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Biomedical subjects

J Kagan

Publications and source records attributed to J Kagan.

At least 91 records · Page 5Linked to original sources
PubMed1992

Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children.

OBJECTIVE: Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders. However, the factors determining which inhibited children were at risk for childhood onset of anxiety disorders remained unknown. The authors of this study hypothesized that greater anxiety loading in parents would increase the risk for anxiety disorders in children with behavioral inhibition. METHOD: Using DSM-III structured interviews, the authors examined patterns of aggregation of anxiety disorders in parents of two existing cohorts of children, one cross-sectional and clinically derived (31 children, 60 parents) and the other epidemiologically derived and longitudinal (40 children, 75 parents). Within each cohort, parents were stratified into three groups based on the presence (behavioral inhibition and anxiety) or absence (behavioral inhibition only, no behavioral inhibition and no anxiety) of behavioral inhibition and two or more anxiety disorders in their child. RESULTS: Parents of children with behavioral inhibition and anxiety, from both the clinical and nonclinical cohorts, had significantly higher rates of two or more anxiety disorders than did parents of children with behavioral inhibition only and parents of children with no behavioral inhibition and no anxiety. CONCLUSIONS: These results indicate that the presence of parental loading for anxiety disorders may help to identify the subgroup of inhibited children at very high risk for developing childhood-onset anxiety disorders.

Adult↗
PubMed1992

Temperament, emotion, and cognition at fourteen months: the MacArthur Longitudinal Twin Study.

200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin correlations suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotions was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament.

Cognition↗
PubMed1991

Further evidence of an association between behavioral inhibition and anxiety disorders: results from a family study of children from a non-clinical sample.

Behavioral inhibition to the unfamiliar, identifiable in early childhood and reflecting the tendency to exhibit withdrawal and excessive autonomic arousal to challenge or novelty, has been found to be prevalent in young offspring of parents with panic disorder and agoraphobia and associated with risk for anxiety disorders in these children. Using family study methodology, we now examine psychopathology in first degree relatives of children from a non-clinical longitudinal cohort identified at 21 months of age as inhibited (N = 22) or uninhibited (N = 19) and followed through the age of seven years for a study of preservation of temperamental characteristics in normal children. These assessments were compared with evaluations of the first degree relatives of 20 normal comparison children. Psychiatric assessments of parents (N = 110) and siblings (N = 72) were based on structured interviews conducted blindly to the temperamental classification of the index child. Parents of inhibited children, compared with parents of uninhibited and normal controls, had significantly higher risks for multiple (greater than or equal to 2) anxiety disorders, continuing anxiety disorders (both a childhood and adulthood anxiety disorder in the same parent), social phobia, and childhood avoidant and overanxious disorders. These findings provide additional support for the hypothesis linking behavioral inhibition with risk for anxiety disorder.

Adolescent↗
PubMed1991

Temperamental factors in human development.

The initial dispositions to approach or to avoid unfamiliar events are 2 temperamental characteristics of children--among the many that have been described--that appear to be moderately stable over time and associated with distinct, physiological profiles that may be under partial genetic control. The display of high versus low levels of both motor activity and crying to unfamiliar in 4-month-old infants predicts these 2 temperamental profiles in the 2nd year. This fact implies, but does not prove, that variation in the excitability of those brain areas that mediate motor activity and crying participates in the actualization of the temperamental categories called inhibited and uninhibited to the unfamiliar.

Arousal↗
PubMed1991

alpha-Terthienyl photosensitizes damage to pBR322 DNA.

alpha-Terthienyl photosensitizes single strand breaks in pBR322 DNA. Almost identical results were observed under oxygen and under argon. In the presence of oxygen, this DNA nicking was enhanced by histidine and was not affected by superoxide dismutase, catalase, or the antioxidant BHT. Although chemical damage to DNA treated with alpha-terthienyl plus near-UV was clearly demonstrated in vitro, transformation in E. coli with this damaged pBR322 DNA still took place. Likewise, Haemophilus influenzae DNA transforming activity was not significantly decreased by photosensitization with alpha-terthienyl.

DNA Damage↗
PubMed1991

Depression and allergies: survey of a nonclinical population.

The possible association between depression and type I allergies (i.e. immunoglobulin E-mediated hay fever, asthma, eczema, hives) was examined in a nonclinical sample of 379 college students. Measures included self-reports of depression, tiredness, fearfulness, allergic disorders, and environmental allergens and irritants. Seventy-one percent of the subjects who had ever received a professional diagnosis of depression also indicated a history of allergy: those with greater self-rated current depression overall reported a significantly higher prevalence of asthma (p less than 0.05). Type I allergic (43%) and nonallergic subjects did not differ in self-rated frequency of depression, fatigue, or anxiety. However, type I subjects reported significantly worse mood after the flu than did nonallergic subjects (p less than 0.001). The data support the hypothesis that individuals prone to clinical depression have more allergies than nondepressives. Allergics may experience more postflu mood worsening but not current depression in comparison with nonallergics.

Adult↗
PubMed1991

Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis.

The primary structure of the human substance K receptor was established from the sequences of complementary DNA clones isolated from a human jejunal complementary DNA library. It consists of 398 amino acids, including seven putative transmembrane regions. The gene for the human substance K receptor was localized to chromosome region 10p13-10q23, a region with frequent chromosomal abnormalities. The human substance K receptor was expressed in transfected NIH-3T3 cells lacking endogenous substance K receptors, and Scatchard analysis of 125I-labeled substance K binding indicates approximately 100,000 receptors/cell with a single dissociation constant of 12 nM. Covalent cross-linking experiments utilizing 125I-substance K and three different chemical cross-linking reagents (disuccinimidyl suberate, disuccinimidyl tartrate, or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl) demonstrate an apparent molecular weight of 45,000, consistent with little or no N-linked glycosylation. The binding of substance K to its receptor on transfected cells led to a rapid increase in the production of total inositol phosphates and the release of Ca2+ from internal stores. Growth of the cells transfected with the human substance K receptor is stimulated by the addition of substance K to the medium to a level similar to 10% serum. Therefore, the human substance K receptor can function as a growth factor receptor when expressed in mouse 3T3 cells.

Amino Acid Sequence↗
PubMed1990

Interleukin 6 is essential for antibody secretion by human in vivo antigen-induced lymphoblastoid B cells.

In vivo immunization of normal subjects with a variety of antigens generates circulating lymphoblastoid (LB) B cells, which in vitro spontaneously secrete significant levels of specific antibody. Since activation and initial differentiation of these cells occurs in vivo, they provide a useful model for the study of the later stages of B cell maturation. In the present study, we investigated the requirement of interleukin 6 (IL-6) for the "spontaneous" in vitro production of IgG-Tet by LB B cells. Addition of IL-6 to cultures of LB B cells in medium supplemented with 10% fetal calf serum failed to increase the levels of IgG-Tet produced in vitro. However, addition of anti-IL-6 antibodies decreased IgG-Tet production as much as 70%, and this inhibition could be reversed by the addition of IL-6. LB B cells cultured in serum-free medium in order to restrict endogenous IL-6 production secreted only low levels of antibody, unless exogenous IL-6 was added. Addition of 2.5 units/ml of IL-6 to serum-free cultures induced an increase in IgG-Tet secretion nearly comparable to that seen in cultures supplied with serum. The magnitude of the increase in IgG-Tet secretion in response to exogenous IL-6 was inversely related to the number of cells in culture, which was due in part to increased endogenous IL-6 production in cultures with higher cell concentrations. Experiments including hydroxyurea in serum-free cultures indicated that IL-6-dependent enhancement of LB B cells' IgG-Tet secretion was not primarily mediated by cell growth. These observations suggest that in vivo generated LB B cells are not totally committed to antibody secretion, and that IL-6 is essential for in vivo antigen-induced LB B cells to reach the antibody-secreting stage.

Antibodies↗
PubMed1990

Rearrangements in the human T-cell-receptor alpha-chain locus in patients with adult T-cell leukemia carrying translocations involving chromosome 14q11.

We describe 5 cases of adult T-cell leukemia (ATL) carrying translocations at chromosome 14q11, where the genes for alpha- and delta-chains of the T-cell receptor (TCR alpha/delta) reside (Croce et al., 1985; Isobe et al., 1988). Since the TCR alpha/delta locus is the region where several types of chromosome translocations occur in T-cell tumors, rearrangements of the TCR alpha/delta locus in those ATL cases were studied as a first step to characterize these translocations at the molecular level. For this purpose we have generated an extensive series of probes to define the specificity and the diversity of rearrangement occurring at the widely spanned J alpha-C alpha locus and the complex D delta-J delta-C delta-V delta 2 locus. Using a set of probes, we have found the deletion of the TCR delta locus in all ATL cases, and at least 2 rearrangements in the J delta locus in each case of ATL. It is possible that translocations in the TCR alpha locus may be involved in ATL.

Chromosome Mapping↗
PubMed1990

The human fibroblast adenine nucleotide translocator gene. Molecular cloning and sequence.

The human adenine nucleotide translocator multigene family consists of three transcribed genes and at least seven pseudogenes. We report the cloning and sequencing of the gene expressed in human fibroblasts. Like the other two transcribed genes, it has four exons. The 5'-flanking region of the fibroblast translocase gene contains a functional promoter. The promoter has a TATA motif beginning 30 base pairs upstream of the transcription initiation site and five potential SP1 binding sites, but lacks a canonical CCAAT box immediately upstream of the TATA sequence. Differences among the sequence motifs of the 5'-flanking region of the three human translocase genes could account for differences in their cell type-specific and proliferation-associated expression.

Base Sequence↗
PubMed1990

Detection of minimal residual disease in leukemic patients with the t(10;14)(q24;q11) chromosomal translocation.

Early relapse and minimal residual disease during clinical remission was examined in two patients having acute T-cell leukemia/lymphoma with the t(10;14)(q24;q11) chromosomal translocation. Molecular probes which can detect T-cell receptor alpha/delta clonal rearrangements and a TCL-3 probe which can detect the clonal rearrangement due to the chromosomal translocation failed to detect the leukemic clones during clinical remission by Southern filter hybridization. However, application of the polymerase chain reaction technology in amplification of the t(10;14)(q24;q11) chromosomal juncture during clinical remission permitted us to increase the detection level of neoplastic cells up to 1 leukemic cell/125,000 normal cells using 1 microgram of DNA. Amplified junction fragments were detected in both patients. In one case, during the period of clinical remission no amplified fragments were detected.

Base Sequence↗
PubMed1990

Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids.

T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.

Alleles↗
PubMed1990

Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders.

Behavioral inhibition is a laboratory-based temperamental category by the tendency to constrict behavior in unfamiliar situations and assumed to reflect low thresholds of limbic arousal. We previously found behavioral inhibition prevalent in the offspring of parents with panic disorder and agoraphobia. In this report, we examined the psychiatric correlates of behavioral inhibition by evaluating the sample of offspring of parents with panic disorder and agoraphobia, previously dichotomized as inhibited and not inhibited, and an existing epidemiologically derived sample of children, followed by Kagan and colleagues and originally identified at 21 months of age as inhibited or uninhibited. A third group of healthy children was added for comparison. Our findings indicate that inhibited children had increased risk for multiple anxiety, overanxious, and phobic disorders. It is suggested that behavioral inhibition may be associated with risk for anxiety disorders in children.

Agoraphobia↗