Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas.

Twenty-two new HLA-A2.1-binding peptides derived from the protooncogene HER2/neu were identified and analyzed for their capacity to elicit peptide and tumor-specific CTL responses. We used peptide-pulsed autologous DC from the ascites of patients with ovarian carcinomas to induce CTL.

Tobacco, alcohol and drug use in eight- to sixteen-year-old twins: the Virginia Twin Study of Adolescent Behavioral Development.

Objective: This study reports prevalences of lifetime and current alcohol, tobacco and drug use in adolescents; examines associations between substance use and a number of putative risk factors; and estimates the contribution of genetic, shared and unique environmental influences on substance use.

Method: Substance use data were collected using the Child and Adolescent Psychiatric Assessment on a population sample of 1,412 male and female monozygotic and dizygotic twin pairs, aged 8 through 16, from the Virginia Twin Study of Adolescent Behavioral Development.

Results: Heritabilities were estimated to be 84% and 82% for liability to lifetime and current tobacco use, respectively.

Generation and function of bone marrow-derived dendritic cells from CD4/CD8(-/-) double-knockout mice.

We present a novel, simple and straightforward method to obtain mouse bone marrow-derived dendritic cells (DC) from C57Bl/6 CD4/CD8(-/-) double knock-out mice. This new method, involving culture of bone marrow cells in medium supplemented with Interleukin 4 and Granulocyte-Macrophage Colony-Stimulating Factor, does not involve negative immunodepletion of CD4+ and CD8+ populations, or extensive prior manipulations of the starting population. The resulting, loosely adherent cell population, exhibited the morphological characteristics and typical surface markers of DCs, and were endowed with the functional activities characteristic of bone marrow-derived DCs of wild-type mice.

The influence of genetic factors and life stress on depression among adolescent girls.

Background: The possible causes of greater depression among adolescent girls were investigated by examining variation in the influence of genetic and environmental risk factors among 182 prepubertal female, 237 prepubertal male, 314 pubertal female, and 171 pubertal male twin pairs from the Virginia Twin Study of Adolescent Behavioral Development.

Objectives: To compare the trajectory of depressive symptoms among boys and girls from childhood to adolescence; to analyze the role of genetic, shared, and unique environmental factors in depression among prepubertal and pubertal male and female twins; and to investigate a possible link between liability to depression and one salient index of the child's environment: past-year life events.

Methods: Child-reported depression was assessed using the Child and Adolescent Psychiatric Interview and ratings of past-year life events and pubertal status obtained by maternal questionnaire and interview, respectively.

Models for the longitudinal genetic analysis of same-age twins: application to HDL cholesterol.

Models are presented for the analysis of longitudinal data from same-age twins which permit the exploration of a remarkably diverse array of alternative explanations for continuity and change during development. Data of this type permit the detection of new sources of genetic or environmental covariation during development that are not expressed at earlier ages and, because they include the effects of age-specific genes, the resulting heritability estimates are more reliable than those obtained from relatives who differ in age. The proposed models were applied to measurements of HDL cholesterol obtained on 81 pairs of monozygotic (MZ) twins and 69 dizygotic (DZ) pairs at 11, 12.

Genetic and environmental influences on subtypes of conduct disorder behavior in boys.

Oppositional and conduct disorders are a heterogeneous collection of disruptive behaviors associated with diverse risk factors and varying outcomes. Data from males in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) are used to explore the relative importance of genetic and environmental influences on four previously described disruptive subtypes: property violations, status violations, oppositional behavior, and aggression. Striking differences between results according to mother and child ratings are found, indicating the need to consider carefully the origin of rater differences.

Assortative mating for major psychiatric diagnoses in two population-based samples.

Background: Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables.

Interferon gamma impairs the ability of monocyte-derived dendritic cells to present tumour-specific and allo-specific antigens and reduces their expression of CD1A, CD80 AND CD4.

Dendritic cells (DC), the most potent antigen-presenting cells found to date, can be generated from the adherent fraction of peripheral blood mononuclear cells (PBMC) by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. When interferon gamma (IFN-gamma) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MHC II (MHC-DR), CD11a and CD54 were increased. T cell proliferation analysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-gamma only induced weak responses in both activated and naive allogenic CD4(+) and CD8(+) T cells when compared to the reaction elicited by DC cultured without IFN-gamma.

Univariate and multivariate genetic analysis of subcutaneous fatness and fat distribution in early adolescence.

Univariate and multivariate analyses of the genetic and environmental contributions to variance in adipose tissue and adipose tissue distribution were carried out in early adolescents. Stature, weight, body mass index (BMI), and five subcutaneous skinfolds were measured at half-yearly intervals in 105 MZ and DZ twin pairs from 10 to 14 years. The most parsimonious model, which provided an adequate explanation for variation in the BMI, five skinfolds, and the T/E ratio, included additive genetic and specific environmental factors.

Genetic "clocks" and "soft" events: a twin model for pubertal development and other recalled sequences of developmental milestones, transitions, or ages at onset.

We propose and explore a twin model to examine the basis for synchrony that often characterizes different facets of normal development. In so doing we also present an approach to the analysis of "soft" events; events for which available reports of dates or ages of occurrence are unreliable or inconsistent. Discrepancies among reports are accounted for by a statistical measurement model.

Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced CD3zeta and CD16zeta chain down-regulation in human peripheral blood lymphocytes and lymphokine-activated killer cells.

We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form of Procysteine, kindly donated by Transcend Therapeutics] could protect peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells from CD3zeta and CD16zeta chain down-regulation induced by H2O2 produced by lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance glutathione production in cells in which glutathione was depleted by reactive oxygen species. Our data showed that OTC induced a significant increase in CD3zeta and CD16zeta chain expression in peripheral blood lymphocytes and LAK cells, respectively, pretreated for 12 hr at 37 degrees.

Inheritance of static and dynamic arm strength and some of its determinants.

Maximal static, eccentric and concentric torques and arm components estimated by anthropometry and measured by computed tomography were evaluated in 25 male monozygotic twins and 16 dizygotic twins (22.4 +/- 3.7 years).

Strength training: importance of genetic factors.

Purpose: This study focuses on the quantification of genetic and environmental factors in arm strength after high-resistance strength training.

Methods: Male monozygotic (MZ, N = 25) and dizygotic (DZ, N = 16) twins (22.4 +/- 3.

Genetic effects on ADHD symptomatology in 7- to 13-year-old twins: results from a telephone survey.

The magnitude of genetic and environmental factors and the influence of contrast effects on attention-deficit hyperactivity disorder (ADHD) symptomatology were examined on a sample of 900 twin pairs, aged 7-13, participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). In addition, the genetic and environmental correlations between ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatology were estimated. A series of structural models was applied to maternal ratings from a telephone survey, designed to screen for the three dimensions of ADHD symptomatology (hyperactivity, impulsivity, and inattention) and ODD/CD symptomatology.

Immunological relatedness of the protective mechanisms against tuberculosis and cancer.

Background: Bacille Calmette-Guérin (BCG), an attenuated strain of tuberculous bacillus, is the source of vaccines providing unclear and variable protection against tuberculosis (TB) and cancer. Thermostable macromolecular antigens (TMAs) are major mycobacterial complexes immunodominant in disease. A60 (TMA complex of BCG) protects mice against TB development, via T lymphocyte (TL)-mediated macrophage (Mphi) activation, halting intracellular mycobacterial replication.

Genetics and developmental psychopathology: 2. The main effects of genes and environment on behavioral problems in the Virginia Twin Study of Adolescent Behavioral Development.

Little is known about the contribution of genetic and environmental factors to risk for juvenile psychopathology. The Virginia Twin Study of Adolescent Behavioral Development allows these contributions to be estimated. A population-based, unselected sample of 1412 Caucasian twin pairs aged 8-16 years was ascertained through Virginia schools.

Genetics and developmental psychopathology: 1. Phenotypic assessment in the Virginia Twin Study of Adolescent Behavioral Development.

We introduce an overlapping cohort sequential longitudinal study of behavioral development and psychopathology in a representative sample of 1412 pairs of twins aged 8 through 16 years. Multiple phenotypic assessments involve a full psychiatric interview with each child and each parent, and supplementary parental, teacher, and child interview material and questionnaires. For the first wave of assessments, the numbers of reported DSM-III-R symptoms of Major Depressive Disorder (MDD), Separation Anxiety Disorder (SAD), Overanxious Disorder (OAD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), and Attention Deficit Hyperactivity Disorder (ADHD), assessed through interviews, confirm patterns of age and sex trends found in other epidemiological samples, but underscore their dependence on whether the child or the parent is the informant.

The Virginia Twin Study of Adolescent Behavioral Development. Influences of age, sex, and impairment on rates of disorder.

Background: The Virginia Twin Study of Adolescent Behavioral Development is a cohort-longitudinal epidemiological study that uses the genetic twin design to study the development and maintenance of child psychiatric disorders. We determined the rates of DSM-III-R disorders, disorders with impairment, and age, sex, and comorbidity effects.

Methods: Families of 2762 white twins aged 8 to 16 years participated.

Genetic and environmental factors in relative body weight and human adiposity.

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%.

Conversion of in vitro cultured human monocytes into effective presenters of an HER2/neu-encoded CTL peptide epitope.

Tumour-derived peptides have been surveyed, in a variety of systems, for their ability to elicit cytokine release from class I restricted T cells. Analogous studies on ovarian carcinoma have employed the antigen-processing defective T2 cell line, Purified dendritic cells (DC) have been reported to act as highly effective APC. A facile method was developed whereby DC-like cells were generated from monocyte precursors.

Gender-specific regional changes in genetic structure of muscularity in early adolescence.

Genetic and environmental influences on muscle circumference measurements of the extremities were estimated in 105 pairs of twins between 10 and 14 yr of age. Four circumferences, extended upper arm (EAC), forearm (FC), thigh (TC), and calf (CC), were measured. Univariate model fitting revealed that the largest part (87-95%) of the variance for all circumferences at most ages was explained by additive genetic factors.

Multivariate genetic analysis of maximal isometric muscle force at different elbow angles.

The maximal isometric moment at five different elbow joint angles was measured in 25 monozygotic and 16 dizygotic male adult twin pairs (22.4 +/- 3.7 yr).

Can negative self-schemes in depressives be altered through sleep deprivation?

This paper addresses the question whether negative cognitive style represents a state or trait variable of depressive patients. For this reason, it studies the influence of sleep deprivation on negative self-schemes of those patients. 10 patients suffering from DSM-III-R major depression were compared with 10 age- and sex-matched controls on a task for rating the self-descriptiveness of positive and negative adjectives as well as a subsequent word recognition task.

Inheritance of physical fitness in 10-yr-old twins and their parents.

This study focuses on the quantification of genetic and environmental sources of variation in physical fitness components in 105 10-yr-old twin pairs and their parents. Nine motor tests and six skinfold measures were administered. Motor tests can be divided into those that are performance-related: static strength, explosive strength, running speed, speed of limb movement, and balance; and those that are health-related: trunk strength, functional strength, maximum oxygen uptake, and flexibility.

Genetic and environmental influences on the covariation between hyperactivity and conduct disturbance in juvenile twins.

Structural equation models were applied to the maternal ratings of 265 MZ and 163 DZ male-male, 347 MZ and 160 DZ female-female, and 262 male-female twin pairs, aged 8-16 years, who participated in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Substantial additive genetic influences and contrast effects were found for hyperactivity, and additive genetic and shared environmental effects or positive comparison effects (particularly for the girls) for oppositional/ conduct disturbance. Bivariate model fitting showed that the covariation between hyperactivity and oppositional/conduct problems in both younger and older boys and girls is almost entirely attributable to genetic factors.