TY - JOUR A1 - Schrewe, L. A1 - Lill, C. M. A1 - Liu, T. A1 - Salmen, A. A1 - Gerdes, L. A. A1 - Guillot-Noel, L. A1 - Akkad, D. A. A1 - Blaschke, P. A1 - Graetz, C. A1 - Hoffjan, S. A1 - Kroner, A. A1 - Demir, S. A1 - Böhme, A. A1 - Rieckmann, P. A1 - El Ali, A. A1 - Hagemann, N. A1 - Hermann, D. M. A1 - Cournu-Rebeix, I. A1 - Zipp, F. A1 - Kümpfel, T. A1 - Buttmann, M. A1 - Zettl, U. K. A1 - Fontaine, B. A1 - Bertram, L. A1 - Gold, R. A1 - Chan, A. T1 - Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS JF - Journal of Neuroinflammation N2 - Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods: MOG\(_{35-55}\) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE\(^{-/-}\)) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE\(^{-/-}\) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease. KW - immune KW - apoE KW - gender KW - inflammation KW - association studies in genetics KW - apoe KW - CNS disease KW - system KW - multiple sclerosis KW - MSSS KW - experimental autoimmune encephalomyelitis KW - disease severity KW - cognitive function KW - Alzheimer disease Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136252 VL - 12 IS - 234 ER - TY - CHAP A1 - Krüger, Hans-Peter A1 - Gold, Rainer A1 - Hüppe, A. T1 - Coergisms between drugs and alcohol - a psychopharmacological review N2 - No abstract available. KW - Rauschgift KW - Alkohol Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69850 ER - TY - JOUR A1 - Opwis, K. A1 - Gold, A. A1 - Schneider, Wolfgang T1 - Möglichkeiten der Kreuzvalidierung von Strukturgleichungsmodellen T1 - Cross-validating structural equation models: Problems and perspectives T1 - Possibilites de validation croisee pour des modeles d'equation structurale N2 - Die Beurteilung der Angemessenheit theoretischer Oberlegungen auf der Grundlage statistischer Hypothesentests ist für die empirische Forschung von zentraler Bedeutung. Im Mittelpunkt der Arbeit stehen die mit der Testung von multivariaten Strukturgleichungsmodellen (LISREL-Modelle) verbundenen Probleme. Zu Beginn wird das LISREL-Modell unter den Aspekten der simultanen Analyse von Kovarianzund Mittelwertstrukturen und der Modelltestung diskutiert. Anschließend werden anhand eines Illustrationsbeispiels aus der pädagogisch-psychologischen Forschung verschiedene Vorgehensweisen der Kreuzvalidierung einander gegenübergestellt und an empirischen Daten demonstriert. Es zeigt sich, daß die Obernahme exakter numerischer Parameterwerte sowohl aufgrund inhaltlicher wie auch formaler Argumente unangemessen streng erscheint. Diese Einschätzung kann empirisch belegt werden, indem eine Approximation von Intervallrestriktionen vorgenommen wird. N2 - This study focuses on the problem of how to judge the adequacy of theoretical models on the basis of statistical hypothesis testing procedures. In particular, problems of testing multivariate structural equation models (LISREL-models) are discussed. In a first step, the possibilities of simultaneously analyzing covariance and mean structures and of testing LISREL models are discussed . Next, data from a study conducted in the field of educational psychology are used to illustrate different procedures of cross-validating LISREL models. As it turns out, the usual restriction to base the model on equivalent numerical parameter values appears to be inappropriately rigorous. Thus, the suggestion is that cross-validations of structural equation models should rely on approximations of interval restrictions instead. N2 - Le jugement de l'appropriation des modeles theoriques base sur des tests d'hytheses statistiques est d'une importance capitale pour la recherche empirique . Les problemes lies a la verification de modeJes muJtivariants d'equation structurale sont au cen tre de cette etude. On trouve pour commencer une discussion sur le modele LISREL sous l'aspect de l'analyse simultanee de structures de covariance et de valeur moyenne et sous celui de la verification du modele. Suit ne comparaison de differents procedes de validation croiée. demontree d'apres des donnees empiriques et illustree par des exemples pris dans Ja recherche psychopedagogique. Il en ressort que la reprise de parametres numeriques exacts parait inadequate dans sa rigueur en raison d'arguments concernant tant le fond que la forme. Cette evaluation peut etre prouvee de facon empirique en faisant une approximation des restrictions d'intervalles. KW - Kreuzvalidierung KW - Strukturgleichungsmodell Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87377 ER -