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  • Electronic Resource  (2)
  • 32.90  (1)
  • Key words Acute lymphoblastic leukemia  (1)
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  • Electronic Resource  (2)
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  • 1
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The European physical journal 1 (1986), S. 151-156 
    ISSN: 1434-6079
    Keywords: 32.90 ; 32.30 ; 35.10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract By optical interference and VUV spectroscopy the doublet system of SbI 5p 26s was investigated, so that now the hyperfinestructure of all 8 levels of 5p 26s (A- andB-splitting constants) are known. From the analysis we receive a spin-orbit parameter ζ5p =3,538(57) cm−1 and from the hyperfine-analysis single electron splitting constantsa 5p 01 =52.4(4.6),a 5p 10 =−1.6(7.3),a 5p 12 =72.3(2.3),a 6s 10 =91.7(4.1),b 5p 02 =−49.6(1.1) andb 5p 11 =30.4(3.2) (all values in mK). For all calculations in the fs- and hfs-analysis the 5p 26s 2 D 3/2 has to be excluded (see discussion). With the figures given above the quadrupole moment121 Q(5p 26s)=−0.44(3) barn was obtained. It is in good agreement with the121 Q(5p 3). For the core-polarization by the 5p electron in the innerfieldns-shells (n=1, 2, 3, 4, 5) and the unpaired 6s electron a field of +500(300) kG was obtained.
    Type of Medium: Electronic Resource
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