TY - BOOK A1 - Höhne, Tim T1 - Einflüsse von Make or Buy-Entscheidungen auf die Termintreue Y1 - 2010 SN - 978-3-940565-64-8 N1 - Ergebnisse aus der Produktionstechnik ; 2010,8 / Zugl.: Aachen, Techn. Hochsch., Diss., 2010 PB - Apprimus Verl. CY - Aachen ER - TY - JOUR A1 - Ross, Jillian A1 - Plummer, Simon M. A1 - Rode, Anja A1 - Scheer, Nico A1 - Bower, Conrad C. A1 - Vogel, Ortwin A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Elcombe, Clifford R. T1 - Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo JF - Toxicological Sciences N2 - Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained. Y1 - 2010 U6 - https://doi.org/10.1093/toxsci/kfq118 SN - 1096-0929 VL - 116 IS - 2 SP - 452 EP - 466 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Wolf, C. Roland T1 - In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice JF - Drug Metabolism and Disposition N2 - Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound. Y1 - 2010 U6 - https://doi.org/10.1124/dmd.109.031872 SN - 1521-009X VL - 38 IS - 7 SP - 1046 EP - 1053 PB - ASPET CY - Bethesda ER - TY - BOOK A1 - Matcha, Heike T1 - Therme mit Gästehaus : Masterentwurf WS 2009/2010 Y1 - 2010 SN - 978-3-88536-115-2 PB - Technische Universität Darmstadt CY - Darmstadt ER - TY - BOOK A1 - Matcha, Heike T1 - Konzerthaus in Stralsund : Masterentwurf SS 2009 Y1 - 2010 SN - 978-3-88536-114-5 PB - Technische Universität Darmstadt CY - Darmstadt ER - TY - BOOK A1 - Matcha, Heike T1 - Lamborghini an der Spree : Masterentwurf WS 2008/2009 Y1 - 2010 SN - 978-3-88536-113-8 PB - Technische Universität Darmstadt CY - Darmstadt ER - TY - BOOK A1 - Matcha, Heike A1 - Quasten, Gero A1 - Rabighomi, Hossein T1 - Qualitätssteigerung im verdichteten Wohnungsbau über Erzeugung größerer Vielfalt und Flexibilität durch individualisierte Massenfertigung am Beispiel gestapelter Reihenhäuser Y1 - 2010 SN - 978-3-8167-8216-2 PB - Fraunhofer IRB Verlag CY - Stuttgart ER - TY - CHAP A1 - Matcha, Heike ED - Hauschild, Moritz ED - Karzel, Rüdiger T1 - Regelbasierte Planung - Parametrik T2 - Digitale Prozesse: Planung, Gestaltung, Fertigung Y1 - 2010 SN - 978-3-920034-35-5 N1 - gedruckt in der Bereichsbibliothek Bayernallee unter der Signatur: 11 WTP 101 ; auch als Online-Ausgabe verfügbar SP - 24 EP - 24 PB - Ed. Detail CY - München ER - TY - CHAP A1 - Matcha, Heike ED - Hauschild, Moritz ED - Karzel, Rüdiger T1 - Regelbasierte Planung - Parametrik T2 - Digitale Prozesse : Planung, Gestaltung, Fertigung Y1 - 2010 SN - 978-3-95553-022-8 U6 - https://doi.org/10.11129/detail.9783955530228 N1 - auch gedruckt in der Bereichsbibliothek Bayernallee unter der Signatur 11 WTP 101 SP - 24 EP - 24 PB - Detail CY - München ER - TY - BOOK A1 - Matcha, Heike T1 - Expo 15 : Experimental Parametric Object ; Realisierung des Messestandes "Digital Origami" für den Fachbereich Architektur der Technischen Universität Darmstadt Y1 - 2010 PB - Technische Universität Darmstadt CY - Darmstadt ER -