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  • 1
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    Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-13
    Description: Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975362/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975362/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cronin, Shane J F -- Nehme, Nadine T -- Limmer, Stefanie -- Liegeois, Samuel -- Pospisilik, J Andrew -- Schramek, Daniel -- Leibbrandt, Andreas -- Simoes, Ricardo de Matos -- Gruber, Susanne -- Puc, Urszula -- Ebersberger, Ingo -- Zoranovic, Tamara -- Neely, G Gregory -- von Haeseler, Arndt -- Ferrandon, Dominique -- Penninger, Josef M -- P01 AI044220/AI/NIAID NIH HHS/ -- P01 AI044220-10/AI/NIAID NIH HHS/ -- P01 AI44220/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):340-3. doi: 10.1126/science.1173164. Epub 2009 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19520911" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Cell Proliferation ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*genetics/immunology/*microbiology ; Epithelial Cells/cytology/physiology ; *Genome, Insect ; Hemocytes/immunology/metabolism/microbiology ; Homeostasis ; Immunity, Innate/*genetics ; Intestinal Mucosa/cytology/immunology/metabolism/microbiology ; Janus Kinases/genetics/metabolism ; Models, Animal ; *RNA Interference ; STAT Transcription Factors/genetics/metabolism ; Serratia Infections/genetics/*immunology/microbiology ; Serratia marcescens/*immunology/physiology ; Signal Transduction ; Stem Cells/cytology/physiology
    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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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of 6-thiouric acid and 6-mercaptopurine in renal allograft recipients after oral administration of azathioprine (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 265-271 
    Details
    ISSN: 1432-1041
    Keywords: azathioprine ; 6-thiouric acid ; 6-mercaptopurine ; renal transplantation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (6-TU) and 6-mercaptopurine (6-MP), metabolites of AZA, may provide more readily measurable indices of the pharmacologic activity of AZA. In order to evaluate the utility of 6-TU and 6-MP plasma concentrations in monitoring AZA therapy, we studied their pharmacokinetics in 6 renal transplant patients, and their in vitro immunosuppressive potency in a mixed lymphocyte proliferation assay. A peak plasma 6-TU concentration of 710.7 ng/ml was observed at 3.8 h after oral dosing. Good correlation was observed between the elimination t1/2 of 6-TU and serum creatinine, and between AUC over 24 h and serum creatinine. However, we did not observe a second peak in plasma 6-TU concentration that could be attributed to the degradation of active AZA metabolites. 6-MP plasma concentrations in the patients were low (mean peak concentration 36.0 ng/ml) and rapidly disappeared within 8 h. In vitro immunosuppressive activity could not be demonstrated for 6-TU over a concentration range of 1.25 ng/ml to 0.25 mg/ml. We conclude that 6-TU is pharmacologically inert and is primarily eliminated by the kidneys. Our findings currently do not support the use of plasma concentrations of 6-TU or 6-MP to monitor AZA therapy. In order to optimize AZA therapy, analytical techniques that are technically feasible and that can directly quantify the active intracellular thiopurines are being explored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558158
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