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  • Dominant negative mutant of raf  (1)
  • Mechanical ventilation  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Induction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK-MAP kinase signal transduction pathway (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 441-449 
    Details
    ISSN: 1432-0843
    Keywords: Key words Oncogenic ras-p21 ; Oocyte maturation ; Dominant negative mutant of raf
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf-MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. Methods: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MAP kinase-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. Results: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. Conclusion: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK-MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MAP kinase inhibitors. The results imply that blockade of both MAP kinase and JNK-oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras- induced tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051017
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Spontaneous variability of arterial oxygenation in critically ill mechanically ventilated patients (1999)
    Springer
    Intensive care medicine 25 (1999), S. 37-43 
    Details
    ISSN: 1432-1238
    Keywords: Key words Spontaneous variability ; Mechanical ventilation ; Arterial oxygenation ; Positive end-expiratory pressure ; Inverse ratio ventilation ; Venous admixture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To assess the magnitude of spontaneous variability of arterial oxygenation and oxygen tension-based indices over time in medical intensive care unit (ICU) patients and to study whether high positive end-expiratory pressure (PEEP) or inverse inspiratory-to-expiratory (I:E) ratio ventilation (IRV) results in a greater variability than low PEEP with conventiona l I:E ratio ventilation. Design: Prospective study. Setting: Medical ICU in a tertiary medical center. Participants: 23 patients requiring a pulmonary artery floating catheter for hemodynamic monitoring. Intervention: After being completely sedated, patients were randomized to receive pressure-control ventilation at setting A: high PEEP (15 cmH2O) with conventional I:E ratio (1:2) and setting B: inverse I:E ratio (2:1) with low PEEP (5 cmH2O) alternately, and then at setting C: low PEEP (5 cmH2O) with conventional I:E ratio (1:2). Each ventilation setting lasted 1 h. Measurements and results: The arterial and mixed venous blood samples were measured simultaneously at baseline (time 0), and at 15, 30, 45, and 60 min thereafter. The coefficient of variation (CV) of arterial oxygen tension (PaO2) over time was 5.9 % for setting A, 7.2 % for setting B, and 6.9 % for setting C. ANOVA showed no significant differences in CVs of PaO2 between the three settings. Oxygen tension-based indices, alveolar-arterial oxygen difference (A-aDO2) and PaO2/PAO2 (alveolar oxygen tension), displayed CV s equal to that of PaO2; the CV of A-aDO2/PaO2 was significantly greater than that of PaO2. Conclusions: In critically ill medical ICU patients, despite sedation, the spontaneous variability in PaO2 over time is substantial. A high PEEP or IRV does not contribute to the increased variation in PaO2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050784
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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