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  • CYP3A4  (1)
  • GPI-Linked Proteins/genetics  (1)
  • 2015-2019  (1)
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  • 1
    Electronic Resource
    Electronic Resource
    Interindividual variability in catalytic activity and immunoreactivity of three major human liver cytochrome P450 isozymes (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 79-85 
    Details
    ISSN: 1432-1041
    Keywords: Key words Drug metabolism; human liver microsomes ; interindividual variability ; CYP2C9 ; CYP2D6 ; CYP3A4 ; immunoreactivity ; catalytic activity ; cytochrome P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Interindividual variations in immunoreactivity and function of three major human drug metabolising P450 monooxygenases has been investigated in liver microsomes from 42 Caucasians (kidney donors or liver biopsies). Methods: Diclofenac 4′-hydroxylation, dextromethorphan O-demethylation and midazolam 1′-hydroxylation, measured by HPLC in incubates, were used as probes to determine CYP2C9, CYP2D6 and CYP3A4 function kinetics, respectively. Immunoquantification of the three isoforms was achieved by Western blotting, using rabbit polyclonal antibodies raised against human CYP2C9 and human CYP3A4, and mouse monoclonal antibody raised against human CYP2D6. Results: Diclofenac 4′-hydroxylation exhibited Michaelis-Menten kinetics with kM= 3.4 μmol ⋅l−1 and Vmax = 45 nmole ⋅mg−1P ⋅h−1. Relative immunoreactivity of CYP2C9 was correlated with Vmax and CLint. Dextromethorphan O-demethylation in EM (extensive metabolisers) liver microsomes also showed Michaelis-Menten kinetics, with kM = 4.4 μmol ⋅l−1 and Vmax = 5.0 nmol ⋅mg−1P ⋅h−1. Relative immunoreactivity of CYP2D6 was correlated with Vmax and CLint. Midazolam 1′-hydroxylation also exhibited Michaelis-Menten kinetics with kM = 3.3 μmol ⋅l−1 and Vmax = 35 nmol ⋅mg−1P ⋅h−1. Relative immunoreactivity of CYP3A4 was correlated with Vmax and CLint. Immunoreactivity and function were correlated for each isozyme, but there was no cross correlation between isozymes. Conclusion: The velocity of metabolite formation (Vmax) by the three major human drug metabolising P450 monooxygenases is correlated with their immunoreactivity in liver microsomes. Interindividual variation was much larger for Vmax than kM. Interindividual variability was more pronounced for CYP2D6, probably due to the presence of several different functional alleles in the population of extensive metabolisers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050164
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    Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-05
    Description: During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Telley, Ludovic -- Govindan, Subashika -- Prados, Julien -- Stevant, Isabelle -- Nef, Serge -- Dermitzakis, Emmanouil -- Dayer, Alexandre -- Jabaudon, Denis -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1443-6. doi: 10.1126/science.aad8361. Epub 2016 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Biomedical Research Foundation Academy of Athens, Greece. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Saudi Arabia. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Department of Psychiatry, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Clinic of Neurology, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. denis.jabaudon@unige.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26940868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cerebral Ventricles/cytology/embryology ; DNA-Binding Proteins/genetics ; Female ; GPI-Linked Proteins/genetics ; Green Fluorescent Proteins/genetics ; Male ; Mice ; Neocortex/cytology/*embryology ; Nerve Tissue Proteins/genetics ; Neural Stem Cells/cytology ; Neurogenesis/*genetics ; Neurons/*cytology ; Neuropeptides/genetics ; SOXB1 Transcription Factors/genetics ; *Transcription, Genetic ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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