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  • 1
    Electronic Resource
    Electronic Resource
    A mathematical approach to benzo[a]pyrene-induced hematotoxicity (1992)
    Springer
    Archives of toxicology 66 (1992), S. 546-550 
    Details
    ISSN: 1432-0738
    Keywords: Benzo[a]pyrene ; Mathematical model ; Hematopoiesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Benzo[a]pyrene (BaP) has been reported to exert a differential effect on murine hematopoiesis that is mouse strain specific. Interpretation of these results based solely on experimental data is restricted and leaves important questions unanswered. Therefore, a mathematical model of murine hematopoiesis was applied in order to: (1) identify the targets of BaP, (2) quantify the damage to target cells and (3) based on these results, interpret differences in strain susceptibility. Model analysis of the hematopoietic response of D2 and BDF1 mice to a daily oral administration of 125 mg/kg BaP showed that proliferating hematopoietic cells are the targets of BaP. Within this group it was found that: (a) erythropoietic cells were the most susceptible to BaP, (b) granulopoietic cells showed a susceptibility half that of erythropoietic cells and (c) the susceptibility of stem cells ranged between that of erythropoietic and granulopoietic cells. This damage pattern was the same for both strains, indicating that the difference between the strains was quantitative. As cell destruction rates were about 3-fold higher for D2 than BDF1 mice, it was concluded that D2 mice were about three times as susceptible to BaP as BDF1 mice. The study showed that the mathematical model, in addition to experimental methods, provided an efficient tool for the analysis of BaP hematotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973384
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  • 2
    Electronic Resource
    Electronic Resource
    Multiple Testing for SNP-SNP Interactions (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Statistical applications in genetics and molecular biology 6.2007, 1, art37 
    Details
    ISSN: 1544-6115
    Source: Berkeley Electronic Press Academic Journals
    Topics: Biology
    Notes: Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustments when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/sagmb/vol6/iss1/art37
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  • 3
    Electronic Resource
    Electronic Resource
    Hay fever and predictive value of prick test and specific IgE antibodies: A prospective study in children (2003)
    Oxford, UK : Munksgaard International Publishers
    Pediatric allergy and immunology 14 (2003), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Little is known from population-based studies in children about the diagnostic values of allergen-specific IgE antibodies (RAST) and skin prick test (SPT) with respect to hay fever. We aimed to determine and compare the diagnostic values of SPT and RAST to aeroallergens with respect to the incidence of hay fever cases in schoolchildren at different cut-off points. A prospective cohort study was performed on 1100 school children (5–7 and 8–10 years). Information on a doctor's diagnosis of hay fever was obtained by questionnaire and allergic sensitization to grass and birch pollen, cat, and Dermatophagoides pteronyssinus were measured using SPT and RAST between September 1992 and July 1993. Thirty-eight children give a history of hay fever (3.5%) in 1992/93 and additionally 37 cases occurred until 1996. Allergic sensitization was present in 17.9% (SPT), 30.2% (RAST) and more frequent in children with a history of hay fever (SPT: OR 11.7, 5.5–24.7; RAST: OR 10.6, 4.3–26.4). This difference was most pronounced for sensitization to pollen allergens. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) for SPT and RAST were 65.6, 83.7, 11.9, 98.6 and 79.3, 71.6, 9.3, 99.0, respectively, with differences for specificity being significant (p 〈 0.001). Whereas NPV were equally high for SPT (99.2) and RAST (99.3), the incidence of hay fever cases were predicted rather poorly though somewhat better by SPT than by RAST (PPV 16.7 vs. 9.8; p 〈 0.001) initially. With increasing cut-off point for RAST reactivity, the PPV increased and reached 25.0 at 17.5 kU/l, whereas the NPV decreased to 97.9, which was lower than that of SPT reactivity (p 〈 0.01). At the cut-off point of 1.5 kU/l almost identical predictive values for SPT and RAST were obtained. SPT and RAST perform better in the negative than positive prediction of hay fever cases in epidemiological studies. Differences in the predictive capabilities depend on the chosen cut-off point for RAST reactivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1399-3038.2003.00024.x
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  • 4
    Electronic Resource
    Electronic Resource
    Exposure to pets and atopic dermatitis during the first two years of life. A cohort study (2002)
    Berlin, Germany : Munksgaard International Publishers
    Pediatric allergy and immunology 13 (2002), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to assess the association between keeping pets in early childhood and the occurrence of atopic dermatitis in an ongoing birth cohort followed up to the age of 2 years. We analyzed data of 4578 children in the intervention and observation part of an ongoing cohort study. The children were recruited at birth in the two study regions Wesel and Munich between January 1996 and June 1998. Information on atopic diseases and pet ownership was obtained by questionnaire at the child's first and second birthday. The logistic regression model showed a negative association between ‘keeping any pet’ and in particular ‘keeping dogs’ in the 1st year of life and the development of atopic dermatitis in the 1st and the 2nd years of life. The protective effects remained statistically significant after adjusting for several possible confounding variables (1st yearany pet OR 0.71, 95% CI [0.55;0.92], 1st yeardog OR 0.62, 95% CI [0.39;0.98], 2nd yearany pet OR 0.74, 95% CI [0.57;0.97], 2nd yeardog OR 0.63, 95% CI [0.40;0.98]). Ownership of small furred pets (hamster, rabbit and guinea pig) also showed a borderline protective effect for the 1st year. We assume an association between keeping pets and undefined environmental factor(s) that contribute protectively to the development of atopic dermatitis in early life, presumably by effects on the maturation of the immune system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1399-3038.2002.01110.x
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  • 5
    Electronic Resource
    Electronic Resource
    Exposure to pets and allergies in children (2002)
    Copenhagen, Denmark : Munksgaard International Publishers
    Pediatric allergy and immunology 13 (2002), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Currently, there is ongoing discussion regarding potential protective effects of exposure to pets during early childhood on the development of atopic disorders in children later in life. We used data from three consecutive cross-sectional surveys to study the relationship between contact with dogs, cats and other pets, and allergic diseases in schoolchildren 5–14 years of age. In three study areas of the former East Germany, 7,611 questionnaires were received from 5,360 different children who were examined between 1992 and 1999 as school entrants, or third- or sixth-graders. Allergic sensitization to common aeroallergens (birch, grass, mite, cat) was assessed by specific serum immunoglobulin E (IgE) concentrations [using radioallergosorbent testing (RAST)] for 85% of the children. After adjustment for possible confounders, inverse associations were found between contact with dogs in the first year of life and lifetime prevalences of asthma [odds ratio (OR) = 0.68; 95% confidence interval (CI): 0.43–1.08], hay fever (OR = 0.61; 95% CI: 0.39–0.95), eczema (OR = 0.76; 95% CI: 0.61–0.94), itchy rash (OR = 0.76; 95% CI: 0.61–0.94), and pollen sensitization (RAST ≥ 4: OR = 0.56; 95% CI: 0.38–0.82). These effects were more pronounced for children with atopic parents. Similar associations were observed for current contact with dogs. We identified no clear relationships for the other pets (cats, rodents, birds), with the exception that children currently exposed to cats were more likely to be sensitized against cats. In conclusion, this study supports the hypothesis of a potential protective mechanism related to dog exposure in early life, especially for children of atopic parents. However, this association was found only for dogs and not for cats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1399-3038.2002.02063.x
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  • 6
    Electronic Resource
    Electronic Resource
    Mode of delivery and development of atopic disease during the first 2 years of life (2004)
    Oxford, UK : Munksgaard International Publishers
    Pediatric allergy and immunology 15 (2004), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been hypothesized that cesarean delivery might have an impact on the development of atopic diseases because of its gut flora modulating properties. In the present study, we analysed the association between cesarean delivery and atopic diseases using data of 2500 infants enrolled in the LISA-Study, a German prospective multicenter birth cohort study. Data on symptoms and physician-diagnosed atopic diseases were gathered by questionnaires shortly after birth and at infant's age 6, 12, 18, and 24 months. In addition, sensitization to common food and inhalant allergens was assessed by measuring specific immunoglobulin E (IgE) using the CAP-RAST FEIA method at the age of 2 yr. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. We found a positive association between cesarean delivery and occurrence of at least one episode of wheezing [aOR 1.31 (95% CI 1.02–1.68)] and of recurrent wheezing [1.41 (1.02–1.96)] during the first 2 yr of life. Furthermore, effect estimates for allergic sensitization defined as at least one specific IgE ≥0.70 kU/l against any allergen [1.48 (0.98–2.24)], against food allergens [1.64 (1.03–2.63)], and against inhalant allergens [1.75 (0.98–3.12)] were increased. Symptoms of atopic dermatitis [1.21 (0.92–1.59)], physician-diagnosed atopic dermatitis [1.04 (0.79–1.39)], and symptoms of allergic rhinoconjunctivitis [1.40 (0.80–2.44)] were only marginally increased in children delivered by cesarean section. In conclusion, our results suggest that cesarean delivery may be an additional risk factor for wheezing and allergic sensitization at least to food allergens up to the age of 2 yr. This should be considered when cesarean section is done for other than medical reasons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0905-6157.2003.00101.x
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  • 7
    Electronic Resource
    Electronic Resource
    Pulmonary function in children with initial low birth weight (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Pediatric allergy and immunology 9 (1998), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The objective of this analysis was to examine the effect of low birth weight and prematurity on bronchial air-flow, bronchial reactivity, airway symptoms and asthma diagnosis at school age. A cross-sectional epidemiologi-cal study was performed in three small towns in the eastern part of Germany on 2470 school children aged 5–14 (89.1% of eligible children). A 78 item questionnaire to determine risk factors at birth and in early childhood was employed. 7.8% of the children were born before completing 38 gesta-tional weeks; 6.6% had a birth weight less than 2500 g. Pulmonary function analysis were done by a mobile plethysmography at the school. There were only weak restrictions in lung volume in term low birth weight (LBW) children (100 ml lower TLC, p = 0.107), and flow (257 ml lower PEFR, p=0.108), were low. However, bronchial hyper-responsiveness indicated by 292 ml lower FEV1.0 after cold air bronchial provocation, was significantly increased compared to term normal birth weight children (p 〈 0.001). The effect of LBW was less in older children, only slightly stronger in girls and increased in children mechanically ventilated during the postnatal period. Correspondingly, there was a higher prevalence of diagnosed asthma in term LBW children (OR 1.6, 95%-confidence interval 1.0–2.6), however these were without an increased risk for any allergic sensitization. LBW, therefore, seems to be a risk factor for smaller lungs and hyperreactive airways primarily in term born children, whereas in pre-term children the immature bronchial system seems to be recover by school age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1399-3038.1998.tb00308.x
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age (2002)
    Copenhagen, Denmark : Munksgaard International Publishers
    Pediatric allergy and immunology 13 (2002), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis (AD) in infancy. This study is part of a dietary clinical trial in a prospective cohort of healthy term newborns at risk of atopy. It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period. Eight hundred and sixty-five infants exclusively breast-fed, and 256 infants partially or exclusively formula-fed, were followed-up until the end of the first year following birth. AD and sensitization to milk and egg were considered as study end-points. The 1-year incidence of AD was compared between the two study groups. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given. In the breast-fed group, the adjusted OR for AD was 0.47 (95% CI 0.30–0.74). The strongest risk factor was the occurrence of AD in the subject's core family. The risk of infants with AD to be sensitized to milk was four times higher, and to egg eight times higher, than in infants without AD. Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence. We conclude that in infants at atopic risk, exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1399-3038.2002.01050.x
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  • 9
    Electronic Resource
    Electronic Resource
    Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions (2007)
    [s.l.] : Nature Publishing Group
    Nature genetics 39 (2007), S. 1000-1006 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng2099
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  • 10
    Electronic Resource
    Electronic Resource
    A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization (2006)
    [s.l.] : Nature Publishing Group
    Nature genetics 38 (2006), S. 644-651 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng1790
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