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CYP3A proteins comprise a significant portion of the hepatic cytochrome P450 (CYP) protein and they metabolize around 50% of drugs currently in use. The dissection of the individual contributions of the four CYP3A genes identified in humans to overall hepatic CYP3A activity has been hampered by sequence and functional similarities. We have investigated the(More)
Proteins encoded by the human CYP3A genes metabolize every second drug currently in use. The activity of CYP3A gene products in the general population is highly variable and may affect the efficacy and safety of drugs metabolized by these enzymes. The mechanisms underlying this variability are poorly understood, but they include gene induction, protein(More)
The elucidation of the individual contributions of the four CYP3A genes to the overall CYP3A activity has been hampered by similarities in their sequence and function. We investigated the expression of CYP3A mRNA species in the liver and in various other tissues using gene-specific TaqMan probes. CYP3A4 transcripts were the most abundant CYP3A mRNA in each(More)
Human CYP3A enzymes play a pivotal role in the metabolism of many drugs, and the variability of their expression among individuals may have a strong impact on the efficacy of drug treatment. However, the individual contributions of the four CYP3A genes to total CYP3A activity remain unclear. To elucidate the role of CYP3A7, we have studied its expression in(More)
This paper demonstrates the first steps of a new integrating methodology to develop and analyse models of biological pathways in a systematic manner using well established Petri net technologies. The whole approach comprises step-wise modelling, animation, model validation as well as qualitative and quantitative analysis for behaviour prediction. In this(More)
MOTIVATION Reconstructing and analyzing the metabolic map of microorganisms is an important challenge in bioinformatics. Pathway analysis of large metabolic networks meets with the problem of combinatorial explosion of pathways. Therefore, appropriate algorithms for an automated decomposition of these networks into smaller subsystems are needed. RESULTS A(More)
Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction(More)
For the comparison and analysis of protein structures, it is of interest to find maximal common substructures in a given set of proteins. This question is also relevant for motif definition and structure classification. In this paper we describe first a new suitable representation of the secondary structure topology of a protein by an undirected labeled(More)
We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1(More)