Biomedical subjects

H Maes

Publications and source records attributed to H Maes.

At least 19 recordsLinked to original sources

PubMed2000

Auditory and visual event-related potentials in alcoholics: abnormalities of components and brain electrical field.

Alterations of ERPs recorded over midline scalp sites have frequently been reported in alcoholics. To assess the P3 and other ERP components topographically, auditory and visual ERPs were recorded from 33 scalp electrodes in abstinent alcoholics and healthy controls using an oddball paradigm. At the Cz electrode the alcoholics showed decreased visual N1 and increased auditory N2 amplitudes. Topographically, the negative centroids of the visual N1 and P3 and the auditory N2 differed between groups, and the positive centroid of the visual P3 was displaced toward the right hemisphere. While no valid diagnostic classification could be obtained by using the traditional ERP component P3 recorded from Pz, the combination of visual N1 and auditory N2 amplitudes at Cz with centroid parameters amounted to 51% explained variance and 92% correct discrimination of alcoholics from controls. Abnormalities of N1 amplitude and P3 topography similar to the current findings in alcoholics have previously been described for schizophrenics.

Adult↗

PubMed2000

An evaluation of different approaches for behavior genetic analyses with psychiatric symptom scores.

We used a simulation study to evaluate six approaches for behavior genetic analyses of psychiatric symptom scores. For the selection of the correct model, the best results were obtained with approaches using transformed scores in combination with a procedure involving p-values. With normalizing transformations, the chi 2 test statistic gave a reasonable impression of the overall fit of the model but was less accurate when used as a difference test. The asymptotic distribution free estimation methods yielded chi 2s that were much too large. All data analysis techniques yielded substantially biased parameter estimates. The most biased results were obtained with normalizing transformations. The least biased results were obtained with tobit correlations, but because of its large standard errors the most precise estimates were obtained with polychoric correlations and optimal scale scores. An empirical study showed that a recognition of the role of methodological factors was helpful to understand part of the differences between assessment instruments, raters, and data analysis techniques that were found in the real data.

Adolescent↗

PubMed2000

Genetic and environmental causes of covariation in interview assessments of disruptive behavior in child and adolescent twins.

Multirater, face-to-face, interview data relating to conduct disorder (CD), oppositional-defiant disorder (ODD), and inattentive, impulsive, and hyperactive components of attention-deficit hyperactivity disorder (ADHD) in a population-based sample of 1376 pairs of 8- to 16-year-old MZ and DZ twins are analyzed to examine (1) the genetic and environmental causes of correlation among ratings of ODD and CD symptoms and (2) the pattern of genetic and environmental correlation among the three components of ADHD. Parental ratings of ADHD showed marked sibling contrast effects, specific within raters but partly common across components. After these effects were removed, there was a modest genetic correlation between maternal and paternal ratings, but genetic effects were virtually uncorrelated across boys and girls. Genetic correlations among inattention, impulsivity, and hyperactivity were all large but fell well short of unity. There was little evidence that counts of symptoms of CD and ODD were genetically independent but the genetic correlations among ratings of twins, mothers, and fathers were all relatively modest. ODD and CD showed much higher genetic correlations across sexes than did the measures of ADHD. There was no evidence of rater contrast effects or of shared family environment influences in the twin resemblance for ODD and CD.

Adolescent↗

PubMed1999

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. Of the 22 tested new HER2/neu-derived epitopes that could bind HLA-A2 with high (IC50 < 50 nM) or intermediate (50 nM < IC50 < 500 nM) affinity, we report the recognition by CTL of at least four novel epitopes, including HER2(9435), HER2(9665), HER2(9689), and HER2(10952), and confirm that of the known HER2 (9369) epitope. These epitopes were able to elicit CTL that specifically killed peptide-sensitized target cells and, most importantly, a HER2/neu-transfected cell line and the autologous tumor cells. We also confirm that HER2/neu is overexpressed in several melanoma lines, and as a new finding, report that some of these lines are sensitive to CTL induced by the HER2 (9369), HER2(9435), and HER2(9689) epitopes. Finally, CTL clones specific for HER2 (9369), HER2(9435), and HER2(9689) epitopes were isolated from tumor-specific CTL lines, further demonstrating the immunodominance of these epitopes. These findings broaden the potential application of HER2/neu-based immunotherapy.

Carcinoma↗

PubMed1999

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. RESULTS: The impact of life events on depression was particularly evident in the adolescent girls. The results from model fitting indicate increased heritability for depression in this group, and its long-term consistency was mediated primarily by latent genetic factors. Model fitting also showed that at least part of the liability to depression and to life events can be linked to a common set of genes in the adolescent girls, and there is a notable developmental increase in the genetic variance for life events. CONCLUSIONS: The greater heritability for depression in pubertal girls, its genetic mediation over time, and the increase in genetic variance for life events may be one possible explanation for the emergence of increased depression among pubertal girls and its persistence through adolescence.

Adolescent↗

PubMed1999

Comparing the biological and cultural inheritance of personality and social attitudes in the Virginia 30,000 study of twins and their relatives.

Measures of four dimensions of personality (Psychoticism, Extraversion, Neuroticism, and Lie scores) and six aspects of social attitudes (to sex, taxation, militarism, politics, religion and a general conservatism scale) were obtained by mailed questionnaire from 29,691 US subjects including adult twins (n = 14,761) their parents (n = 2360), their spouses (n = 4391), siblings (n = 3184) and adult children (n = 4800). After correction for the average effects of age, sex and source of sample, familial correlations were computed for 80 distinct biological and social relationships. The data allow for the estimation of the additive and non-additive effects of genes, assortative mating, vertical cultural inheritance and other non-parental effects of the shared environment on differences in personality and social attitudes. The interaction of genetic and environmental effects with sex may also be analyzed. Model-fitting analyses show that personality and social attitude measures differ markedly in major features of family resemblance. Additive and dominant genetic effects contribute to differences in both personality and attitudes, but the effects of the family environment, including vertical cultural transmission from parent to child, are much more marked for social attitudes than for personality. There is substantial assortative mating for social attitudes and almost none for personality. The causes of family resemblance depend significantly on sex for almost every variable studied. These findings clarify and extend the more tentative findings derived from previous twin, family and adoption studies.

Adult↗

PubMed1998

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. Furthermore, the DC derived from cultures with IFN-gamma, loaded with an immunogenic peptide derived from the HER2/neu protein [HER2 (9466)], only induced low levels of TNF release and weak proliferative responses in a specific cytotoxic CD8(+) T lymphocyte clone. Therefore, our results indicate that IFN-gamma negatively influences the differentiation and function of monocyte-derived DC by affecting the expression of surface molecules involved in their antigen-presenting function. This supports the general hypothesis that there exists a feedback immune regulatory mechanism between T cells and monocytes/DC.

Antigens, CD↗

PubMed1998

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. This combines current status error reflecting uncertain definition of onset and two mechanisms for the phenomenon of "telescoping," namely, systematic compression of the time scale and heteroscedastic random measurement error. Statistically, the model can be viewed as a mixed generalized linear model with random effects within both mean and variance functions or, alternatively, as involving multiplicative random effects. We apply the model to multiple maternal reports on menarche and onset of breast development in twin daughters. Fitted to data from the Virginia Twin Study Of Adolescent and Behavioral Development by the use of penalized/predictive quasi-likelihood, the model provided much improved estimates of the true age-at-onset distribution as compared to those from a naive analysis. Results suggested that the observed variance was made up almost entirely of genetic variance and measurement error variance due to telescoping and current status errors and that the timing of breast development and menarche are largely under the control of a common set of genes. Results also indicated that maternal recollections of the onset of breast development were both more poorly defined and subject to greater recall errors than maternal recollections of menarche.

Adolescent↗

PubMed1998

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. In most A60-primed mice, cytolytic TLs and Mphi infiltrate cancer tissue, resulting in 80-100% rejection. Adoptive TL transfer is indispensable for Mphi-dependent tumour cell inactivation via oxygen and nitrogen radicals. Neoplasm development induces immune anergy with depletion ofA60-specific TL and activated Mphi. A60 protects mice against TB and cancer by inducing the synthesis of three lymphokines: interleukin 2 (IL-2), interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). Tumour cells prevent A60-dependent synthesis of these lymphokines in vivo and in vitro. CONCLUSION: These data provide some clues to immune surveillance and tumour escape mechanisms, as well as to the antituberculous and antineoplastic BCG action.

Animals↗

PubMed1998

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, 12.5 and 14 years of age. All three MZ co-twin correlations were substantially higher than the self correlations across occasions, suggesting that new sources of genetic or environmental covariation must be expressed during early adolescence. This interpretation was confirmed by analysis of the full covariance matrices which showed that only models which assumed the expression of new or age-specific genes could explain the observed pattern of covariation. Because they include the effects of age-specific genes, the resulting heritabilities (0.80-0.83) were substantially higher than many previous estimates.

Adolescent↗

PubMed1998

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. Child ratings indicate support for a general genetic liability, with greatest influence on property violations, oppositional behavior and aggression. Maternal ratings suggest that the genetic factors influencing conduct disorder behavior are more specific to the behavioral area, with the stronger genetic influence on property violations and aggression.

Adolescent↗

PubMed1997

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. Three sessions were involved: an initial session (baseline), the second following a night of sleep deprivation, and the third after a successive full night's sleep. During the baseline examination, depressives showed a relatively negative cognitive bias; that is, the same number of positive and negative self-scheme elements. In comparison to controls, they showed significantly more negative and significantly less positive self-scheme elements. The same pattern emerged in a word recognition task for the number of recognized self-scheme elements. These variables indicated no change in the depressive group following sleep deprivation. Depressive subjects' reaction times on self-descriptiveness rating were significantly longer for positive than for negative self-scheme elements at the baseline session. The opposite was true for controls. Here, a sleep deprivation effect was evident. There was no longer a difference in the speed of information processing for positive as compared to negative self-scheme elements. This applied to both depressive and control groups.

Adult↗

PubMed1997

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. Correlations across domains for symptoms reported by the same informant are often as large as correlations across informants for the same domain of symptoms. Factor analyses of these symptom counts, taking account of informant view and unreliability of assessment, show the high degree of correlation between SAD and OAD, between MDD and OAD, and between CD and ODD. ADHD symptoms are relatively independent of the other domains, but show moderate correlations with CD, ODD, and MDD. Factorially derived dimensional questionnaire scales, based on child, parental, and teacher reports, show patterns of relationship to symptom counts consistent with both convergent and discriminant validity as indices of liability to clinical symptoms. Across informants, questionnaire scales provide as good a prediction of symptoms as do clinical interviews. Multitrait-multimethod confirmatory factor analysis reveals the patterns of relationship between symptoms of psychiatric disorder in children taking due account of informant and unique sources of variance. Gender differences are consistent within the correlated clusters of ODD/CD and MDD/SAD/OAD, although there are disorder-specific age trends. There are large informant-specific influences on the reporting of symptoms in clinical interviews. Dimensional questionnaire scales provide a useful source of additional information. In subsequent analyses of genetic and environmental etiology of childhood psychopathology we must expect that results may differ by informant and method of assessment. Multivariate and developmental analyses that explore the sources of these differences will shed new light on the relationship between genetic and environmentally influenced vulnerability and the manifestation of psychopathology in specific circumstances.

Adolescent↗

PubMed1996

Heterogeneity among juvenile antisocial behaviours: findings from the Virginia Twin Study of Adolescent Behavioural Development.

The examination of heterogeneity in antisocial behaviour was accomplished by applying latent class analytic methods to multivariate categorical data on 389 same-sex male twins, aged 11 to 16 from the Virginia Twin Study of Adolescent Behavioural Development (VTSABD). The data included multiple measures of oppositional and conduct disorder, attention deficit disorder, hyperactivity, impulsivity, reading disability and anxiety from mother, teacher, and child report from both questionnaire and interview (child and adult psychiatric assessment; CAPA). A latent four-class model provided a good fit to the data and yielded four phenotypically and aetiologically distinct latent classes: (1) a non-symptomatic class influenced by both additive genetic and shared environmental factors; (2) a hyperactivity-conduct disturbance class accounted for by both additive and non-additive genetic effects; (3) a 'pure' conduct disturbance class with a very strong shared environmental component; and (4) a multisymptomatic class explained entirely by the additive effect of the genes. Further characterization of these four latent classes by age of the child and parental psychiatric history is also shown.

Adolescent↗

PubMed1996

In vitro analysis of cancer prevention by a mycobacterial antigen complex and of cancer-promoted inhibition of immune reactions.

The antigen complex A60 of Mycobacterium bovis bacillus Calmette-Guérin protected mice against experimental tuberculous infection, and prevented cancer development after challenge with EMT 6 cells. Although humoral and cellular immune reactions elicited by A60 in vivo remained unaffected in cases of tumor rejection, they were suppressed in the case of neoplastic growth. In the present work, these in vivo observations were analyzed by in vitro techniques. Activated macrophages played a major role, and cytolytic T lymphocytes a minor role, in A60-promoted cancer cell cytolysis leading to tumor rejection. In vitro, EMT 6 cells weakly inhibited the proliferation of A60-specific B lymphocytes and strongly inhibited the functions of activated macrophages. However, the collapse of both humoral and cellular immune reactions during the course of cancer development was also accompanied by an inhibitory action of EMT 6 cells on the multiplication and functions of A60-specific T lymphocytes. Tumor-dependent repression of macrophage activation was therefore due to both a direct action of tumor cells on macrophages and an indirect one via inhibition of macrophage-activating T cell functions. On the other hand, tumor-induced collapse of the anti-A60 Ig synthesis was mainly due to inhibition of B-cell-activating T cells, with a weaker direct effect of tumor cells on B lymphocytes. Consequently, A60 and tumor cells exert opposite effects on the immune system at several levels.

Animals↗

PubMed1996

Comparison between bacillus Calmette-Guérin and the A60 mycobacterial antigen complex used as cancer-preventive immunotherapies.

Preparations of liver or lysates of Mycobacterium bovis strain Calmette-Guérin (BCG) have long been used as treatments for a variety of cancer types, especially those involving the urinary tract, with varying success. This study was conducted to compare the antitumoral activity of BCG and the thermostable macromolecular antigen complex of BCG (A60) when used as preventive treatments, in conjunction with or without tumor antigens, against growth and dissemination of the EMT6 murine tumor cell line. It was demonstrated that tumor antigens alone did not significantly alter the oncological indexes, although a slight increase in both T lymphocyte and macrophage activations was found. It was further demonstrated that A60 induces a protective activity up to 40% greater than that of live BCG and that this protection was not accompanied by any of the adverse effects sometimes observed during BCG immunotherapy.

Animals↗

PubMed1996

Multivariate multipoint linkage analysis of quantitative trait loci.

Resolution of the genetic components of complex disorders may require simultaneous analysis of the contribution of individual quantitative trait loci (QTLs) to multiple variables. A likelihood approach is used to illustrate how the complexities of multivariate data may be resolved with multipoint linkage analysis. Sibling pair data were simulated from a model in which two QTLs and trait-specific polygenic effects explained all the sibling resemblance within and between five variables. Multipoint linkage analysis was used to obtain individual pair probabilities of having zero, one, or two alleles identical by descent, and these probabilities were applied in a weighted maximum-likelihood fit function. The results were compared with those obtained using conventional linear structural equation modeling to estimate the contribution of latent genetic factors to the genetic covariance in the multiple measures. Both analyses were conducted using the Mx package. Relatively poor agreement was found between genetic factors defined in purely statistical terms by varimax rotation of the first two factors of the genetic covariance matrix and the structure obtained by fitting a model jointly to the phenotypic and the multipoint linkage data.

Animals↗

PubMed1996

Synthesis of cytokines during tumour development in mice immunized with the mycobacterial antigen complex A60.

The authors have previously reported on the ability of A60, an immunodominant antigenic complex of Mycobacterium bovis BCG, to prevent cancer development in mice challenged with EMT 6 tumour cells. Such effect proved to rely on neoplastic cell lysis by cytolytic T lymphocytes and activated macrophages. The involvement of cytokines in triggering the immune response leading to tumour rejection is analysed in the present work. The synthesis of IL-2, IFN-gamma and TNF-alpha was strongly increased in A60-primed mice. Cancer development depressed the blood levels of these three cytokines. In vitro cultures of lymphocytes from lymph nodes and blood of A60-primed mice produced higher levels of these cytokines in the presence of A60, as compared to cultures lacking A60. Such effect was inhibited by co-incubation of lymphocytes with EMT 6 tumour cells In vitro cultures of macrophages yielded higher levels of TNF-alpha in the presence of A60 and co-incubation of these cells with EMT 6 tumour cells also inhibited TNF-alpha production. The enhanced synthesis of IL-2 and IFN-gamma, which promote activation of cytolytic T lymphocytes and macrophages, accounts for the increased tumour cell lysis induced in vivo by A60. The A60-promoted synthesis of TNF-alpha is partly responsible for the latter effect. The inhibitory action of EMT-6 tumour cells on cytokine synthesis is a powerful mechanism of tumour escape from the immune system's control.

Animals↗