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PubMed2006

Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls.

BACKGROUND: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. METHODS: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. RESULTS: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. CONCLUSION: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.

Adult↗
PubMed2006

Identifying metabolic enzymes with multiple types of association evidence.

BACKGROUND: Existing large-scale metabolic models of sequenced organisms commonly include enzymatic functions which can not be attributed to any gene in that organism. Existing computational strategies for identifying such missing genes rely primarily on sequence homology to known enzyme-encoding genes. RESULTS: We present a novel method for identifying genes encoding for a specific metabolic function based on a local structure of metabolic network and multiple types of functional association evidence, including clustering of genes on the chromosome, similarity of phylogenetic profiles, gene expression, protein fusion events and others. Using E. coli and S. cerevisiae metabolic networks, we illustrate predictive ability of each individual type of association evidence and show that significantly better predictions can be obtained based on the combination of all data. In this way our method is able to predict 60% of enzyme-encoding genes of E. coli metabolism within the top 10 (out of 3551) candidates for their enzymatic function, and as a top candidate within 43% of the cases. CONCLUSION: We illustrate that a combination of genome context and other functional association evidence is effective in predicting genes encoding metabolic enzymes. Our approach does not rely on direct sequence homology to known enzyme-encoding genes, and can be used in conjunction with traditional homology-based metabolic reconstruction methods. The method can also be used to target orphan metabolic activities.

Energy Metabolism↗
PubMed2003

Familial aggregation of components of the multiple metabolic syndrome in the Framingham Heart and Offspring Cohorts: Genetic Analysis Workshop Problem 1.

BACKGROUND: The multiple metabolic syndrome is defined by a clustering of risk factors for cardiovascular disease. We sought to evaluate the familial correlations of the components of the syndrome using data from the Framingham Heart Study original and offspring cohorts as provided for the Genetic Analysis Workshop 13. Measures of plasma cholesterol (total and HDL), body mass index (BMI), and systolic blood pressure were used from selected calendar years of exams. Familial correlations were calculated using FCOR in S.A.G.E. RESULTS: The sibling correlations were relatively high for all measures and exams, from 0.17 for systolic blood pressure to 0.27 for HDL cholesterol. The parent-child correlations were very similar, except for systolic blood pressure. The avuncular correlations were much smaller and the cousin correlations were even smaller. For HDL cholesterol the avuncular correlation was half the sibling correlation and the cousin correlation was half that again. Spousal correlations ranged from 0.07 for systolic blood pressure to 0.34 for BMI. Correlations were somewhat lower from 1984 to 1987 examinations than from 1971 to 1975 examinations, except for spousal correlations for systolic blood pressure and BMI. CONCLUSION: The results of the family pair correlations are suggestive of genetic determinants of lipid levels and BMI. These components have been shown to be predictive of cardiovascular disease as well as diabetes. Genes in common with each of the components might also influence development of cardiovascular disease and diabetes, both complex diseases.

Adult↗
PubMed2003

Relationship between gene co-expression and probe localization on microarray slides.

BACKGROUND: Microarray technology allows simultaneous measurement of thousands of genes in a single experiment. This is a potentially useful tool for evaluating co-expression of genes and extraction of useful functional and chromosomal structural information about genes. RESULTS: In this work we studied the association between the co-expression of genes, their location on the chromosome and their location on the microarray slides by analyzing a number of eukaryotic expression datasets, derived from the S. cerevisiae, C. elegans, and D. melanogaster. We find that in several different yeast microarray experiments the distribution of the number of gene pairs with correlated expression profiles as a function of chromosomal spacing is peaked at short separations and has two superimposed periodicities. The longer periodicity has a spacing of 22 genes (approximately 42 Kb), and the shorter periodicity is 2 genes (approximately 4 Kb). CONCLUSION: The relative positioning of DNA probes on microarray slides and source plates introduces subtle but significant correlations between pairs of genes. Careful consideration of this spatial artifact is important for analysis of microarray expression data. It is particularly relevant to recent microarray analyses that suggest that co-expressed genes cluster along chromosomes or are spaced by multiples of a fixed number of genes along the chromosome.

Animals↗
PubMed1992

Characterization of the 5'-flanking region of the rat thyrotropin receptor gene.

Genomic clones containing 1.7 kilobases of the 5'-flanking region of the rat TSH receptor (TSHR) plus coding sequence from the ATG initiation codon [1 basepair (bp)] to the start of the first intron (170 bp) have been isolated and characterized. RNAase protection, primer extension, and cDNA sequences cloned by the anchored polymerase chain reaction identified multiple transcriptional start sites, the major ones clustered between -89 to -68 bp. This portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC rich but has no GC box motif, and has features of promoters seen in "housekeeping" genes. Chimeras containing 1.7 kilobases (-1707 to -2 bp) of the 5'-flanking region, or deletions thereof, and the bacterial chloramphenicol acetyltransferase (CAT) gene expressed significant CAT activity when transfected into rat thyroid cell lines, FRTL-5 and FRT, but not BRL rat liver or HeLa cells. TSH decreased CAT activity in the FRTL-5 thyroid cells that had been stably transfected with the TSHR-CAT chimeric constructs. Negative regulation of promoter activity by TSH was duplicated by 10 microM forskolin in FRT thyroid cells, which express no TSHR mRNA. Deletion analyses indicated that a "minimal" region, exhibiting promoter activity, tissue specificity, and negative regulation by TSH, is located between -195 and -39 bp; this region is highly conserved in rat and human TSHR genes. Differential digestion of genomic DNA by MspI and HpaII revealed that the TSHR promoter is methylated in FRT, but not FRTL-5, cells; methylation of the promoter may be associated with loss of endogenous TSHR gene expression in FRT cells.

Amino Acid Sequence↗
PubMed1994

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development.

The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface receptors required to mediate cell-cell and cell-matrix adhesion. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serve such a function. It is a member of the immunoglobulin superfamily expressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosaminoglycans, as well as by a homophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhesion molecules on naive T cells. This report documents by RT-PCR and immunohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently within the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides were missing from the cytoplasmic domain. The sequence and location of the deleted polypeptides corresponded to exons found in the human PECAM-1 gene. The alternatively spliced isoforms were capable of mediating cell-cell adhesion when transfected into L-cells. The isoforms differed, however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodies. This is the first report of naturally occurring alternatively spliced forms of PECAM-1 having possible functional implications.

Amino Acid Sequence↗
PubMed2001

The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis.

The Drosophila imaginal cells that produce epidermal hairs, the shafts of sensory bristles and the lateral extensions of the arista are attractive model systems for studying the morphogenesis of polarized cell extensions. We now report the identification and characterization of furry, an essential Drosophila gene that is involved in maintaining the integrity of these cellular extensions during morphogenesis. Mutations in furry result in the formation of branched arista laterals, branched bristles and a strong multiple hair cell phenotype that consists of clusters of epidermal hairs and branched hairs. By following the morphogenesis of arista laterals in pupae, we have determined that the branched laterals are due to the splitting of individual laterals during elongation. In genetic mosaics furry was found to act cell autonomously in the wing. The phenotypes of double mutant cells argue that furry functions independently of the frizzled planar polarity pathway and that it probably functions in the same pathway as the tricornered gene. We used a P-element insertion allele as a tag to clone the furry gene and found it to be a large and complicated gene that encodes a pair of large conserved proteins of unknown biochemical function.

Amino Acid Sequence↗
PubMed2006

Familial risks for main neurological diseases in siblings based on hospitalizations in Sweden.

Recent successes in identifying the underlying genetic mechanisms for neurological diseases, particularly for their Mendelian forms, have had profound implications for their diagnostics, treatment and classification. However, there has never been an attempt to compare familial risks in a systematic way among and between the main neurological diseases. Familial risks were here defined for siblings who were hospitalized because of a neurological disease in Sweden. A nationwide database for neurological diseases was constructed by linking the Multigeneration Register of 0- to 69-year-old siblings to the Hospital Discharge Register for the years 1987 to 2001. Standardized risk ratios were calculated for affected sibling pairs by comparing them to those whose siblings had no neurological disease. There were three main results. First, it was shown that all disease groups had a familial risk, with the exception of transient ischemic attacks, and the risks could be ranked from the highest (3451) for Huntington's disease to the lowest (2.1) for inflammatory diseases. Second, increased familial risks were shown for disease subtypes for which susceptibility genes or familial clustering have not been demonstrated previously, including multiple sclerosis, sleep apnea, nerve, nerve root and plexus disorders, and cerebral palsy. Third, based on the available sample size there was no convincing evidence for familial comorbidity between the disease groups, suggesting that the factors causing familial aggregation, probably usually heritable genes, are distinct for each subtype. The high familial risks for neurological disease imply heritable etiology and opportunities for identification of further susceptibility genes.

Adolescent↗
PubMed2003

[Determinant factors of functional status among the elderly].

OBJECTIVE: To investigate the impact of health-related demographic and socioeconomic factors, as well as the impact of factors associated to social activity and the subjective health evaluation on the functional status of elderly people. METHODS: A cross-sectional multicentric study was conducted in a representative population sample in the city of São Paulo, Brazil, in 1989. Functional status was evaluated using a scale of activities of personal and instrumental daily living. It was studied as a dichotomous variable: absence of dependency - disability/difficulty in none of the activities in contrast with moderate/severe dependency - disability/difficulty in 4 or more activities. Multiple regression analysis was applied to hierarchically clustered factors. RESULTS: Those with the following features were more associated to moderate/severe dependency: illiterate, retired, pensioner, house keeper, living in a rented home, age over 65 years, multigenerational family composition, hospitalization in the last 6 months, mental health screening case, no visiting friends, and having a pessimistic perception of his/her own health when compared to their peers. CONCLUSIONS: The identified features associated to moderate/severe dependency suggest a complex net of causes for the declining functional status. However, one can assume that preventive measures directed to specific factors can benefit these population by improving their well-being.

Activities of Daily Living↗
PubMed2001

Selected lifestyle and risk behaviors associated with adolescents' smoking.

A selected number of lifestyle and risk behaviors of adolescents in relation to their smoking were studied using both longitudinal and cross-sectional analyses. Data of a national sample of 4,431 nonsmoking adolescents who participated in the 1989 Teenage Attitudes and Practices Survey and were re-interviewed in 1993 were analyzed. Adolescents who engaged in physical fights, engaged in drunk driving, and were risk-takers were more likely to be regular experimental smokers than adolescents who did not exhibit these behaviors. The data suggest that high-risk behaviors may cluster. Interventions may be necessary to target multiple risk behaviors and be more effective in changing adolescents' risk behaviors associated with smoking.

Adolescent↗
PubMed2005

[Anger and health status in late school-age children].

PURPOSE: This cross-sectional study was designed to identify anger-expression types in late school-age children and investigate the relation between the identified anger-expression types and their health status. METHOD: One thousand twenty seven children in elementary school fifth and sixth grades were recruited from November to December, 2004. Data was analyzed using descriptive statistics, cluster analysis, 2-test, ANOVA, Duncan's multiple comparison test, and Wilcoxon rank sum test. RESULTS: Three anger-expression types in late school-age children were found; Anger-out/in, Anger-control, and Low anger-expression types. Children frequently using the anger-out/in type among the three types and with a higher state anger reported higher psychosomatic symptoms and depression. Children from a divorced or separated family reported higher state anger. CONCLUSION: This study suggests that a specific anger management program needs to be developed for late school-age children with high state anger and frequently using the anger out/in expression type. For understanding the anger level and the anger expression types of Korean school-age children, further research needs to be done with large samples using a randomized sampling method.

Anger↗
PubMedDate not supplied

Antecedents of adolescent initiation of sex, contraceptive use, and pregnancy.

OBJECTIVE: To identify the most important antecedents associated with adolescent initiation of sex, contraceptive use, and pregnancy. METHODS: Statistically significant antecedents in more than 250 studies were identified and summarized. RESULTS: More than 100 antecedents create a complex and detailed picture of the correlates of adolescent sexual behaviors. They describe characteristics of the adolescents themselves, their partners, peers, families, schools, and communities, as well as relationships to these entities. They included antecedents that were inherently sexual and nonsexual. CONCLUSIONS: To reduce teen pregnancy substantially, multiple sexual and nonsexual antecedents in different clusters may need to be addressed.

Adolescent↗
PubMed1992

The distribution of DNA sequences hybridizing with antibiotic production and resistance gene probes within type strains and wild isolates of Streptomyces species.

Total DNA preparations from 74 antibiotic-producing type strains and 102 natural Streptomyces isolates were examined by dot blots for homology to 6 antibiotic production and resistance genes. Pattern diversity of hybridizations decreased as stringency increased from 65% to 85%. There were 146 unique profiles at 65% stringency with 13 repeated patterns, whilst there were only 14 unique and 11 repeated profiles at 85% stringency. Most of the strains which hybridized at 85% reacted with one or two probes although a few strains showed multiple homologies. This data was used to cluster strains and the groups defined were examined for phenotypic antibiotic resistance. Producers of certain classes of antibiotics clustered to specific groups and some gene homologies were more common amongst strains which produced similar antibiotics.

Anti-Bacterial Agents↗
PubMed2000

[Diagnostic criteria of insulin resistance and multiple risk factor syndrome].

Multiple risk factor syndrome (MRFS) is a clustering of cardiovascular risk factors, which describes the epidemiological association of glucose intolerance, central obesity, hypertension, increased triglyceride level and decreased HDL-cholesterol, leading to the atherosclerosis. Insulin resistance is diagnosed clinically by fasting hyperinsulinemia, steady state plasma glucose (SSPG) method, insulin tolerance test and glucose clamp study. Visceral fat accumulation is supposed to play a central role in pathogenesis of MRFS and induces risk factors for cardiovascular disease through the increased TNF-alpha expression in adipose tissue and serum FFA level, which cause insulin resistance state. These risk factors should be prevented at early stage by the intervention in obesity, especially visceral fat accumulation.

Adipose Tissue↗
PubMed1975

[Hodgkin's disease: an epidemiological study on 140 children--urban/rural relation, profession of parents, domestic animal contact].

In Northern Germany (Schleswig-Holstein, Niedersachsen, Hamburg and Bremen) 140 children aged 2-14 years who had developed Hodgkin's disease after World War II were identified with the help of all 54 children's hospitals, the 101 local public health offices, and the Hamburg Cancer registry etc. Only histologically confirmed cases were included. For boys, comparison by urban and rural residence showed a preponderance of cases in rural areas (places with less than 2000 inhabitants). This urban-rural difference became statistically significant (P less than 0.05) when the cases reported from Hamburg (with its greater registration intensity) were excluded. For girls, there was no difference in the urban/rural distribution. Personal interviews were conducted with 133 case families. One third of the parents had been engaged in agricultural occupations. In the retrospective studies contacts with domestic animals was most impressive, especially those with rabbits (84.2%). But there was also contact with large animals, most frequently with pigs (45.9%). The difficulties of getting suitable controls--because of the widespread and changing keeping of animals--are discussed. A matched pair analysis of the 21 children from Hamburg confirmed significance (P less than 0.05) for contact with domestic rabbits.-- Furthermore, multiple cases (in family or in neighbourhood, "cluster") could mostly be linked together by contacts with the same herd. The epidemiological results from the basis of a hypothesis that Hodgkin's disease is a zoonosis. The possibility of a synergistic action of two factors--transmitted by two different species--is discussed.

Adolescent↗
PubMed2004

[Health behaviors of middle-aged adults].

Middle age is the term used to describe the transition between early and late adulthood. Declining physical functions and increased stress resulting from family and work obligations create important health challenges among middle-aged adults, therefore maintaining good health behaviors is particularly important for members of this population. Work responsibilities make it particularly hard for many middle-aged adults to participate in health-related activities. The purpose of this paper is to integrate literature related to health behaviors of middle-aged adults to understand their behavior practice and characteristics. In Taiwan, middle-aged adults (especially male breadwinners) are more likely to use tobacco, alcohol, and betel nut, with these behaviors tending to be clustered. Gender-specific strategies for managing multiple substance use and abuse and better enforcement of public health policies are needed to promote positive health behaviors among middle-aged Taiwanese adults.

Female↗
PubMed1991

Structural and functional analysis of the regulatory sequences of the ets-1 gene.

The ets-1 gene is a human homolog of the oncogene v-ets of avian acute leukemia virus E26. The ets-1 gene is preferentially expressed in lymphoid cells. To understand the regulation of the ets-1 gene expression the regulatory sequences of this gene were identified and isolated. The promoter is found to be functioning in the lymphoid cell line Daudi and the erythromyeloid cell line K562 but not in the promyelocytic cell line HL60. Sequence analysis indicates that the ets-1 promoter does not contain the TATA or CAT box. It contains multiple transcription initiation sites in a tight cluster. The promoter contains one binding site each for AP1 and AP2. It has one definitive and five presumptive sp1-binding sites. In addition, the ets-1 promoter contains one ets-1 protein-binding site. Functional analysis has shown that c-jun enhances the activity of the ets-1 promoter, whereas the combination of c-fos and c-jun expressions has no synergistic effect. The expression of exogenous AP2 and ets-1 also enhances the activity of the ets-1 promoter. These results suggest that the AP1, AP2 and ets-1 proteins have a positive regulatory effect. The presence of the ets-1 protein-binding site indicates the existence of an autoregulatory mechanism for the expression of the ets-1 gene. Our results suggested that the presence of a negative regulatory element upstream of the region where most of the positive regulators are located.

Base Sequence↗
PubMed1997

Metaplastic meningioma with lipomatous changes.

We report here relatively rare lipomatous metaplastic changes, probably related to a prolonged clinical course, in not otherwise specified transitional meningioma. This lesion appears to have evolved over 30 years, with the initial diagnosis of multiple sclerosis. Histologically, it was composed of clusters and whorls of polygonal and spindle cells characteristic for transitional meningioma, with large areas of cells with lipid cytoplasmic accumulation, closely resembling mature adipocytes. The lipidization of other brain tumors and the histogenesis of these lesions in meningiomas on the background of meningeal embryogenesis are also discussed.

Adipocytes↗