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  • 1
    Electronic Resource
    Electronic Resource
    Mechanisms of resistance to methotrexate in childhood acute lymphoblastic leukemia: circumvention of thymidylate synthase inhibition (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 513-519 
    Details
    ISSN: 1432-1335
    Keywords: Key words Acute lymphoblastic leukemia ; Methotrexate polyglutamates ; Thymidylate synthase ; Salvage pathway ; Relapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: In about 25% of patients suffering from acute lymphoblastic leukemia (ALL) treatment failures occur that are most likely due to development of resistance to methotrexate (MTX). Blasts from patients with ALL were evaluated for MTX uptake, formation of long-chain MTX polyglutamates (MTX-Glu5+6), cytotoxicity and thymidylate synthase inhibition by MTX and compared to blasts from patients with acute myelogenous leukemia (AML). Methods: Radioactively labeled MTX-Glu n were analyzed by means of HPLC. Thymidylate synthase activity was measured by a tritium-release assay. Cytotoxicity was determined by trypan blue exclusion. Results: In most ALL blasts (n = 9) large amounts of MTX-Glu5+6 (1.06–7.03 pmol/107cells) and high cytotoxicity (43.5%–92.7%) were found, while in others small amounts of MTX-Glu5+6 (0.0–0.39 pmol/107cells) caused only weak cytotoxicity (6.0%–27.9%) (n = 5, 2 relapsed patients). Resistance to MTX in blasts from AML patients (n = 5) was also caused by reduced synthesis of MTX-Glu5+6 (0.0–0.42 pmol/107cells). In contrast, some ALL blasts (n = 7, 4 relapsed patients) were able to survive MTX treatment despite large amounts of MTX-Glu5+6 (1.5–5.05 pmol/107cells) and extensive thymidylate synthase inhibition. Conclusions: Since the majority of ALL patients were examined at first diagnosis, an inherent mechanism of resistance seems most likely. We propose a mechanism based on the switch of thymidylate synthesis to the salvage pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050310
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  • 2
    Electronic Resource
    Electronic Resource
    Die Zukunft heißt Europa 10. Europäischer Anästhesiekongreß / 45. Deutscher Anästhesiekongreß (1998)
    Springer
    Der Anaesthesist 47 (1998), S. 803-815 
    Details
    ISSN: 1432-055X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die politische Schlagzeile „Die Zukunft heißt Europa” gilt nicht nur für den politischen Bereich, sondern auch für das Fach Anästhesie mit dem Ziel, einen europäischen Standard unter Berücksichtigung nationaler Interessen zu etablieren. Ein wichtiger Aspekt ist die Standardisierung der Ausbildung, die vom European Board of Anesthesiology, Reanimation and Intensive Care , bestehend aus jeweils zwei gewählten Repräsentanten jedes Mitgliedlandes, im Rahmen der Europäischen Union realisiert werden soll. Einen Beitrag zu diesem Ziel könnte der 10. Europäische und 45. Deutsche Anästhesiekongreß geleistet haben, an dem über 6000 Anästhesisten und Intensivmediziner aus knapp 90 Ländern teilgenommen haben. Den Kongreßteilnehmern wurde ein breites Spektrum anästhesiologischer, intensivmedizinischer, schmerztherapeutischer und notfallmedizinischer Beiträge angeboten, die Basiswissen, Ergebnisse experimenteller Studien und aktuelle Themen vorstellten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050629
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  • 3
    Electronic Resource
    Electronic Resource
    Algorithmus 20 Ein leistungsfähiger Algorithmus zur Bestimmung von K-kürzesten Wegen in einem Graphen (1974)
    Springer
    Computing 12 (1974), S. 273-283 
    Details
    ISSN: 1436-5057
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Description / Table of Contents: Abstract A computer programming algorithm is presented which is based on Yen's principle [1] for finding the K loopless paths that have the shortest lengths from one fixed node to another in a network. Several modifications and extensions permitted to construct an extremely efficient algorithm, with regard to the number of necessary memory addresses as well as to the need of operations. The computer time increases linearly with K and is mostly less than the time of Hoffman-Pavley's algorithm [2], moreover, each of the generated paths is loopless. The algorithm published in this paper may be one of the best methods available till now for the solution of the K-shortest paths problem.
    Notes: Zusammenfassung In der vorliegenden Arbeit wird ein neuer Algorithmus zur Bestimmung K-kürzester Wege in einem Graphen vorgestellt. Der Grundgedanke dazu stammt aus einem Verfahren von Jin Y. Yen [1]. Verschiedene Modifikationen und Erweiterungen ermöglichten die Erstellung eines äußerst wirkungsvollen Algorithmus, sowohl hinsichtlich des benötigten Speicherplatzbedarfs, als auch im besonderen hinsichtlich der notwendigen Rechenoperationen. Die Rechenzeiten liegen durchwegs niedriger als etwa die Zeiten des Verfahrens von Hoffman-Pavley [2]. Der hier beschriebene Algorithmus liefert dabei tatsächlich nur schleifenfreie Kantenfolgen; er dürfte damit wohl eine der besten der zur Zeit bekannten Methoden zur Berechnung K-kürzester Wege darstellen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02293111
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  • 4
    Electronic Resource
    Electronic Resource
    Comparative analysis of methotrexate polyglutamates in lymphoblast preparations from bone marrow and blood, and the contribution of residual red blood cells (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 407-411 
    Details
    ISSN: 1432-1335
    Keywords: Key words Acute lymphoblastic leukemia ; Methotrexate polyglutamates ; Lymphoblast preparation ; Red blood cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Blasts isolated from bone marrow aspirates or blood samples of patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were compared for uptake of methotrexate (MTX) and formation of MTX polyglutamates (MTX-Glu n ). Red blood cells (RBC) from the same patient samples were also analyzed. Methods: Blasts were isolated by standard density centrifugation. RBC were prepared from the pellet of the same centrifugation. MTX-Glu n were analyzed by means of HPLC and radiochemical quantification. Results: In lymphoblasts isolated from blood, the distribution patterns of MTX-Glu n were the same as in bone marrow lymphoblasts, but the total amount of MTX-Glu n accumulated in blood lymphoblasts was reduced by 41%–51% when compared to the same number of bone marrow lymphoblasts of the same patient. RBC accumulated MTX but no formation of MTX-Glu n occurred. Conclusions: The determination of MTX and MTX-Glu n in lymphoblasts isolated from blood samples of patients with common ALL provides qualitative information on the capacity of the blasts to form MTX-Glu n since distribution patterns of MTX and MTX-Glu n parallel that of bone marrow lymphoblasts. The amounts of MTX-Glu n accumulated, however, were much lower in blood lymphoblasts. Blood lymphoblasts are therefore not useful for a quantitative analysis of MTX-Glu n . The contribution of RBC to MTX and MTX-Glu n in vitro is only marginal and residual RBC in lymphoblast preparations from bone marrow can therefore be ignored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008489
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Pyrogentestung mit Vollblut Zusammenfassung eines Status-Workshops am Paul-Ehrlich-Institut, Langen, am 22.11.1999 (2000)
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 43 (2000), S. 525-533 
    Details
    ISSN: 1437-1588
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001030070038
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  • 6
    Electronic Resource
    Electronic Resource
    Algorithmus 27 Ein neuer Algorithmus zur Bestimmung vonk-kürzesten Wegen in einem Graphen (1976)
    Springer
    Computing 16 (1976), S. 139-151 
    Details
    ISSN: 1436-5057
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Description / Table of Contents: Abstract The following algorithm for finding thek-shortest loopless paths from one node to another is a development of the algorithm published in [2]. Though memory need is less, the new algorithm is running is bout 20 times as fast on large networks (1000 nodes and more). The computer time increases linearly withk and about quadratic with the number of nodes on the generated paths.
    Notes: Zusammenfassung Der in der vorliegenden Arbeit vorgestellte Algorithmus zur Ermittlung vonk-kürzesten schleifenfreien Kantenfolgen von einem Anfangsknoten zu einem Endknoten stellt eine Weiterentwicklung des in [2] beschriebenen Verfahrens dar. Bei deutlich geringerem Speicherplatzbedarf konnte die Rechengeschwindigkeit stark gesteigert werden (bei Graphen von 1000 Knoten ungefähr um das 20fache). Die Rechenzeit wächst linear mitk und in etwa quadratisch mit der Knotenzahl der erzeugten Wege.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02241985
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