PubMed Health⌕ Search

Biomedical subjects

J Kagan

Publications and source records attributed to J Kagan.

At least 19 recordsLinked to original sources
PubMed1999

Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study.

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.

Adolescent↗
PubMed1999

Behavioral inhibition in children from families at high risk for developing alcoholism.

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.

Adult↗
PubMed1999

Adolescent social anxiety as an outcome of inhibited temperament in childhood.

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.

Adolescent↗
PubMed1999

The role of parents in children's psychological development.

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.

Child↗
PubMed1998

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma.

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.

Adult↗
PubMed1998

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer.

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.

Aged↗
PubMed1998

Childhood derivatives of high and low reactivity in infancy.

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.

Age Factors↗
PubMed1997

Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients.

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.

Amino Acid Sequence↗
PubMed1997

Influences of gender and social class on adolescents' perceptions of health.

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.

Adolescent↗
PubMed1997

Sites of preferred interaction between double-stranded pBR322 DNA and 7-methylpyrido[3,4-c]psoralen.

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.

Binding Sites↗
PubMed1997

Conceptualizing psychopathology: the importance of developmental profiles.

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.

Adaptation, Psychological↗
PubMed1997

Neurobiological bases of behavioral development in the first year.

This review summarizes the temporal relations between selected psychological milestones in the first year of the human infant and theoretically relevant developmental neurobiological changes in the brain, supplemented where appropriate, with evidence from the non-human primate. The disappearance of the palmar grasp reflex and the decrease in endogenous smiling and spontaneous crying, which occur at 2-3 months, are correlated to emergent cortical inhibition of brainstem circuits. In addition, the improved ability to recognize an event experienced in the immediate past (recognition memory) is related to growth of the hippocampus and adjacent structures at this age. The behavioral developments at 7-10 months include an enhanced ability to retrieve stored representations of the past and to compare past and present (working memory), along with the emergence of the universal fears of strangers and separation from the caretaker. These milestones are correlated in time with maturational changes in the prefrontal and rhinal cortices and hippocampal formation, the integration of the limbic system and increased responsiveness of the hypothalamus-pituitary-adrenal axis. Knowledge of age-dependent correlations of brain and behavioral maturation is a basis for the investigation of causal relationships between brain development and behavior. A close collaboration of pediatricians, psychologists and neuroscientists is, therefore, necessary.

Age Factors↗
PubMed1997

An approach to the validation of markers for use in AIDS clinical trials.

Dr. Mildvan and coauthors have thoroughly reviewed and documented what is known about the validation of surrogate markers for use in clinical trials. They have proposed a classification system based on the usefulness of available immunologic and virological assays as measures of prognosis, drug activity, and therapeutic efficacy. The latter, a type II marker in the proposed classification, should estimate the proportion of treatment effect explained by change in the marker induced by therapy and, if complete, can substitute for clinical endpoints. HIV clinical trialists have had a long-standing interest in using surrogates for clinical endpoints to facilitate conduct of experimental protocols and to decrease the time and effort required to develop new treatment strategies. The approach outlined in this review by experienced clinicians, biostatisticians, and immunologists provides a framework to evaluate currently available and potential surrogate markers.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications.

Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.

Adenoma↗
PubMed1997

Photochemical and photobiological studies of a furonaphthopyranone as a benzo-spaced psoralen analog in cell-free and cellular DNA.

Photobiological activities of the benzo-spaced psoralen analog furonaphthopyranone 3 have been investigated in cell-free and cellular DNA. The molecular geometry parameters of 3 suggest that it should not form interstrand crosslinks with DNA. With cell-free DNA no evidence for crosslinking but also not for monoadduct formation was obtained; rather, the unnatural furocoumarin 3 induces oxidative DNA modifications under near-UVA irradiation. The enzymatic assay of the photosensitized damage in cell-free PM2 DNA revealed the significant formation of lesions sensitive to formamidopyrimidine DNA glycosylase (Fpg protein). In the photooxidation of calf thymus DNA by the furonaphthopyranone 3, 0.29 +/- 0.02% 8-oxo-7,8-dihydroguanine (8-oxoGua) was observed. With 2'-deoxyguanosine (dGuo), the guanidine-releasing photooxidation products oxazolone and oxoimidazolidine were formed predominately, while 8-oxodGuo and 4-HO-8-oxodGuo were obtained in minor amounts. The lack of a significant D2O effect in the photooxidation of DNA and dGuo reveals that singlet oxygen (type II process) plays a minor role; control experiments with tert-butanol and mannitol confirm the absence of hydroxyl radicals as oxidizing species. The furonaphthopyranone 3 (Ered = -1.93 +/- 0.03V) should act in its singlet-excited state as electron acceptor for the photooxidation of dGuo (delta GET ca -6 kcal/mol), which corroborates photoinduced electron transfer (type I) as a major DNA-oxidizing mechanism. A comet assay in Chinese hamster ovary (CHO) AS52 cells demonstrated that the psoralen analog 3 damages cellular DNA upon near-UVA irradiation; however, no photosensitized mutagenicity was observed in CHO AS52 cell cultures.

Animals↗
PubMed1997

Temperament and the reactions to unfamiliarity.

The behavioral reactions to unfamiliar events are basic phenomena in all vertebrates. Four-month-old infants who show a low threshold to become distressed and motorically aroused to unfamiliar stimuli are more likely than others to become fearful and subdued during early childhood, whereas infants who show a high arousal threshold are more likely to become bold and sociable. After presenting some developmental correlates and trajectories of these 2 temperamental biases, I consider their implications for psychopathology and the relation between propositions containing psychological and biological concepts.

Anxiety Disorders↗
PubMed1997

Daylength during pregnancy and shyness in children: results from northern and southern hemispheres.

An extreme degree of shyness in young children is a temperamental trait under modest genetic influence and characterized by distinct physiological profiles. Data from both the United States and New Zealand indicate that maternal exposure to short daylength during pregnancy, especially the midpoint of gestation, predicts an increased risk of subsequent shy behavior in children. Estimates of attributable risk indicate that approximately one-quarter of shyness prevalence can be linked to pregnancy during times of reduced daylength. This phenomenon might be mediated by changing concentrations of melatonin, serotonin, or other neurotransmitters or corticoids that are known to covary with seasonal variations in daylength.

Child↗