TY  - JOUR
A1  - Bousquet, J.
A1  - Anto, J. M.
A1  - Akdis, M.
A1  - Auffray, C.
A1  - Keil, T.
A1  - Momas, I.
A1  - Postma, D. S.
A1  - Valenta, R.
A1  - Wickman, M.
A1  - Cambon-Thomsen, A.
A1  - Haahtela, T.
A1  - Lambrecht, B. N.
A1  - Lodrup Carlsen, K. C.
A1  - Koppelman, G. H.
A1  - Sunyer, J.
A1  - Zuberbier, T.
A1  - Annesi-Maesano, I.
A1  - Arno, A.
A1  - Bindslev-Jensen, C.
A1  - De Carlo, G.
A1  - Forastiere, F.
A1  - Heinrich, J.
A1  - Kowalski, M. L.
A1  - Maier, D.
A1  - Melen, E.
A1  - Palkonen, S.
A1  - Smit, H. A.
A1  - Standl, M.
A1  - Wright, J.
A1  - Asarnoj, A.
A1  - Benet, M.
A1  - Ballardini, N.
A1  - Garcia-Aymerich, J.
A1  - Gehring, U.
A1  - Guerra, S.
A1  - Hohman, C.
A1  - Kull, I.
A1  - Lupinek, C.
A1  - Pinart, M.
A1  - Skrindo, I.
A1  - Westman, M.
A1  - Smagghe, D.
A1  - Akdis, C.
A1  - Albang, R.
A1  - Anastasova, V.
A1  - Anderson, N.
A1  - Bachert, C.
A1  - Ballereau, S.
A1  - Ballester, F.
A1  - Basagana, X.
A1  - Bedbrook, A.
A1  - Bergstrom, A.
A1  - von Berg, A.
A1  - Brunekreef, B.
A1  - Burte, E.
A1  - Carlsen, K.H.
A1  - Chatzi, L.
A1  - Coquet, J.M.
A1  - Curin, M.
A1  - Demoly, P.
A1  - Eller, E.
A1  - Fantini, M.P.
A1  - Gerhard, B.
A1  - Hammad, H.
A1  - von Hertzen, L.
A1  - Hovland, V.
A1  - Jacquemin, B.
A1  - Just, J.
A1  - Keller, T.
A1  - Kerkhof, M.
A1  - Kiss, R.
A1  - Kogevinas, M.
A1  - Koletzko, S.
A1  - Lau, S.
A1  - Lehmann, I.
A1  - Lemonnier, N.
A1  - McEachan, R.
A1  - Makela, M.
A1  - Mestres, J.
A1  - Minina, E.
A1  - Mowinckel, P.
A1  - Nadif, R.
A1  - Nawijn, M.
A1  - Oddie, S.
A1  - Pellet, J.
A1  - Pin, I.
A1  - Porta, D.
A1  - Rancière, F.
A1  - Rial-Sebbag, A.
A1  - Schuijs, M.J.
A1  - Siroux, V.
A1  - Tischer, C.G.
A1  - Torrent, M.
A1  - Varraso, R.
A1  - De Vocht, J.
A1  - Wenger, K.
A1  - Wieser, S.
A1  - Xu, C.
T1  - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story 
Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015
JF  - Allergy
N2  - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.
KW  - asthma
KW  - birth cohort
KW  - atopic-dermatitis
KW  - immune-responses
KW  - IgE
KW  - multimorbidity
KW  - polysensitization
KW  - rhinitis
KW  - chronic respiratory-diseases
KW  - childhood asthma
KW  - immunological reactivity
KW  - IgE sensitazion
KW  - immunoglobulin-e
KW  - integraed care
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858
VL  - 71
IS  - 11
ER  - 
TY  - JOUR
A1  - Sommer, Claudia
A1  - Richter, Helmut
A1  - Rogausch, Jan P.
A1  - Frettloh, Jule
A1  - Lungenhausen, Margitta
A1  - Maier, Christoph
T1  - A modified score to identify and discriminate neuropathic pain: a study on the German version of the neuropathic pain symptom inventory (NPSI)
N2  - Background: Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain. Methods: We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles. Results: Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct. Conclusions: The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.
KW  - Neuralgie
KW  - NPSI
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68716
ER  - 
TY  - JOUR
A1  - Kugler-Steigmeier, M. E.
A1  - Friederich, U.
A1  - Graf, U.
A1  - Lutz, Werner K.
A1  - Maier, P.
A1  - Schlatter, C.
T1  - Genotoxicity of aniline derivatives in various short-term tests
N2  - Various substituted aniline derivatives were tested for genotoxicity in several short-term tests in order to examine the hypothesis that a Substitution at both ortho positions (2,6-disubstitution) could prevent genotoxicity due to steric hindrance of an enzymatic activation to electrophilic intermediates. In the Salmonellajmicrosome assay, 2,6-dialkylsubstituted anilines and 2,4,6-trimethylaniline (2,4,6-TMA) were weakly mutagenic in strain TA100 when 20% S9 mixwas used, although effects were small compared to those of 2,4-dimethylaniline and 2,4,5-trimethylaniline (2,4,5-TMA). In Drosophila me/anogaster, however, 2,4,6-TMA and 2,4,6-trichloroaniline (TCA) were mutagenic in the wing spottestat 2-3 times lower doses than 2,4,5-TMA. In the 6-thioguanine resistance test in cultured fibroblasts, 2,4,6-TMA was again mutagenic at lower doses than 2,4,5-TMA. Two methylene-bis-aniline derivatives were also tested with the above methods: 4,4'-methylene-bis-(2-chloroaniline) (MOCA) was moderately genotoxic in al1 3 test systems whereas 4,4'-methylene-bis-(2-ethyl-6-methylaniline) (MMEA) showed no genotoxicity at all. DNA binding sturlies in rats, however, revealed that both MOCA and MMEA produced DNA adducts in the liver at Ievels typically found for moderately strong genotoxic carcinogens. These results indicate that the predictive value of the in vitro test systems and particularly the Salmonellajmicrosome assay is inadequate to detect genotoxicity in aromatic amines. Genotoxicity seems to be a general property of aniline derivatives and does not seem to be greatly influenced by substitution at both ortho positions.
KW  - Toxikologie
KW  - Aniline derivatives
KW  - Genotoxicity
KW  - Short-term tests
KW  - Covalent DNA binding
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60857
ER  - 
TY  - JOUR
A1  - Lutz, Werner K.
A1  - Maier, P.
T1  - Genotoxic and epigenetic chemical carcinogenesis: one process, different mechanisms
N2  - Chemieals that induce cancer in an intact organism are called carcinogens. This term does not differentiale between their various modes of action. In this review, Werner Lutz and Peter Maier make a mechanistic distinction between carcinogens that alter the genetic information and carcinogens that interfere with epigenetic processes. They considercardnogenesis tobe an ongoing, part1y unavoidable process which is based on a succession of mutations, most likely in stem cells, leading to autonomaus cellular growth regulation. Chemical carcinogens either induce such changes through mutations (genotoxic carcinogens) or they aceeierate the accumulation of critica1 spontaneaus mut11tions (epigenetic carcinogens). Examples are given for both classes of carcinogens, and for the processes that act at genoto:tic/nuclear 11nd epigenetic/mitotic Ievels.
KW  - Toxikologie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60884
ER  - 
TY  - JOUR
A1  - Haferkamp, Sebastian
A1  - Hesbacher, Sonja
A1  - Weyandt, Gerhard
A1  - Vetter-Kauczok, Claudia S.
A1  - Becker, Jürgen C.
A1  - Motschenbacher, Stephanie
A1  - Wobser, Marion
A1  - Maier, Melissa
A1  - Schmid, Corinna P.
A1  - Houben, Roland
T1  - p53 regulation by TRP2 is not pervasive in melanoma
N2  - p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma.
KW  - melanomas
KW  - melanoma cell
KW  - cell staining
KW  - histology
KW  - reporter genes
KW  - apoptosis
KW  - immunohistochemistry techniques
KW  - tumor suppressor genes
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111396
ER  - 
TY  - JOUR
A1  - Weber, Heike
A1  - Scholz, Claus Jürgen
A1  - Domschke, Katharina
A1  - Baumann, Christian
A1  - Klauke, Benedikt
A1  - Jacob, Christian P.
A1  - Maier, Wolfgang
A1  - Fritze, Jürgen
A1  - Bandelow, Borwin
A1  - Zwanzger, Peter Michael
A1  - Lang, Thomas
A1  - Fehm, Lydia
A1  - Ströhle, Andreas
A1  - Hamm, Alfons
A1  - Gerlach, Alexander L.
A1  - Alpers, Georg W.
A1  - Kircher, Tilo
A1  - Wittchen, Hans-Ulrich
A1  - Arolt, Volker
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Reif, Andreas
T1  - Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder
N2  - Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75830
ER  - 
TY  - JOUR
A1  - Dumont, Martine
A1  - Weber-Lassalle, Nana
A1  - Joly-Beauparlant, Charles
A1  - Ernst, Corinna
A1  - Droit, Arnaud
A1  - Feng, Bing-Jian
A1  - Dubois, Stéphane
A1  - Collin-Deschesnes, Annie-Claude
A1  - Soucy, Penny
A1  - Vallée, Maxime
A1  - Fournier, Frédéric
A1  - Lemaçon, Audrey
A1  - Adank, Muriel A.
A1  - Allen, Jamie
A1  - Altmüller, Janine
A1  - Arnold, Norbert
A1  - Ausems, Margreet G. E. M.
A1  - Berutti, Riccardo
A1  - Bolla, Manjeet K.
A1  - Bull, Shelley
A1  - Carvalho, Sara
A1  - Cornelissen, Sten
A1  - Dufault, Michael R.
A1  - Dunning, Alison M.
A1  - Engel, Christoph
A1  - Gehrig, Andrea
A1  - Geurts-Giele, Willemina R. R.
A1  - Gieger, Christian
A1  - Green, Jessica
A1  - Hackmann, Karl
A1  - Helmy, Mohamed
A1  - Hentschel, Julia
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hooning, Maartje J.
A1  - Horváth, Judit
A1  - Ikram, M. Arfan
A1  - Kaulfuß, Silke
A1  - Keeman, Renske
A1  - Kuang, Da
A1  - Luccarini, Craig
A1  - Maier, Wolfgang
A1  - Martens, John W. M.
A1  - Niederacher, Dieter
A1  - Nürnberg, Peter
A1  - Ott, Claus-Eric
A1  - Peters, Annette
A1  - Pharoah, Paul D. P.
A1  - Ramirez, Alfredo
A1  - Ramser, Juliane
A1  - Riedel-Heller, Steffi
A1  - Schmidt, Gunnar
A1  - Shah, Mitul
A1  - Scherer, Martin
A1  - Stäbler, Antje
A1  - Strom, Tim M.
A1  - Sutter, Christian
A1  - Thiele, Holger
A1  - van Asperen, Christi J.
A1  - van der Kolk, Lizet
A1  - van der Luijt, Rob B.
A1  - Volk, Alexander E.
A1  - Wagner, Michael
A1  - Waisfisz, Quinten
A1  - Wang, Qin
A1  - Wang-Gohrke, Shan
A1  - Weber, Bernhard H. F.
A1  - Devilee, Peter
A1  - Tavtigian, Sean
A1  - Bader, Gary D.
A1  - Meindl, Alfons
A1  - Goldgar, David E.
A1  - Andrulis, Irene L.
A1  - Schmutzler, Rita K.
A1  - Easton, Douglas F.
A1  - Schmidt, Marjanka K.
A1  - Hahnen, Eric
A1  - Simard, Jacques
T1  - Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
JF  - Cancers
N2  - Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
KW  - breast cancer
KW  - genetic susceptibility
KW  - whole-exome sequencing
KW  - moderate-penetrance genes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281768
SN  - 2072-6694
VL  - 14
IS  - 14
ER  - 
TY  - JOUR
A1  - Krüger, H.-P.
A1  - Bonerad, E. M.
A1  - Dennler, H. J.
A1  - Dunkl, E.
A1  - Friese, H. J.
A1  - Hain, C.
A1  - Kazenwadel, J.
A1  - Kohnen, Ralf
A1  - Maier, W.
A1  - Menzel, M.
T1  - Speech chronemics in drug evaluation
N2  - No abstract available
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-41213
ER  -