propyl-1H-propyl-1H-pyrazolo[3,4-g]quinoline dihydrochloride (quinpirole) and the indirect dopamine agonist cocaine did not substitute fully for the SKF-82958 discriminative stimulus cue. These results demonstrate that the high-efficacy dopamine D(1) receptor agonist SKF-82958 can serve as an effective discriminative stimulus in the rat, and that these effects are mediated by a dopamine D(1)-like receptor mechanism.

Animals↗
PubMed1999

Heritability of MMPI Harris-Lingoes and Subtle-Obvious subscales in twins reared apart.

A large sample of identical and fraternal twins who had been reared apart was used to examine the genetic and environmental architecture of the MMPI Subtle-Obvious and Harris-Lingoes subscales. Univariate genetic analyses indicated significant heritability for all 28 of the Harris-Lingoes subscales (estimates ranged from.23 to.61), all five Obvious subscales (estimates ranged from.37 to.56) and four of the five Subtle subscales (estimates ranged from.27 to.35). Two randomly constructed scales were analyzed as controls; neither of these scales showed significant heritability. Exploratory correlational findings suggested that three of the Wiener-Harmon Subtle subscales may tap aspects of psychological health, naivete, or repression. Ma-S may come closest to Wiener and Harmon s intent. Although they apparently diverge from their original purpose, it may be too early to abandon the low face valid items of the Subtle subscales.

Adolescent↗
PubMed1998

p53 overexpression and downregulation of inter-alpha-inhibitor are associated with hyaluronidase enhancement of TNF cytotoxicity in L929 fibroblasts.

Degradation of extracellular matrix by hyaluronidase increases murine L929 cell sensitivity to tumor necrosis factor (TNF) cytotoxicity. Seeding and culturing L929 cells onto the matrix of serum fetuin and the hyaluronate-binding inter-alpha-inhibitor resulted in inhibition of hyaluronidase-enhanced TNF killing, suggesting that the release of these proteins from hyaluronidase-degraded matrix confers cellular TNF susceptibility. Metabolic labeling studies showed that hyaluronidase mediated de novo protein synthesis and down regulated several proteins in L929 cells. Specifically, hyaluronidase upregulated p53 protein expression (>200%) but down regulated a p85 inter-alpha-inhibitor-like protein (>90%) in L929 cells, whereas it had no effect on the protein levels of ICH-1, Bcl-xL, Bcl-2, Fas ligand, CAS (cellular apoptosis susceptible protein), TIAR (an RNA-binding protein) and alpha-tubulin. Conceivably, hyaluronidase enhancement of TNF sensitivity in L929 cells is p53-dependent and the matrix inter-alpha-inhibitor contributes a protective role against TNF cytotoxicity.

Alpha-Globulins↗
PubMed1998

Antisocial behavior, substance use, and somatization in families of adolescent drug abusers and adolescent controls.

Symptoms of conduct disorder (CD), antisocial personality disorder (ASP), alcohol abuse, drug abuse, and somatization were tabulated for the families of 35 delinquent, substance-abusing (multiple-problem) adolescent male probands and 35 age-matched control males. Alcohol abuse, CD/ASP, and somatization were assessed with either the Diagnostic Interview Schedule (DIS) (for participants aged 18 and up) or the Diagnostic Interview for Children and Adolescents (DICA) (for participants aged 12 to 17). Drug abuse for all participants was assessed with the Substance Abuse Module (SAM) of the Comprehensive Interview for Diagnostic Evaluation (CIDE). As expected, proband groups had significantly more (p < .0001) CD/ASP, alcohol abuse, and drug abuse symptoms than control groups. A significant (p < .01) positive correlation among CD/ASP, alcohol abuse, and drug abuse was found for each group. Somatization was not differentially associated with proband status. It was concluded that identifying male multiple-problem youths also identifies families with a high incidence of similar problems.

Adolescent↗
PubMed1997

Characterization of an insulin-like growth factor (IGF) receptor and the insulin-like effects of IGF-1 in the bony fish, Lates calcarifer.

The present work is part of a broad phylogenetic study of the insulin superfamily of peptides in lower vertebrates. In the bony fish barramundi (Lates calcarifer), the presence of IGF receptors were investigated in the liver by means of competitive binding studies. The results suggested the presence of a type 1-like but no type 2-like IGF receptor. We also demonstrated insulin-like effects of intraperitoneally injected recombinant human (rh)-IGF-1 in barramundi with rh-IGF-1 and rh-insulin showing similar effects with respect to induction of hypoglycemia and stimulation of incorporation of [14C]-glucose into muscle glycogen.

Animals↗
PubMed1997

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: a review of its behavioural properties.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.c.). It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse (ID50 = 4.4 mg kg-1 i.p.). JL13, like clozapine, was able to antagonize (+/-)-DOI-induced head-twitches in the mouse (ID50 = 2.0 mg kg-1 i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1 i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3-10 mg kg-1 i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Animals↗
PubMed1997

Genetic and environmental architecture of human aggression.

A meta-analysis was performed on data from 24 genetically informative studies by using various personality measures of aggression. There was a strong overall genetic effect that may account for up to 50% of the variance in aggression. This effect was not attributed to methodological inadequacies in the twin or adoption designs. Age differences were important. Self-report and parental ratings showed genes and the family environment to be important in youth; the influence of genes increased but that of family environment decreased at later ages. Observational ratings of laboratory behavior found no evidence for heritability and a very strong family environment effect. Given that almost all substantive conclusions about the genetics of personality have been drawn from self or parental reports, this last finding has obvious and important implications for both aggression research in particular and personality research.

Adolescent↗
PubMed1996

Heritability of MMPI personality indicators of psychopathology in twins reared apart.

This report presents Minnesota Multiphasic Personality Inventory (MMPI) findings from the Minnesota Study of Twins Reared Apart. Data from 65 unique pairs of monozygotic twins reared apart (MZA) and 54 unique pairs of dizygotic twins reared apart (DZA) were analyzed. As in other results from this sample, MZA twins evidenced substantial similarity, highlighting the influence of shared genes. Biometric modeling yielded estimates of heritability for the MMPI's standard validity and clinical scales and for the Wiggins content scales ranging from .26 to .62 (M = .44), echoing previous findings from the twin and adoption literature on personality. The pattern of MZA and DZA correlations suggested nonadditive genetic effects for 3 MMPI scales. Multivariate profile analyses also suggested genetic influence on both profile elevation and shape.

Adolescent↗
PubMed1995

The incidence of antibody formation to OKT3 consequent to its use in organ transplantation.

Enzyme-linked immunosorbent assays were performed on 12,133 serum samples to determine the incidence of anti-OKT3 antibody formation among transplant recipients who had received OKT3 for rejection treatment or prophylaxis. High anti-OKT3 antibody titers (> or = 1:1000) were detected in 5.8% of samples drawn 2 to 8 weeks following initiation of OKT3 therapy. The frequency of high titers differed by organ (6.9%, 2.7%, and 5.3% for kidney, heart, and liver, respectively; P < 0.001) and by sampling times (P < 0.001). The highest frequency of positive titers was obtained in samples obtained between 2 and 4 weeks following the initiation of OKT3. For all transplant recipients and for kidney recipients alone, multivariate logistic regression showed that the risk of high anti-OKT3 titers varied significantly at 2 to 4 weeks and at 4 to 6 weeks (but not at 6 to 8 weeks) with age (the youngest patients had the highest incidence, with a steady decline after age 30; P < 0.05), course of therapy (lowest frequencies followed a first course of OKT3; P < 0.001), and transplant number (lowest frequencies followed a first transplant; P < 0.01). Analyses of a set of patients on whom immunosuppressive regimen information was available indicated that prophylactic or maintenance treatment with CsA was associated with a significantly lower frequency of high-titer anti-OKT3 antibodies than was therapy without CsA (P < 0.001). In conclusion, this series provides confirming evidence that high-titer anti-OKT3 antibodies, which are of concern whenever retreatment with OKT3 is contemplated, occur in a low percentage of patients and are associated with such factors as age, previous transplantation or courses of therapy with OKT3, and treatment with CsA.

Adolescent↗
PubMed1995

A twin study of non-alcohol substance abuse.

Except for alcohol abuse, little is known about the familial aggregation for substance abuse. Here we report twin resemblance for non-alcohol substance use in the Washington University Twin Series, wherein probands were identified by consecutive admission to psychiatric facilities in the St. Louis area. A 5-point substance abuse scale was constructed with values anchored by never used drugs (1) to drug dependence (5). Year of birth was the most powerful predictor of drug use--younger twins scored far higher than older twins. Either heritability or common environment had to be included in the regression model to avoid a significant drop in explained variance, but which was more important could not be resolved. The correlation for identical twins exceeded that for fraternal twins, suggesting the possibility of a heritable factor.

Adolescent↗
PubMed1994

Genetic association study in psychiatry: analytical evaluation and a recommendation.

Recent analysis of the candidate gene, association study for psychiatric disorders have concluded that most statistically significant results are likely to be false positives because there are a large number of potential candidate loci and a low a priori probability that a given candidate locus will in fact be trait relevant. Hence, it was recommended that the alpha level (P level) be lowered for association studies. The present study demonstrates that lowering the alpha level to some fixed, predetermined value is not a recommended strategy. Rather, the probability of false positives (and false negatives) depends on such parameters as the prevalence of the disorder, the prevalence of the genotypes at the candidate locus, and the relative risk. In some areas of the parameter space, the adjustment to alpha may be modest. In other areas, however, even the requirement of one or more independent replications of the original results gives false positive rates exceeding 80% or 90%. Hence, the P levels required to minimize false positives may have to be changed from one statistical test to another even within the same study. A procedure for adjusting the probability level for a test of association between genotypes and a disorder is given.

False Negative Reactions↗
PubMed1994

Personality and psychopathology: genetic perspectives.

Genetic factors exert an important influence on adult personality traits, accounting for anywhere between 30% and 60% of the variance. Heredity is also important for most forms of psychopathology and plays a major role in several theories that relate personality to psychopathology. Despite this, there has been surprisingly little multivariate genetic research reported on joint analyses of personality and psychopathology. The small amount of available data suggests that genes may account for over 50% of the observed correlation between neuroticism and state symptoms of anxiety and depression. The mechanisms behind such strong genetic correlations are crucial for understanding the causal relationship between a personality trait and a disorder because genetically influenced biological systems may operate as exogenous "third-party" factors that are responsible for what appear to be phenotypic cause-effect relationships. We illustrate how recent analytical advances in behavior genetics can use multivariate family data to address questions about the causal role of personality in psychopathology.

Diseases in Twins↗
PubMed1993

Path analysis and sib-pair linkage.

When the distance between linked loci is expressed in terms of the correlation between the identity-by-descent (idb) values of the loci, then a path model may be used to order loci with data on sib-pairs and their parents. The relationship between the recombination fraction and the correlation coefficient is developed and a method for fitting a covariance matrix predicted by a specific ordering of loci to an observed covariance matrix is proposed.

Epidemiologic Methods↗
PubMed1992

Simulated twin data on substance abuse.

Twin data were simulated for use of a new illegal substance. The twin cohort was "measured" yearly at 10 time intervals during the diffusion of the substance throughout the nation. The models used to generate the data are discussed.

Adolescent↗
PubMed1992

Twin imitation for antisocial behavior: implications for genetic and family environment research.

When twin pairs influence each other's behavior, observed variance is greater for MZ twins than for DZ twins under at least 1 of 2 conditions: (a) the trait has some heritability and (b) MZ twins influence each other more than do DZ twins. Applied to a trait that has an underlying continuous distribution but is measured as a dichotomy, the presence of reciprocal twin influence predicts that if the base rate for the trait is not exactly 50%, then the prevalence of the trait should differ in MZ and DZ twin pairs. This prediction held for registered criminality in a large twin cohort. Methods of analysis that permit reciprocal twin interaction not only provide better statistical fits to the data but also yield estimates of heritability that agree with adoption data. The results suggest that the genetic influence on registered criminality may be more modest than previously thought.

Antisocial Personality Disorder↗