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Health behaviour, risk awareness and emotional well-being in students from Eastern Europe and Western Europe.

Life expectancy and other indices of health have deteriorated markedly in the former socialist countries of Eastern Europe over recent decades. The possible roles of lifestyles, knowledge about health and behaviour, emotional wellbeing and perceptions of control were assessed in a cross-sectional survey of young adults of similar educational status in Eastern and Western Europe. As part of the European Health and Behaviour Survey, data were collected in 1989-1991 from 4170 university students aged 18-30 years from Austria, Belgium, the Federal Republic of Germany, the Netherlands and Switzerland, and from 2293 students from the German Democratic Republic, Hungary and Poland. Measures were obtained of health behaviours, awareness of the role of lifestyle factors in health, depression, social support, health locus of control, and the value placed on health. After adjustment for age and sex, East European students had less healthy lifestyles than Western Europeans according to a composite index of 11 health behaviours, with significant differences for seven activities: regular exercise, drinking alcohol, avoiding dietary fat, eating fibre, adding salt to food, wearing a seat-belt, and using sunscreen protection. East European students were less likely to be aware of the relationship between lifestyle factors (smoking, exercise, fat and salt consumption) and cardiovascular disease risk. In addition, they were more depressed (adjusted odds of elevated scores on the Beck Depression Inventory of 2.46, 95% C.I. 1.95-3.09), reported lower social support, and had higher beliefs in the "chance" and "powerful others" locus of control. Internal locus of control levels did not differ across regions, and Eastern Europeans placed a higher valuation on their health. Unhealthy lifestyles associated with lack of information about health and behaviour, greater beliefs in uncontrollable influences, and diminished emotional well-being, may contribute to poor health status in Eastern Europe.

Adolescent↗

Mitochondrial and nuclear genes present conflicting portraits of human origins.

Human mitochondrial DNA (mtDNA) sequences reveal an abundance of polymorphic sites in which the frequencies of the segregating bases are very different. A typical polymorphism involves one base at low frequency and the other base at high frequency. In contrast, nuclear gene data sets tend to show an excess of polymorphisms in which both segregating bases are at intermediate frequencies. A new statistical test of this difference finds significant differences between mtDNA and nuclear gene data sets reported in the literature. However, differences in the polymorphism patterns could be caused by different sample origins for the different data sets. To examine the mtDNA-nuclear difference more closely, DNA sequences were generated from a portion of the X-linked pyruvate dehydrogenase E1 alpha subunit (PDHA1) locus and from a portion of mitochondrial control region I (CRI) from each of eight individuals, four from sub-Saharan Africa. The two genes revealed a significant difference in the site frequency distribution of polymorphic sites. PDHA1 revealed an excess of intermediate-frequency polymorphisms, while CRI showed an excess of sites with the low-high frequency pattern. The discrepancy suggests that mitochondrial variation has been shaped by natural selection, and may not be ideal for some questions on human origins.

Cell Nucleus↗

Defective responsiveness of adenylate cyclase to forskolin in the Drosophila memory mutant rutabaga.

The Drosophila memory mutant rutabaga (rut) has been previously shown to have a defective subpopulation (or functional state) of the enzyme adenylate cyclase. We report here that the reduced adenylate cyclase activity is also associated with a defective responsiveness of the enzyme to forskolin. Forskolin activation isotherms of the enzyme in normal membranes reveal low- and high-affinity forskolin-interacting components; the residual enzyme in the mutant shows a smaller proportion of the high-affinity response. In addition, in mutant membrane preparations, forskolin fails to shift the Km of the enzyme for free Mg2+ and for MgATP, in contrast to the situation in the normal tissue. The defect in the responsiveness to forskolin in rut is even more pronounced in a Lubrol-solubilized enzyme preparation, and is due to intrinsic properties of the cyclase system rather than to the absence (or presence) of a soluble, or detergent solubilized, factor in rut. The reduced forskolin responsiveness maps to the X chromosomal segment 12F5-6 to 13A1-5, within the region previously reported to span the locus that controls both the abortive memory and the lack of Ca2+-stimulation of adenylate cyclase in rut17. The possible relevance of the findings to postulated molecular mechanisms of short-term memory formation is discussed.

Adenylyl Cyclases↗

Characterization of T lymphocyte subsets with monoclonal antibodies: discovery of a distinct marker, Ly-m22, of T suppressor cells.

The study of cell surface antigens has accelerated in the few years since the advent of hybridoma technology to the point where many dozens of such markers have now been described. The functional heterogeneity of post-thymic T cells in the immune response, however, still exhibit complexities beyond the resolving power of our current repertoire of marker antigens. In this study, we investigated the surface phenotype of three types of effector T cells: helper cells, nonspecific suppressor cells, and cytotoxic T cells, using four recently discovered alloantigen systems of T cells: Ly-m10, Ly-m18, Ly-m19, and Ly-m22. SRBC-primed spleen cells were used as a source of specific helper T cells, and they were tested by their ability to promote antibody synthesis by B lymphocytes. Concanavalin A-activated suppressor cells were assayed by their ability to inhibit that response. Cytotoxic T cells were activated by alloantigen. We found Ly-m10 to be expressed on all three cell types tested, whereas Ly-m18 and Ly-m19 were absent from all three. Ly-m22, whose controlling locus is closely linked to the Mls region, had a unique distribution, being present solely on suppressor cells. Thus Ly-m22 emerged as a new marker that distinguishes nonspecific T suppressor cells (Ly-m22+) from T helper as well as cytotoxic T cells (Ly-m22-). Ly-m22 is the only antigen besides I-J so far known to be restricted to suppressor cells.

Animals↗

Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-gamma gene.

Th1 and Th2 CD4+ T cell clones have been defined by their ability to produce different lymphokines. However, the processes by which CD4+ T cells differentially regulate lymphokine gene expression have not been well defined. In this report, we demonstrate that the methylation status of a CpG dinucleotide contained within a TATA proximal regulatory element of the IFN-gamma promoter correlates with the transcription of the gene. In murine Th1 clones and two human CD4+ Th0 clones, this site is either completely or partially hypomethylated, whereas in murine Th2 clones this site is > 98% methylated. Treatment of murine Th2 clones with 5-azacytidine, an agent that inhibits methylation of the DNA, converts these cells to IFN-gamma producers. Additional targets for methylation outside the transcriptional control regions of the IFN-gamma genetic locus were found to be hypomethylated in Th2 cells but not in Th1 cells. Electrophoretic mobility shift assays (EMSA) revealed at least five distinct protein-DNA complexes that are formed with an oligonucleotide containing the IFN-gamma promoter TATA proximal regulatory element, and in vitro methylation of this site results in a loss of these three complexes. Furthermore, a comparison of nuclear extracts prepared from Th1 and Th2 clones revealed that the EMSA patterns were qualitatively similar but differed quantitatively. In addition, transient transfection of a murine IFN-gamma promoter-chloramphenicol acetyl transferase (CAT) gene construct into both Th1 and Th2 clones produced CAT activity that was not inducible by anti-CD3, indicating that hypomethylation per se of the promoter alone is not sufficient for inducible gene expression.

Animals↗

New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice.

Experimental allergic encephalomyelitis (EAE), the principal animal model of multiple sclerosis, is a genetically determined phenotype. In this study, analyses of the cumulative disease frequencies in parental, F1 hybrid, and F2 mice, derived from the EAE-susceptible SJL/J strain and the EAE-resistant B10.S/DvTe strain, confirmed that susceptibility to EAE is not inherited as a simple Mendelian trait. Whole genome scanning, using 150 informative microsatellite markers and a panel of 291 affected and 390 unaffected F2 progeny, revealed significant linkage of EAE susceptibility to marker loci on chromosomes 7 (eae4) and 17, distal to H2 (eae5). Quantitative trait loci for EAE severity, duration, and onset were identified on chromosomes 11 (eae6, and eae7), 2 (eae8), 9 (eae9), and 3 (eae10). While each locus reported in this study is important in susceptibility or disease course, interactions between marker loci were not statistically significant in models of genetic control. One locus, eae7, colocalizes to the same region of chromosome II as Orch3 and Idd4, susceptibility loci in autoimmune orchitis and insulin-dependent diabetes mellitus, respectively. Importantly, eae5 and eae7 are syntenic with human chromosomes 6p21 and 17q22, respectively, two regions of potential significance recently identified in human multiple sclerosis genome scans.

Animals↗

Adjacent genetic markers on chromosome 11p15.5 at or near the tyrosine hydroxylase locus that show population linkage disequilibrium with each other do not show allelic association with bipolar affective disorder.

BACKGROUND: Linkage and association studies have suggested genetic susceptibility to bipolar affective disorder in a region of chromosome 11 around the tyrosine hydroxylase locus. We attempted to test the hypothesis that there was allelic association between polymorphisms around the tyrosine hydroxylase locus and bipolar affective disorder. METHODS: A case-control association study was employed using four polymorphic markers, which span a region of approximately 2 cM across the tyrosine hydroxylase locus. RESULTS: No evidence for allelic association between bipolar affective disorder and any of these markers was found. However, linkage disequilibrium between the markers was detected. CONCLUSIONS: This finding diminishes the probability that genes in this region influence susceptibility to bipolar affective disorder, at least in our sample.

Alleles↗

Two-gene control of the expression of a murine Ia antigen.

Two dimensional polyacrylamide gel electrophoresis of Non-Idet P-40 extracts and of specific Ia immunoprecipitates from [35S]methionine-labeled mouse spleen lymphocytes has revealed that the cell surface expression of some Ia antigens appears to be controlled by two genes. One locus, which maps in the I-A subregion, is probably the structural gene for an Ia polypeptide chain. The second locus, which maps between the I-J and H-2D regions, controls whether this I-A encoded molecule (Ae) remains in the cytoplasm or is modified and expressed on the cell surface. Complementation between these two loci allowing surface expression of Ae can occur in the cis or trans chromosomal position. Both the I-A molecule and a polypeptide chain coded for by a locus in I-E are coprecipitated by anti-I-E antibodies, suggesting that these two chains are associated with each other as a multisubunit complex in the cell. Because the ability to complement I-A for Ae expression is a property only of those strains which synthesize an I-E-encoded protein, it is likely that the I-E product itself is regulating the expression of Ae. These observations suggest several mechanisms by which interaction between two I region loci can generate new cell surface molecules. As a result, they may have important implications for understanding the molecular basis of two gene control of immune responsiveness and immune suppression.

Animals↗

[An electrographic analysis of the dynamic change in the functional state of the rat brain after destruction of the locus coeruleus].

Bilateral destruction of the Locus coeruleus in rats was carried out by means of 6-hydroxydopamine injections. Sham-operated animals served as control ones. Electrical activity was recorded in the region of the Locus coeruleus, the dorsal hippocampus, and in the caudatus-putamen complex. Beginning from the second week after surgery in experimental rats was observed a generalization of the theta-rhythm (7-9 Hz) in electrical activity of the Locus coeruleus, hippocampus and the caudatus-putamen complex during orienting-exploratory activity. At the same time such a rhythm was enhanced in animals with motor and orienting-exploratory agitation. In comparison to the sham-operated animals there were no changes in expression in the electrical activity of the subcortical structures of the rhythm of 5-6 Hz, accompanying immobilization state as well as that of 9-11 Hz, accompanying teeth chattering. The dynamics of changes of subcortical electrical activity of rats after the Locus coeruleus destruction may serve an index of the functional state of the animals under the conditions of noradrenergic deficiency. Changes of the brain electrical activity and behaviour of the animals revealed are considered to be a consequence of a relative enhancement of the central serotoninergic regulation of the subcortical structures being caused by a weakening of noradrenergic influences.

Animals↗

Regulation of the expression of the apolipoprotein(a) gene: evidence for a regulatory role of the 5' distal apolipoprotein(a) transcription control region enhancer in yeast artificial chromosome transgenic mice.

OBJECTIVE: The apolipoprotein(a) [apo(a)] gene locus is the major determinant of the circulating concentration of the atherothrombogenic lipoprotein Lp(a). In vitro analysis of the intergenic region between the apo(a) and plasminogen genes revealed the presence of a putative apo(a) transcription control region (ACR) approximately 20 kb upstream of the apo(a) gene that significantly increases the minimal promoter activity of the human apo(a) gene. METHODS AND RESULTS: To examine the function of the ACR in its natural genomic context, we used the Cre-loxP recombination system to generate 2 nearly identical apo(a)-yeast artificial chromosome transgenic mouse lines that possess a single integration site for the human apo(a) transgene in the mouse genome but differ by the presence or absence of the ACR enhancer. Analysis of the 2 groups of animals revealed that the deletion of the ACR was associated with 30% reduction in plasma and mRNA apo(a) levels. Apo(a)-yeast artificial chromosome transgenic mice with and without the ACR sequence were similar in all other aspects of apo(a) regulation, including liver-specific apo(a) expression and alteration in expression levels in response to sexual maturation and a high-fat diet. CONCLUSIONS: This study provides the first experimental in vivo evidence for a functional role of the ACR enhancer in determining levels of apo(a) expression.

5' Untranslated Regions↗

Dealing with extreme environmental degradation: stress and marginalization of Sahel dwellers.

BACKGROUND: Psychological aspects of environmental degradation are hardly investigated. In the present study these aspects were examined among Sahel dwellers, who live in environments with different states of degradation. The degradation was assessed in terms of vegetation cover, erosion, and loss of organic matter. METHOD: Subjects came from three cultural groups: Dogon (agriculturalists, n = 225), Mossi (agriculturalists, n = 914), and Fulani (pastoralists, n = 844). Questionnaires addressing marginalization, locus of control, and coping were administered. RESULTS: Environmental degradation was associated with higher levels of stress, marginalization, passive coping (avoidance), a more external locus of control, and lower levels of active coping (problem solving and support seeking). Compared to agriculturalists, pastoralists showed a stronger variation in all psychological variables across all regions, from the least to the most environmentally degraded. Women showed higher scores of stress, (external) locus of control, problem solving, and support seeking than men. The interaction of gender and region was significant for several variables. CONCLUSION: It was concluded that environmental degradation has various psychological correlates: people are likely to display an active approach to environmental degradation as long as the level of degradation is not beyond their control.

Adaptation, Psychological↗

Influence of MHC on the oncogenicity and immunogenicity of polyoma virus BK in rats.

The oncogenicity of the human papovavirus, type BK, was examined in the Lewis strain of inbred rats, possessing the recombinant alleles "a" and "u" on the MHC TR1 locus. It was found that only haplotypes containing "a" within the B/D locus but not within the A and the C locus of the RT1 region were associated with resistance to the oncogenic potential of BKV and with the capacity of animals to form BKV T antigen antibody. By contrast, the presence of "u" or "l" within the MHC B/D region was linked to the reverse phenotype characterized by sensitivity to the oncogenic effect of BKV and failure to yield T antibody response up to 6 months after inoculation with BK. These results present further evidence of the function as an immune control gene of the B/D region of the RT1 locus of rat MHC.

Animals↗

Effect of repeated seizure experiences on tyrosine hydroxylase immunoreactivities in the brain of genetically epilepsy-prone rats.

The genetically epilepsy-prone rat (GEPR) is a model of generalized tonic/clonic epilepsy, and has functional noradrenergic deficiencies that act as partial determinants for the seizure predisposition and expression. The present study investigated the effect of repeated seizure experiences by acoustic stimulation (110 dB, 10 times) on the immunoreactivities of tyrosine hydroxylase (TH), a rate-determining enzyme in the synthesis of norepinephrine, in brain regions of GEPRs. TH immunoreactivity in locus coeruleus, the major noradrenergic nucleus in brain, was lower in GEPRs than control Sprague-Dawley rats. It was also decreased in several regions including inferior colliculus of GEPRs. Repeated experiences of audiogenic seizures further decreased TH immunoreactivities in locus coeruleus and inferior colliculus of GEPRs. The results from the present study suggest that the lower immunoreactivities of TH in locus coeruleus and inferior colliculus contribute, at least in part, to the noradrenergic deficits in GEPRs, and repeated seizure experiences further intensified these noradrenergic deficits, which may be related to the altered seizure expression by repetitive audiogenic seizure in GEPRs.

Animals↗

Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation.

The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine-labeled human cells. Results of the serological typing of a panel of 25 rodent-human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation.

ABO Blood-Group System↗

Genetic control of the expression of allelic Ig genes at the VH a locus in a1/a2 heterozygous rabbits.

Heterozygous rabbits representing 9 of 15 possible a1 and a2 heavy chain haplotype gene combinations among rabbits in the University of Illinois colony were analyzed for ratios of a1 to a2 in serum immunoglobulin (Ig). The Ig from rabbits of the a1x-y-n81f73g74de12,15 heavy chain haplotype in combination with any of three a2-associated heavy chain haplotypes have higher ratios of a1 to a2 than Ig from rabbits in which a1 is encoded by 4 other heavy haplotypes. For example, the mean a1:a2 ratio for adult a1x-y-n81f73g74de12,15/a2x32y33,- n82,f71g75de12,15 rabbits was 12:1 compared to 5:1 for a1x-y33,30n83,f71g75de12,15/a2x32y33,- n82,f71g75de12,15 heterozygous rabbits. Family studies indicated that the a1:a2 ratio was under the control of the heavy chain chromosomal region or a locus closely linked to it. Whether the regulation is due to varying numbers of VH genes and/or J gene segments, a separate regulator gene, or more efficient joining of certain gene segments, has yet to be determined.

Alleles↗

Fine mapping of a region of rat chromosome 12 close to the aspermia (as) locus and comparison with the human orthologous regions.

The aspermia mutation of the rat exhibits male sterility caused by arrest of spermatogenesis, which is controlled by an autosomal single recessive gene (as). The as locus has been mapped on rat chromosome 12. We recently identified a causative mutation for the aspermia phenotype of the as homozygous rats in the gene encoding Fkbp6, a member of the immunophilins FK506 binding proteins. In this paper, we report the fine mapping of the as locus by linkage analysis combined with comparative mapping using rat, mouse, and human genomic sequences and expression analysis of genes located in the as region. We constructed a fine linkage map of the region of rat chromosome 12 close to the as locus by using 13 microsatellite markers and localized the as locus to a 1.0-cM interval. Comparison of the linkage map with physical maps of rat, mouse, and human refined the as critical region in a 2.2-Mb segment of the rat physical map between the D12Nas3 and D12Nas8 genes, which includes the Fkbp6 gene. A centromeric part of this segment corresponds to the region commonly deleted in Williams syndrome, a human complex developmental disorder, on human chromosome 7q11.23. The expression analysis of 23 genes located on the 2.2-Mb segments in various mouse tissues identified genes exclusively or strongly expressed in the testis.

Animals↗

A functional polymorphism in the promoter region of the tryptophan hydroxylase gene is associated with alcohol dependence in one aboriginal group in Taiwan.

BACKGROUND: Polymorphisms within intron 7 of the tryptophan hydroxylase (TPH1) gene were found to be associated with alcohol dependence in different ethnic groups, including the aboriginal Bunun group in Taiwan. This study aimed to identify genetic variants at the TPH1 locus and to examine their associations with alcoholism. We hypothesized that the polymorphism of TPH1 gene is functional and influences the human circadian rhythm to contribute to the pathophysiology of alcohol dependence. METHODS: DNA from the Taiwanese Han and Bunun was subjected to sequence for screening genetic variation in the coding and promoter regions of the TPH1 locus. Polymorphisms among individuals with alcohol dependence and control subjects in two ethnic groups in Taiwan were investigated. RESULTS: Three variants in the TPH1 promoter region were identified, and the markers are in complete linkage disequilibrium in both populations. Positive associations at both allelic and genotypic levels were obtained between case and control groups in the Bunun. Expression studies demonstrated that the variants indeed affected reporter gene activity in human choriocarcinoma and colon adenocarcinoma cell lines. CONCLUSIONS: Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan. The associations between TPH1 genotypes and alcoholism may deserve further investigation.

Adult↗

The nature of hemopoietic histocompatibility determinants. Differential sensitivity of Hh-1b and H-2b determinants to tunicamycin.

NK cell-dependent resistance of F1 hybrid mice to parental H-2b hemopoietic allografts is directed to cell surface structures controlled by the Hh-1 locus in or near the H-2D region. Crucial to an understanding of this enigmatic phenomenon is the information on the biochemical nature of the Hh-1 locus-controlled structures. Therefore, we examined the effect of tunicamycin (TM), an inhibitor of asparagine-linked glycosylation and ganglioside biosynthesis, on the expression of Hh-1 determinants in H-2b/Hh-1b lymphomas. The Hh-1b determinants on EL-4 and RBL-5 cells were no longer detectable after TM treatment, as demonstrated by the failure of the treated cells to inhibit hybrid resistance to parental H-2b bone marrow cells in vivo. This interpretation was supported by the unaltered ability of the TM-treated cells to localize in the spleens of irradiated F1 hybrid recipients. In contrast, TM caused only moderate reduction in H-2Kb and H-2Db expression as measured by binding of specific antibodies. This was accompanied by reduced susceptibility to alloimmune anti-H-2Db CTL, but not to anti-H-2Kb CTL. No decrease was found in the susceptibility to NK cell cytotoxicity in vitro. These data indicate that N-linked glycosylation or ganglioside synthesis is crucial for the expression of the Hh-1 locus-controlled target structures, but not for the H-2 class I molecules. The data also show that the Hh-1b determinants are substantially different from those which confer the susceptibility to NK cell-mediated in vitro cytotoxicity.

Animals↗