Adult personality and early experience.
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Biomedical subjects
Publications and source records attributed to J Kagan.
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We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14. 3. A portion of the DNA segment that spans this locus and is flanked by the microsatellite loci D13S153 and D13S163 was lost in 85% of the specimens with allele losses and was designated as a LOH cluster region (LCR). The LCR spans more than 6 Mbp of DNA. The results suggest that a TSG relevant for the development of prostate cancer is located telomeric to the RB locus. There was a significant correlation (P=0.0024) between chromosome 13q LOH and advanced metastatic disease, suggesting that loss of 13q14.3 region is associated with prostate cancer progression. However, further research must be conducted to establish the identity and function of this putative TSG.
This paper considers the influence of temperamental factors on the development of anxious symptoms in children and adolescents. About 20 percent of healthy children are born with a temperamental bias that predisposes them to be highly reactive to unfamiliar stimulation as infants and to be fearful of or avoidant to unfamiliar events and people as young children. Experiences act on this initial temperamental bias and, by adolescence, about one-third of this group is likely to show signs of serious social anxiety. These children are also likely to have one or more biological features, including a sympathetically more reactive cardiovascular system, asymmetry of cortical activation in EEG favoring a more active right frontal area, more power in the EEG in the higher frequency range, and a narrower facial skeleton. The data imply that this temperamental bias should be conceptualized as constraining the probability of developing a consistently fearless and spontaneous profile rather than as determining an anxious or introverted phenotype.
In recent years, the startle reflex has become an exciting new tool to investigate affective responses to aversive stimuli in humans. The popularity of this methodology is largely based on the substantial amount of animal research available on this topic. Several procedures have been developed to examine startle potentiation in humans, but most studies have been carried out in adults and may not be appropriate for children or adolescents. The present study is a multi-site project (Yale University, Harvard University, and the University of Minnesota) investigating two new procedures to examine the potentiation of startle in adolescents. The subjects were 50 male and female aged 13-17 years old. One procedure examined fear-potentiated startle to the threat of an unpleasant airblast directed to the larynx. The second examined the facilitation of startle in darkness. Potentiation was found using each procedure and the degree of potentiation was similar across laboratories. These results suggest that both the threat of an airblast and darkness can reliably be used to examine startle potentiation in young subjects.
A group of 164 children from different infant temperament categories were seen at 7 years of age for a laboratory battery that included behavioral and physiological measurements. The major results indicated that children who had been classified as high reactive infants at 4 months of age, compared with infants classified as low reactive, (a) were more vulnerable to the development of anxious symptoms at age 7 years, (b) were more subdued in their interactions with a female examiner, (c) made fewer errors on a task requiring inhibition of a reflex, and (d) were more reflective. Further, the high reactives who developed anxious symptoms differed from the high reactives without anxious symptoms with respect to fearful behavior in the second year and, at age 7 years, higher diastolic blood pressure, a narrower facial skeleton, and greater magnitude of cooling of the temperature of the fingertips to cognitive challenge. Finally, variation in magnitude of interference to fearful or aggressive pictures on a modified Stroop procedure failed to differentiate anxious from nonanxious or high from low reactive children.
We discuss selected psychological competences that develop and become noticeable between one and two years of age and are temporally correlated to structural, biochemical and physiological changes in the brain. The psychological competences are: Language development, a sense of "right" and "wrong", self-awareness, and the ability to make inferences. The accompanying changes in the brain involve the prefrontal cortex, language-related cortical areas, hippocampus, cerebellum, basal ganglia and an increase in the connectivity of the network. Of special interest are the maturational changes in layers III-IV of the prefrontal cortex. Layer III is the origin and target of callosal and commissural axons linking the two hemispheres and the target of associational axons linking ipsilateral areas within each hemisphere. Layer IV, the target for axons from the mediodorsal nucleus of the thalamus, conveys information from other associational cortices, cerebellum, basal ganglia, and the reticular and limbic systems. In the second year, intensive dendritic growth and synaptogenesis in these layers increase the linking of these two layers and form a neural basis for a more efficient convergence and integration of information from the two hemispheres, which are functionally asymmetric. It is our hypothesis that these changes, together with the maturational changes in the cortico-subcortical network, are a basis for the observed emergence of the psychological competences. We are aware that temporal correlations cannot prove firm causal relationships. However, knowledge of these correlations is useful in generating specific hypotheses that can be tested directly.
OBJECTIVE: To determine whether children at risk for the development of adult alcohol dependence would show greater "behavioral inhibition" to the unfamiliar, an early childhood temperament characteristic. METHOD: One hundred peer play evaluations were conducted blindly with preschool children from families selected to be at high or low risk for developing alcohol dependence. Each child was paired with different children (same-sex pairs) in independent sessions to determine the stability of the behavioral response. RESULTS: High-risk children spent significantly more time staring at the other child during the peer play session while refraining from engaging in play, and significantly less time speaking to the other child. Significantly more time was spent proximal to the parent, but only on the first peer play session. These behaviors have been shown to be indicators of behavioral inhibition. CONCLUSIONS: These findings suggest that the presence of behavioral inhibition to the unfamiliar in childhood may be a risk factor for later development of alcohol dependence. While there is abundant evidence that childhood externalizing behaviors are risk factors for later development of substance dependence, the present results suggest that internalizing behaviors may be a pathway as well.
OBJECTIVE: Chess and Thomas suggested that temperament might make a contribution to social phobia and other forms of extreme social anxiety. This study provides the first investigation of the outcomes in adolescents who had been inhibited (subdued to and avoidant of novelty) or uninhibited (approaching novelty) in the second year of life, utilizing both direct interview and direct observation. METHOD: Seventy-nine subjects, aged 13 years, who had been classified as inhibited or uninhibited in the second year were assessed with both standardized interview and direct observation. RESULTS: There was a significant association between earlier classification of a child as inhibited and generalized social anxiety at adolescence, but no association with specific fears, separation anxiety, or performance anxiety. The adolescents who were classified as socially anxious made fewer spontaneous comments than those without social anxiety; no relation was seen between any other type of fear and the number of spontaneous comments. Adolescent girls who had been inhibited as toddlers were more likely to be impaired by generalized social anxiety than boys. CONCLUSIONS: The interview and observational data indicate that important aspects of an inhibited temperament are preserved from the second year of life to early adolescence, which predispose an adolescent to social anxiety.
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This article reviews the three major ways parents influence children: direct interaction, identification, and transmission of family stories. This essay summarizes some of the relevant empiric data in support of this claim and describes the operation of other mechanisms that also contribute to the child's development.
We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions and in 67% of the invasive carcinomas. The highest frequency of allele losses in dysplasia (20% and 17%), and invasive carcinoma (40% and 48%) were detected in the same D8S298 and LPL-tet loci located on chromosomes 8p21 and 8p22 respectively. The minimal region with LOH was limited to 4.6 megaBases (mBs) at 8p22 and 7.1 mBs at 8p21. In addition, allelic losses in both dysplastic and corresponding invasive specimens were noted at the same loci in some tumors suggesting their emergence from a common preneoplastic clone. Allele losses correlated significantly with male gender, oral and laryngeal sites and high proliferative index. The data suggest that inactivation of tumor suppressor gene(s), within these loci, may constitute an early event in the evolution of oral and laryngeal SC.
A limited number of previous studies have indicated a low frequency of chromosome 10 allele losses and deletions in bladder cancers. We investigated the involvement of chromosome 10 in advanced bladder cancers. Loss of heterozygosity (LOH) was analysed in 19 microsatellite loci in 20 grade III invasive transitional cell carcinomas. Nine (45%) of the 20 tumors had at least one allele loss on the long arm of chromosome 10. The short arm of chromosome 10 was not affected. The most frequent LOH occurred at D10S215, where four (29%) of 14 of the informative cases had an allele loss. The minimal region with allele losses was located between the centromeric marker D10S1644 and the telomeric marker D10S541, which are separated by 2.52 cM. The results strongly suggest the existence within that region of a tumor suppressor gene or genes for advanced bladder cancer.
A group of 193 children, classified as high or low reactive to stimulation at 4 months and observed again at 14 and 21 months, were observed at 4 1/2 years of age for behavioral signs of inhibited or uninhibited behavior. Children who had been high reactive were less spontaneous and less sociable than those who had been classified as low reactive, but only a small proportion of children maintained a consistently inhibited or uninhibited phenotype at all ages.
We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8+ cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically. In the first 2 weeks, CD4 counts increased for all subjects and plasma viremia decreased in five of six subjects. Twenty-four weeks later, the mean values of all measures of viral burden and surrogate markers of HIV infection were either unchanged or improved, but none of the changes was statistically significant. Two subjects continued to have decreased cell-associated viral burden and another subject had more than doubled CD4 cell count. HIV-specific CTL activity increased in most subjects. The increase in CD4 T-cell counts in the first weeks after the infusion suggests that antiviral CTLs of diverse specificities do not play a significant role in CD4 T-cell decline. The lack of any acute toxicity or adverse effect on viral burden suggests that therapy with antiviral CTLs deserves further study.
OBJECTIVE: To explore how gender and social class affect perceptions of health status among 16-year-old adolescents. DESIGN: Cross-sectional survey. SETTING: University psychology laboratory. PARTICIPANS: Fifty upper-middle-class and 48 working-class adolescents stratified by gender. MAIN OUTCOME MEASURES: The general health perceptions (GHP) scale of the Medical Outcomes Survey 36-Item Short Form Health Survey (SF-36). The other self-reported health status domains and 3 measures of different aspects of psychological well-being were included as covariates in analysis of variance models. RESULTS: Upper-middle-class females reported the lowest and upper-middle-class males the highest GHP (76.7 vs 88.4, P=.003). A multivariate regression model (adjusted R2=0.08) revealed significant gender (P=.03) differences in GHP, but not a social class effect, and an interaction effect between gender and class (P=.01). With addition of psychological well-being covariates (P<.001), gender remained significant (P=.04) and a significant portion of the interaction effect (P=.13) was explained. When the self-reported physical health status scales (P<.001) were added to the model (adjusted R2=0.51), gender remained significant (P=.03) and the interaction effect was partially explained (P=.07). CONCLUSIONS: Gender is a crucial factor in understanding the complex relationships between sociostructural inequalities and health differentials. These data suggest that psychological well-being and self-reported physical health status mediate the effects of gender and the gender and social class interaction in explaining variation in GHP. Contrary to the social class gradient hypothesis, upper-middle-class females reported the lowest GHP. These results suggest that the paradigms applicable to early childhood and adulthood may not be appropriate to understand the complex dynamics of adolescence.
7-Methylpyrido[3,4-c]psoralen has recently been found to photosensitize the crosslinking and cleavage of double-stranded pBR322 DNA (4361 bp) with an unusual degree of site specificity. Following cleavage of the photosensitized pBR322 with the restriction enzymes Pvu II and BamH I, the main fragments were analyzed electrophoretically. Only three possible cleavage areas on the plasmid were suggested by this analysis. They were within the ranges bounded by the positions 801-926, 3172-3303 and 4226-4310. The sensitizer also induced selective cleavage in the related plasmid pUC19 (2686 bp), but the pattern was somewhat more complicated and was not analyzed in detail.
This paper examines critically four habits of social scientists: a reliance on constructs for processes that do not specify the class of agent or the context of action, skepticism toward empirical truths that are inconsistent with political or social goals, a reluctance to use profiles or characteristics that have different weights to classify persons, and an aversion to treating subjects with extreme values as representing special categories. These points are made in the context of the author's research on temperaments in children.