bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of nebulized ketamine on allergen-induced airway hyperresponsiveness and inflammation in actively sensitized Brown-Norway rats
Authors: Zhu Min Min , Zhou Qin Hai , Zhu Mei Hua , Bo Rong Hai , Xu Yu Ming , Qian Yan Ning , Fu Cheng Zhang 
Published: May 2007

Abstract
Since airway hyperresponsiveness (AHR) and allergic inflammatory changes are regarded as the primary manifestations of asthma, the main goals of asthma treatment are to decrease inflammation and maximize bronchodilation. These goals can be achieved with aerosol therapy. Intravenous administration of the anesthetic, ketamine, has been shown to trigger bronchial smooth muscle relaxation. Furthermore, increasing evidence suggests that the anti-inflammatory properties of ketamine may protect against lung injury. However, ketamine inhalation might yield the same or better results at higher airway and lower ketamine plasma concentrations for the treatment of asthma. Here, we studied the effect of ketamine inhalation on bronchial hyperresponsiveness and airway inflammation in a Brown-Norway rat model of ovalbumin(OVA)-induced allergic asthma. Animals were actively sensitized by subcutaneous injection of OVA and challenged by repeated intermittent (thrice weekly) exposure to aerosolized OVA for two weeks. Before challenge, the sensitizened rats received inhalation of aerosol of phosphate-buffered saline (PBS) or aerosol of ketamine or injection of ketamine respectivity. Airway reactivity to acetylcholine (Ach) was measured in vivo, and various inflammatory markers, including Th2 cytokines in bronchoalveolar lavage fluid (BALF), as well as induciable nitric oxide synthase (iNOS) and nitric oxide (NO) in lungs were examined. Our results revealed that delivery of aerosolized ketamine using an ultrasonic nebulizer markedly suppressed allergen-mediated airway hyperreactivity, airway inflammation and airway inflammatory cell infiltration into the BALF, and significantly decreased the levels of interleukin-4 (IL-4) in the BALF and expression of iNOS and the concentration of NO in the inflamed airways from OVA-treated rats. These findings collectively indicate that nebulized ketamine attenuated many of the central components of inflammatory changes and AHR in OVA-provoked experimental asthma, potentially providing a new therapeutic approach against asthma.
Concentrations of TIMP1 mRNA Splice Variants and TIMP-1 Protein Are Differentially Associated with Prognosis in Primary Breast Cancer
Authors: Sieuwerts Anieta M , Usher Pernille A , Meijer-van Gelder Marion E , Timmermans Mieke , Martens John WM , Brünner Nils , Klijn Jan GM , Offenberg Hanne , Foekens John A 
Published: May 2007

AbstractBackground: TIMP-1 protein is a prognostic factor for recurrence-free and overall survival (OS) time in breast cancer. We evaluated the prognostic value of TIMP1 mRNA and a novel TIMP1 mRNA splice variant in 1301 primary breast cancer patients.Methods: We measured mRNA transcripts of full-length TIMP1 (TIMP1-v1) and the novel splice variant lacking exon 2 (TIMP1-v2) by use of real-time RT-PCR in frozen primary tumor samples. Transcript concentrations are correlated with histomorphological and biological factors, TIMP-1 protein, and distant metastasis-free survival (MFS) and OS time.Results: TIMP1-v1 and TIMP1-v2 alone were not informative with respect to predicting prognosis. However, the PCR assay designed to measure the combination of v1 + v2 showed that high concentrations of this combination were associated with good prognosis. In Cox multivariate regression analysis, which also included the traditional prognostic factors, increasing concentrations were independently associated with prolonged MFS (P = 0.004) and OS (P = 0.048). Including TIMP-1 protein and TIMP1-v1+v2 mRNA together in the multivariate model revealed that protein and mRNA were both independently associated with prognosis, with hazard ratios pointing in opposite directions.Conclusion: High concentrations of TIMP1-v1+2 mRNA are associated with good prognosis in patients with primary breast cancer. Since high concentrations of TIMP-1 protein are associated with poor prognosis, the presence of possible posttranscriptional mechanisms requires further investigation.
Parent–Child Feedback Predicts Sibling Contrast: Using Twin Studies to Test Theories of Parent–Offspring Interaction in Infant Behavior
Authors: Eaves Lindon J. , Silberg Judy L. 
Published: May 2007

AbstractSeveral studies report apparent sibling contrast effects in analyses of twin resemblance. In the presence of genetic differences, contrast effects reduce the dizygotic (DZ) twin correlation relative to that in monozygotic (MZ) twins and produce higher DZ than MZ variance. Explanations of contrast effects are typically cast in terms of direct social interaction between twins or an artifact of the process of rating children by their parents. We outline a model for sibling imitation and contrast effects that depends on social interaction between parents and children. In addition to predicting the observed pattern of twin variances and covariances, the parental mediation of child imitation and contrast effects leads to differences in the variance of parents of MZ and DZ twins and differences between the correlations of parents with their MZ and DZ children.
AUTOGSCAN: Powerful Tools for Automated Genome-Wide Linkage and Linkage Disequilibrium Analysis
Authors: Hiekkalinna Tero , Terwilliger Joseph D. , Sammalisto Sampo , Peltonen Leena , Perola Markus 
Published: May 2007

AbstractGenome-wide linkage analysis using multiple traits and statistical software packages is a tedious process which requires a significant amount of manual file manipulation. Different linkage analysis programs require different input file formats, making the task of analyzing data with multiple methods even more time-consuming. We have developed a software tool, AUTOGSCAN, that automates file formatting, the running of statistical analyses, and the summarizing of resulting statistics for whole genome scans with a push of a button, using several independent, and often idiosyncratic, statistical software packages such as MERLIN, SOLAR and GENEHUNTER. We also describe a program, ANALYZE, designed to run qualitative linkage analysis with several different statistical strategies and programs to efficiently screen for linkage and linkage disequilibrium for a given discrete trait. The ANALYZE program can also be used by AUTOGSCAN in a genome-wide sense.
Genetic and Environmental Influences on the Frequency of Orgasm in Women
Authors: Dawood Khytam , Kirk Katherine M. , Bailey J. Michael , Andrews Paul W. , Martin Nicholas G. 
Published: May 2007

AbstractThis study reports on genetic and environmental influences on the frequency of orgasm in women during sexual intercourse, during other sexual contact with a partner, and during masturbation. Participants were drawn from the Australian Twin Registry, and recruited from a large, partly longitudinal twin-family study. Three thousand and eighty women responded to the anonymous self-report questionnaire, including 667 complete monozygotic (MZ) pairs and 377 complete dizygotic (DZ) same-sex pairs, 366 women from complete DZ opposite-sex pairs, and 626 women whose co-twins did not participate. Significant twin correlations were found for both MZ and DZ twin pairs for all three items of interest. Age effects were statistically significant for some items. Models incorporating additive genetic, shared and nonshared environmental influences provided the best fit for Items 1 and 3, while a model with additive and nonadditive genetic influences along with nonshared envir-onment fitted the data from Item 2. While an independent pathway model fits the data most par-simoniously, a common pathway model incorporating additive genetic (A), shared environment (C), and unique environment (E) effects cannot be ruled out. Overall, genetic influences account for approximately 31% of the variance of frequency of orgasm during sexual intercourse, 37% of the variance of frequency of orgasm during sexual contact other than during intercourse, and 51% of the variance of frequency of orgasm during masturbation. Following Baker (1996), we speculate that this additive genetic variance might arise from frequency-dependent selection for a variety of female sexual strategies.
Genetic Markers Data in Survival Studies of Twins: The Results of a Simulation Study
Authors: Begun Alexander Z. , Yashin Anatoli I. 
Published: May 2007

AbstractPrevious longevity studies of related individuals such as twins or siblings based on the major gene model have shown that the frequency and the relative risk of mortality of a beneficial allele in the population could be estimated. If, in addition to survival data for related individuals, the genetic markers data are available, one could try to locate the longevity allele in the genome. In the case where the phenotypic trait is life span or age at onset of disease, a two-step procedure can be used. First, the parameters of bivariate survival functions must be estimated from bivariate survival data for twins without markers. The second step is focused on determining the position of longevity genes between respective markers. To calculate the joint distribution of inheritance vector and genetic markers, the hidden Markov chain technique is used. This approach is illustrated with a simulation example for one longevity gene.
Epistatic and Environmental Control of Genome-Wide Gene Expression
Authors: York Timothy P. , Miles Michael F. , Kendler Kenneth S. , Jackson-Cook Colleen , Bowman Melissa L. , Eaves Lindon J. 
Published: May 2007

AbstractAll etiological studies of complex human traits focus on analyzing the causes of variation. Given this complexity, there is a premium on studying those processes that mediate between gene products and cellular or organismal phenotypes. Studies of levels of gene expression could offer insight into these processes and are likely to be especially useful to the extent that the major sources of their variation are known in normal tissues. The classical study of monozygotic (MZ) and dizygotic (DZ) twins was employed to partition the genetic and environmental influences in gene expression for over 6500 human genes measured using microarrays from lymphoblastoid cell lines. Our results indicate that mean expression levels are correlated about .3 in monozygotic (MZ) and .0 in dizygotic (DZ) twins suggesting an overall epistatic regulation of gene expression. Furthermore, the functions of several of the genes whose expression was most affected by environmental effects, after correction for measurement error, were consistent with their known role in mediating sensitivity to environmental influences.
The Heritability of CHD Mortality in Danish Twins After Controlling for Smoking and BMI
Authors: Wienke Andreas , Herskind Anne M. , Christensen Kaare , Skytthe Axel , Yashin Anatoli I. 
Published: May 2007

AbstractCause-specific mortality data on Danish monozygotic and dizygotic twins are used to analyze heritability estimates of susceptibility to coronary heart disease (CHD) after controlling for smoking and Body Mass Index (BMI). The sample includes 1209 like-sexed twin pairs born between 1890 and 1920, where both individuals were still alive in 1966. The participants completed a questionnaire in 1966 which included questions on smoking, height and weight. The analysis was conducted with both sexes pooled due to the relatively small number of twin pairs. Follow-up was conducted from January 1, 1966 to December 31, 1993. The correlated gammafrailty model with observed covariates was used for the genetic analysis of frailty to account for censoring and truncation in the lifetime data. During the follow-up, 1437 deaths occurred, including 435 deaths due to CHD. Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best-fitting model without covariates, heritability of frailty to CHD was found to be 0.45 (0.11). This result changes only slightly to 0.55 (0.13) in a DE model after controlling for smoking and BMI. This analysis underlines the existence of a substantial genetic influence on individual frailty associated with mortality caused by CHD.
The Differential Heritability of Regular Tobacco Use Based on Method of Administration
Authors: Schmitt J. Eric , Prescott Carol A. , Gardner Charles O. , Neale Michael C. , Kendler Kenneth S. 
Published: May 2007

AbstractSeveral large studies have demonstrated that the liability to smoke cigarettes is strongly genetically influenced. However, the role of genetic and environmental risk factors in the use of other common forms of tobacco use has yet to be studied. Data on the regular use of cigarettes, cigars, pipes, dip (moist snuff), and chewing tobacco from 2634 male twins were analyzed with ACE structural equation models. Twin similarity for regular cigarette and dip use was largely genetic in origin. However, twin resemblance for chewing tobacco was just about equally the result of genes and shared environment, and twin similarity for use of pipes and cigars was entirely the result of shared environmental factors. Thus, the genetic influences on the liability for regular tobacco use appear to vary based on tobacco type. The causes for the use of different forms of tobacco are complex and worthy of further study.
Genetic and Environmental Influences on Stuttering and Tics in Japanese Twin Children
Authors: Ooki Syuichi 
Published: May 2007

AbstractThe purpose of this study was to clarify the genetic contribution to stuttering and tics in childhood using the largest databases of Japanese twins. The subjects were 1896 pairs of twin children consisting of 1849 males and 1943 females with a mean age of 11.6 years (3 years to 15 years). All data were gathered by questionnaire. The prevalence of stuttering was 6.7% in males and 3.6% in females (p < .0001). The prevalence of tics was 6.8% in males and 4.1% in females (p = .0021). Concordance rates and polychoric correlations were all higher in monozygotic pairs than in dizygotic pairs irrespective of sex combination. Structural equation modeling showed that the proportion of total phenotypic variance attributable to genetic influences was 80% in males and 85% in females for stuttering, and 28% in males and 29% in females for tics. Moreover, co-occurrence between stuttering and tics was observed in 0.8% of males (tetrachoric correlation: r = .18) and 0.5% of females (r = .31), which was attributed partly (nearly 10% of total genetic variance of each trait) to the common genetic factors, with genetic correlation of r = .32.
The Value of Four Mental Health Self-Report Scales in Predicting Interview-Based Mood and Anxiety Disorder Diagnoses in Sibling Pairs
Authors: Williamson Richard J. , Neale Benjamin M. , Sterne Abram , Prince Martin , Sham Pak 
Published: May 2007

AbstractQuestionnaire-based dimensional measures are often employed in epidemiological studies to predict the presence of psychiatric disorders. The present study sought to determine how accurately 4 dimensional mental health measures, the 12-item General Health Questionnaire (GHQ-12), Neuroticism (EPQ-N), the high positive affect and anxious arousal scales from the Mood and Anxiety Symptoms Questionnaire (MASQ-HPA and MASQ-AA) and a composite of all 4, predicted psychiatric caseness as diagnosed by the University of Michigan Composite International Diagnostic Interview (UM-CIDI). Community subjects were recruited through general practitioners; those who agreed to participate were sent a questionnaire containing the above measures. Subsequently, the UM-CIDI was administered by telephone to 469 subjects consisting of sibling pairs who scored most discordantly or concordantly on a composite index of the 4 measures. Logistic Regression and Receiver Operating Characteristic (ROC) curve analyses were carried out to assess the predictive accuracy of the dimensional measures on UM-CIDI diagnosis. A total of 179 subjects, 62 men and 117 women with an average age of 42 years, were diagnosed with at least one of the following psychiatric disorders: depression, dysthymia, generalized anxiety disorder (GAD), social phobia, agoraphobia and panic attack. The six disorders showed high comorbidity. EPQ-N and the Composite Index were found to be very strong and accurate predictors of psychiatric caseness; they were however unable to differentiate between specific disorders. The results from the present study therefore validated the four mental health measures as being predictive of psychiatric caseness.
Where Did I Leave My Keys? A Twin Study of Self-Reported Memory Ratings Using the Multifactorial Memory Questionnaire
Authors: Singer Jamie J. , MacGregor Alex J. , Cherkas Lynn F. , Spector Tim D. 
Published: May 2007

AbstractBehavior genetics has convincingly shown the importance of genetic factors in objective tests of memory function. However, self-report memory tests have received little attention. This study used items from the Multifactorial Memory Questionnaire (MMQ) to estimate the heritability of self-reported memory contentment and ability in 909 monozygotic (MZ) and 1034 dizygotic (DZ) twin pairs aged between 20 and 84 years from the St Thomas' Adult UK Twin Register. Heritability estimates ranged between 37% and 64% for contentment (e.g., reporting to worry about one's memory) and approximately 45% for ability (e.g., reporting a tendency to forget keys). Shared family environmental influences (between 32% and 33%) were found for some abilities (e.g., learning to use a new gadget). Given their clinical significance and ease of administration, these tests could prove to be useful in examining memory functioning in large-scale population studies.
Genetic Factors in Seizures: A Population-Based Study of 47,626 US, Norwegian and Danish Twin Pairs
Authors: Kjeldsen Marianne J. , Corey Linda A. , Solaas Marit H. , Friis Mogens L. , Harris Jennifer R. , Kyvik Kirsten O. , Christensen Kaare , Pellock John M. 
Published: May 2007

AbstractThe purpose of the study was to describe a large sample of twins reporting a history of seizures, to characterize seizures in the three subpopulations, and to estimate the relative importance of genetic and environmental factors in seizure occurrence. Seizure history was determined by questionnaires completed by twins in population-based twin registries in the United States, Norway and Denmark. Concordance rates were calculated for all seizure categories within and across twin populations. Of 47,626 twin pairs evaluated, 6234 reported a history of seizures in one or both twins. Concordance rates were significantly higher for monozygotic (MZ) versus dizygotic (DZ) pairs for all seizure categories within and across populations. The results of this study involving the largest unselected, population-based sample of twins with seizures assembled to date confirm the importance of genetic factors in determining risk for epilepsy, febrile seizures, other seizures and staring spells. This sample is likely to provide an important resource for studying the genetics of epilepsy subtypes and febrile seizures.
The Convergence of the Regional Twinning Rates in Sweden, 1751–1960
Authors: Fellman Johan , Eriksson Aldur W. 
Published: May 2007

AbstractSweden has, as a whole nation, the oldest continuous population register of births, including twin and higher multiple maternities, starting in the 17th century. Until the 1920s, the rates of multiple maternities in Sweden were among the highest known among Europeans. Strong secular and regional fluctuations were noted. Some of the eastern counties showed especially marked decreasing trends. The twinning rate had no clear associations with the anthropometric and serological data. In this paper we study the temporal and regional variations of the twinning rate in the 25 counties of Sweden from 1751 to 1960. Different statistical methods were applied in order to test the hypothesis that, irrespective of the initial levels, the twinning rates for the counties converge towards a common low level. We present and interpret a geometrical model for the trends of the regional twinning rates. We also analyze the regional heterogeneity using the ranges and the coefficients of variation of the regional twinning rates. All the methods gave consistent results, supporting our convergence hypothesis that the regional differences in the twinning rate are gradually disappearing. In addition, this study supports our earlier findings that the regional heterogeneity cannot be explained by differences in the distribution of maternal age and parity. We suggest that the convergence may be caused by increased urbanization and industrialization and by the increased interregional migration of citizens as a consequence of better communications, which lead to the breaking up of isolates and decreased endogamy.
Chimeric Dizygotic Twins; Twin Study Summaries; News At Home and Abroad
Authors: Segal Nancy L. 
Published: May 2007

AbstractChimeras, individuals whose genetically distinct cell lines originated from different zygotes, are attracting attention among twin researchers. This is because chimerism may occur more frequently than previously suspected, having been observed among 8% of dizygotic (DZ) twins and 21% of DZ triplets. The presence of separate cell lines in these twins may hold clues to disease susceptibility, developmental complications and histocompatibility features. Next, new twin research on physical development is offering fresh insights on height and hormones, height and education, and pelvic development. Finally, twins having twins, twins deserting the military and twins composing music raise new thoughts about reproduction, behavior and talent.
Genome-Wide Linkage Disequilibrium from 100,000 SNPs in the East Finland Founder Population
Authors: Uimari Pekka , Kontkanen Outi , Visscher Peter M. , Pirskanen Mia , Fuentes Ricardo , Salonen Jukka T. 
Published: May 2007

AbstractInformation about linkage disequilibrium (LD) is important in understanding the genome structure and has its applications in association studies. Here we present the first genome-wide LD study based on a founder population (East Finland). The LD data consist of 118 unrelated individuals and around 480,000 SNP pairs genotyped with the Affymetrix 100K genotyping assay. Using the minor allele frequency (MAF) limit of .05, the squared correlation coefficient between two loci (r2) was .48, .37, .28, and .20 for distances of 5, 10, 20, and 40 kb respectively. MAF had a significant effect on the mean r2 so that the extent of useful LD (r2 > .3) varied from 17 kb to 80 kb depending on the limit set for the MAF. For D' the effect of MAF was smaller but reflected the possible age of the mutation: SNPs with high MAF had lower D' than those with low MAF. The X chromosome showed higher D' values than autosomes and the extent of useful LD (r2 > .3) was twice as long on the X chromosome than on the autosomes. Based on the results, LD varies across the genome and is correlated to local recombination rate between and within chromosomes. However, the recombination rate does not explain all the variation found in LD. We also report a number of long chromosomal regions where exceptionally high or low LD were detected.