Ahsen, Nicolas von

[["dc.bibliographiccitation.firstpage","310"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International journal of molecular epidemiology and genetics"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Tzvetkov, Mladen"],["dc.contributor.author","Karunajeewa, Harin A."],["dc.contributor.author","Gomorrai, Servina"],["dc.contributor.author","Ura, Alice"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Davis, Timothy M. E."],["dc.contributor.author","Mueller, Ivo"],["dc.contributor.author","Ilett, Kenneth F."],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2019-07-10T08:13:37Z"],["dc.date.available","2019-07-10T08:13:37Z"],["dc.date.issued","2010"],["dc.description.abstract","PURPOSE: A high frequency of previously unknown CYP2D6 alleles have been reported in Oceania populations. Genetic and functional properties of these alleles remain unknown. METHODS: We performed analyses of the genetic variability of CYP2D6 and CYP2C19 genes using AmpliChip genotyping in cohorts from two distinct Papua New Guinea (PNG) populations (Kunjingini, n=88; Alexishafen, n=84) focussing on the genetic characterisation of PNG-specific alleles by re-sequencing. RESULTS: Previously unknown CYP2D6 alleles have population frequencies of 24% (Kunjingini) and 12% (Alexishafen). An allele similar to CYP2D6 1, but carrying the 1661G>C substitution, was the second most frequent CYP2D6 allele (20% Kunjingini and 10% Alexishafen population frequency). Sequencing suggests the CYP2D6 1661G>C allele originated from a cross-over between CYP2D6 1 and 2 and thus is predicted to confer fully active CYP2D6 enzyme. Two additional predicted full activity alleles [1661G>C;4180G>C] and 31G>A were found in the Kunjingini cohort (frequencies 3 c/c and 1%, respectively) and a novel predicted reduced activity allele [100C>T;1039C>T] was found in the Alexishafen cohort (frequency 2%). A high frequency of ultra-rapid (15%) and notably low frequencies of intermediate and poor CYP2D6 metabolizers (<5%) and a high frequency of poor CYP2C19 metabolizers were observed in PNG. Both CYP2D6 and CYP2C19 showed heterozygote excess that may be explained by exogamy and recent introduction of alleles by migration that are yet to reach HWE in relatively isolated populations. CONCLUSION: The CYP2D6 1661 allele common in Oceania may be regarded as functionally equivalent to the full activity CYP2D6 1 allele."],["dc.identifier.fs","576822"],["dc.identifier.pmid","21532842"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6920"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61291"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1948-1756"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","CYP2D6 and CYP2C19 in Papua New Guinea: High frequency of previously uncharacterized CYP2D6 alleles and heterozygote excess."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3325"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","3329"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Petrova, Darinka Todorova"],["dc.contributor.author","Weigand, Sebastian"],["dc.contributor.author","Eberle, Christoph"],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Schmitz, Jessica"],["dc.contributor.author","Schultze, Frank Christian"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Karaus, Michael"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2018-11-07T09:59:29Z"],["dc.date.available","2018-11-07T09:59:29Z"],["dc.date.issued","2015"],["dc.description.abstract","AIM: To compare the number of regulatory T-cells (Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR (qPCR) method in patients suffering from inflammatory bowel disease (IBD). METHODS: Tregs percentages obtained by both flow cytometry and qPCR methods in 35 adult IBD patients, 18 out of them with Crohn's disease (CD) and 17 with ulcerative colitis (UC) were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index (HBI) for CD patients and the Simple Colitis Clinical Activity Index (SCCAI) for UC patients. The Treg percentages by flow cytometry were defined as CD4(+)CD25(high)CD127(low)FOXP3(+) cells in peripheral blood mononuclear cells, whereas the Treg percentages by qPCR method were determined as FOXP3 promoter demethylation in genomic DNA. RESULTS: We found an average of 1.56% +/- 0.78% Tregs by using flow cytometry, compared to 1.07% +/- 0.53% Tregs by using qPCR in adult IBD patients. There were no significant correlations between either the percentages of Tregs measured by flow cytometry or qPCR and the HBI or SCCAI questionnaire scores in CD or UC patients, respectively. In addition, there was no correlation between Treg percentages measured by qPCR and those measured by flow cytometry (r = -0.06, P = 0.73; Spearman Rho). These data suggest that, either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity. Until the cause(s) for these differences are more clearly defined, the results suggest caution in interpreting studies of Tregs in various inflammatory disorders. CONCLUSION: The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays."],["dc.description.sponsorship","Medical Faculty of the University of Goettingen, Germany"],["dc.identifier.doi","10.3748/wjg.v21.i11.3325"],["dc.identifier.isi","000351165100021"],["dc.identifier.pmid","25805940"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11750"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37598"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publishing Group Inc"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Lack of correlation between Treg quantification assays in inflammatory bowel disease patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","434825"],["dc.bibliographiccitation.journal","Mediators of Inflammation"],["dc.contributor.author","Misdaq, Misbah"],["dc.contributor.author","Ziegler, Sonia"],["dc.contributor.author","Ahsen, Nicolas von"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2018-11-07T10:03:25Z"],["dc.date.available","2018-11-07T10:03:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Thiopurines are extensively used immunosuppressants for the treatment of inflammatory bowel disease (IBD). The polymorphism of thiopurine S-methyltransferase (TPMT) influences thiopurine metabolism and therapy outcome. We used a TPMT knockdown (kd) model of human Jurkat T-lymphocytes cells to study the effects of treatment with 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) on proteome and phosphoproteome. We identified thirteen proteins with altered expression and nine proteins with altered phosphorylation signals. Three proteins (THIO, TXD17, and GSTM3) with putative functions in cellular oxidative stress responses were altered by 6-TG treatment and another protein PRDX3 was differentially phosphorylated in TPMT kd cells. Furthermore, reactive oxygen species (ROS) assay results were consistent with a significant induction of oxidative stress by both TPMT knockdown and thiopurine treatments. Immunoblot analyses showed treatment altered expression of key antioxidant enzymes (i.e., SOD2 and catalase) in both wt and kd groups, while SOD1 was downregulated by 6-TG treatment and TPMT knockdown. Collectively, increased oxidative stress might be a mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e., hepatotoxicity) and an antioxidant cotherapy might help to combat this. Results highlight the significance of oxidative stress in thiopurines' actions and could have important implications for the treatment of IBD patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1155/2015/434825"],["dc.identifier.isi","000352444800001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38460"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1466-1861"],["dc.relation.issn","0962-9351"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]