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  • Isotopes  (2)
  • Myeloid Neoplasia  (2)
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  • 1
    ISSN: 1433-8580
    Keywords: Dilution curves ; Flow measurement ; Isotopes ; Animal experiments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurden Tierexperimente durchgeführt, um zu beweisen, daß es möglich ist, die Durchblutung eines peripheren Organs mit der Isotopenverdünnungsmethode nach i.v. Injektion zu messen. Es konnte gezeigt werden, daß die mathematische Beschreibung der Verdünnungsvorgänge in 3 Mischkammern in Reihe, die in einer vorhergehenden Arbeit dargestellt wurde, auch für den tierischen Organismus gilt, wo rechtes und linkes Herz sowie peripheres Capillargebiet als Mischkammern wirken. Die für den Verdünnungsvorgang im peripheren Organ errechnete Zeitkonstante ist umgekehrt proportional der Durchblutung, die mit einem elektromagnetischen Flowmeter gemessen wurde.
    Notes: Summary Animal experiments were carried out to prove that it is possible to estimate the blood flow through peripheral organs with the isotope dilution technique after intravenous injection. It could be shown that the mathematical treatment of the dilution events in three mixing chambers in a row, presented in a foregoing paper, is valid also for the animal organism where the mixing chambers are right heart, left heart and peripheral capillary system. The time constant calculated for the dilution event within the peripheral organ is inversely proportional to the blood flow through this organ measured with an electromagnetic flowmeter.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-8580
    Keywords: Dilution curves ; Isotopes ; Flow measurement ; Volume determination ; Model experiments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Wir entwickelten auf Grund des mathematischen Modells von Newman et al. Berechnungsmethoden, um Flow oder Volumen unbekannter Mischkammern zu bestimmen. Um die Geometrieprobleme, die bei der Isotopenmessung auftreten, zu umgehen, schlagen wir Berechnungsmethoden vor, die unabhängig sind von der absoluten Größe der gemessenen Intensität. Diese Berechnungsmethoden, die durch ein Computerprogramm realisiert werden können, wurden in einem Kreislaufmodell untersucht. Das Modell bestand aus einer Kolbenpumpe als erster Mischkammer und zwei weiteren Mischkammern. Es konnte gezeigt werden, daß die Charakteristika der über diesen Kammern gemessenen Isotopenverdünnungskurven den Charakteristika errechneter Kurven entsprechen, daß Flow und Volumenberechnungen, die auf diesen Kurven basieren, nicht nur für kontinuierlichen, sondern auch für pulsatilen Flow gelten und daß diese Art der Flowmessung auch möglich ist, wenn ein Teil des Flows zwischen den Kammern abgezweigt wird.
    Notes: Summary Based on the mathematical model of Newmanet al. we developed calculation methods for the determination of flow or volume of unknown mixing chambers. To avoid the geometrical problems arising by monitoring isotopes we propose calculation methods independent from the absolute value of the measured intensity. These calculation methods which can be realized by a computer program are examined in a circulation model. The model consisted of a piston pump as first mixing chamber and two other mixing chambers. It could be demonstrated that the characteristics of the isotope dilution curves obtained over these chambers correspond to the characteristics of calculated curves and that the flow and volume calculations based on these curves are not only valid for the continuous flow but also for the pulsatile flow and that this type of flow measurement is also possible no matter how much of the flow is branched off between the chambers.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2014-06-20
    Description: Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34 + /CD38 CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4 + SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26 + LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26 + CML LSC engrafted NOD-SCID-IL-2R –/– (NSG) mice with BCR/ABL1 + cells, whereas CD26 SC from the same patients produced multilineage BCR/ABL1 – engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1 + cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy.
    Keywords: Myeloid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2012-05-04
    Description: Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) are advanced hematopoietic neoplasms with poor prognosis. In these patients, neoplastic mast cells (MCs) are resistant against various drugs. We examined the effects of 2 demethylating agents, 5-azacytidine and decitabine on growth and survival of neoplastic MCs and the MC line HMC-1. Two HMC-1 subclones were used, HMC-1.1 lacking KIT D816V and HMC-1.2 exhibiting KIT D816V. Both agents induced apoptosis in HMC-1.1 and HMC-1.2 cells. Decitabine, but not 5-azacytidine, also produced a G 2 /M cell-cycle arrest in HMC-1 cells. Drug-induced apoptosis was accompanied by cleavage of caspase-8 and caspase-3 as well as FAS- demethylation and FAS–re-expression in neoplastic MCs. Furthermore, both demethylating agents were found to synergize with the FAS-ligand in inducing apoptosis in neoplastic MCs. Correspondingly, siRNA against FAS was found to block drug-induced expression of FAS and drug-induced apoptosis in HMC-1 cells. Neither 5-azacytidine nor decitabine induced substantial apoptosis or growth arrest in normal MCs or normal bone marrow cells. Together, 5-azacytidine and decitabine exert growth-inhibitory and proapoptotic effects in neoplastic MCs. These effects are mediated through "FAS–re-expression" and are augmented by the FAS-ligand. Whether epigenetic drugs produce antineoplastic effects in vivo in patients with ASM and MCL remains to be determined.
    Keywords: Myeloid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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