Biomedical subjects

Stephan K Weiland

Publications and source records attributed to Stephan K Weiland.

25 records · Page 2Linked to original sources

PubMed2003

Positional cloning of a novel gene influencing asthma from chromosome 2q14.

Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy.

Amino Acid Sequence↗

PubMed2003

A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood.

BACKGROUND: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5' untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. OBJECTIVE: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. METHODS: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. RESULTS: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. CONCLUSION: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.

Asthma↗

PubMed2003

Smoking among adolescents in Muenster, Germany: increase in prevalence (1995-2000) and relation to tobacco advertising.

BACKGROUND: Understanding patterns and trends of smoking among youths is of major importance for the assessment of the burden of smoking in the society and efforts to decrease it. OBJECTIVE: The aims were to determine the prevalence and trends of smoking among adolescents in Muenster, Germany, and to assess its relation to youths' awareness of tobacco advertisement. DESIGN: Information on smoking habits was collected during two school-based surveys (1994/1995 and 1999/2000) of 12- to 15-year-old adolescents (3934 students in 1994/5 and 4028 students in 1999/2000) in Muenster, Germany. In addition, in 1994/1995 information about youths' awareness and appreciation of tobacco advertisement was collected. RESULTS: During the 5-year period, the prevalence of current smoking increased from 21.3 to 28.3%, and daily smoking increased from 10.0 to 14.2%. Among girls, daily smoking increased by 62% during this period. Almost all participants (94%) in 1994/1995 knew a tobacco brand, and appreciation of tobacco advertisement was strongly associated with the frequency of smoking. CONCLUSION: Smoking is increasing among adolescents in Germany especially among girls. These data are a cause of concern and call for efforts to reverse these trends, which should include a ban on tobacco advertisement in Germany.

Adolescent↗

PubMed2003

Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations.

BACKGROUND: Early exposure to microbial matter such as LPS may influence the development of asthma and allergies by activation of innate immunity pathways as indicated by studies in farming environments. Recently, polymorphisms in caspase recruitment domain containing protein 15 (CARD15), an intracellular LPS receptor protein, have been associated with Crohn's disease. Because these polymorphisms lead to changes in LPS recognition, they may affect the development of asthma and allergies. OBJECTIVE: We genotyped a large population of German schoolchildren (N = 1872) from East and West Germany for 3 functional relevant CARD15 polymorphisms for their role in the development of asthma and allergy. METHODS: By use of parental questionnaires, skin prick testing, pulmonary function tests, bronchial challenge tests, and measurements of serum IgE levels, children were phenotyped for the presence of atopic diseases. Genotyping was performed with PCR-based restriction enzyme assays. To assess associations between atopic phenotypes and genotypes standard statistical procedures were applied. RESULTS: Children with the polymorphic allele C2722 had a more than 3-fold risk to develop allergic rhinitis (P <.001) and an almost 2-fold risk for atopic dermatitis (P <.05). Furthermore, the T2104 allele was associated with an almost 2-fold risk for allergic rhinitis (P <.05). When a C insertion at position 3020 was present, the risk of atopy increased by 50% (P <.05) and serum IgE levels were elevated (P <.01). CONCLUSION: The shared genetic background between Crohn's disease and atopy may indicate that an impaired recognition of microbial exposures results in an insufficient downregulation of excessive immune responses, giving rise to either T(H)2 dominated allergies or T(H)1 related Crohn's disease.

Carrier Proteins↗

PubMed2003

Job titles and work areas as surrogate indicators of occupational exposure.

BACKGROUND: Job titles or work areas are often used as surrogate indicators of exposure in occupational epidemiological studies. In this article, we assess the validity and comparability of commonly used surrogate indicators. METHODS: We analyzed lung cancer mortality among a hypothetical and an actual cohort of rubber workers. Surrogate indicators of exposure were defined according to jobs in which workers were "only," "ever," "longest" or "last" employed, or in which they were employed at the "census" of the study. Occupational risks were estimated using standardized mortality ratios. Validity of surrogate indicators was assessed in the simulated data by comparison between estimated effects and the known underlying associations. Comparisons of surrogate indicators were conducted in both simulated and empirical data. RESULTS: Use of the definition "only" as the surrogate indicator gave valid but imprecise results. For all other definitions, we observed a moderate overestimation of risks in no-risk or low-risk jobs and attenuation of underlying dose-response relationships, without substantial differences among the applied definitions. CONCLUSIONS: Our results demonstrate a limitation of using surrogate indicators of exposure in occupational epidemiological studies. However, they suggest that the inconsistencies of published study findings in the rubber industry are unlikely to be attributable to the use of different surrogate indicators.

Cohort Studies↗

PubMed2002

[Validation and subjective reports of exposure to traffic by traffic count, NO2 dispersion modeling and measuring NO2 emissions].

OBJECTIVES: The validity of self-reports of traffic density on street of residence in cities has not been evaluated extensively yet. METHODS: This study compared traffic self-reports with exposure estimates based on traffic counts and emission measurements. RESULTS: Self-reports correlated well with traffic count data but less well with data from measurements of background emission. CONCLUSIONS: As traffic counts primarily represent direct exposure to road traffic and emission concentrations primarily represent city background exposure to traffic-related pollutants, self-reports reflect direct traffic exposure more strongly than background exposure.

Air Pollutants↗

PubMed2002

T(H)1/T(H)2 immune response profiles differ between atopic children in eastern and western Germany.

BACKGROUND: Lower prevalence rates for childhood respiratory allergies have been reported in eastern Germany than in western Germany. OBJECTIVE: Because allergic phenotypes are thought to be associated with an unbalanced T(H)1/T(H)2 T cell effector response, a cross-sectional investigation was carried out as part of the German ISAAC Phase II study to determine whether T(H)1/T(H)2 capacity might have developed in different directions during the separation between the 2 parts of the country. METHODS: In a community-based random sample of 9- to 11-year-old (n = 6399) and 5- to 7-year-old (n = 6202) children in eastern and western Germany, the prevalence of atopy was assessed. Heparinized blood samples were collected from a subgroup of children stratified according to the number of older siblings. T(H)1 and T(H)2 cytokine productivity was determined after stimulation with phorbol ester plus ionomycin. RESULTS: Individuals who grew up in eastern Germany had a marked bias toward T(H)0 responsiveness (>60%), regardless of whether they were atopic. In contrast, the children of western Germany, particularly when they were atopic, showed T(H)2 polarization. CONCLUSIONS: This is the first epidemiologic survey to demonstrate regional differences in the T(H)1/T(H)2 response pattern and their relation to atopic disease between regions.

Asthma↗