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  • Articles: DFG German National Licenses  (3)
  • AIDS, Antiviral agent  (1)
  • Dominant negative mutant of raf  (1)
  • Eye uptake  (1)
Source
  • Articles: DFG German National Licenses  (3)
Material
Years
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 291 (1991), S. 139-144 
    ISSN: 0014-5793
    Keywords: AIDS, Antiviral agent ; N-terminal sequence ; Plant protein
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    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
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 20 (1993), S. 1146-1153 
    ISSN: 1619-7089
    Keywords: Single-photon emission tomography ; D-2 dopamine receptor ; Brain imaging ; Basal ganglia ; Eye uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preliminary study of iodine-123 labeled IBF, (S)-5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl] carboxamido-2, 3-dihydrobenzofuran, has demonstrated the potential of using this agent to evaluate the status of the CNS D-2 dopamine receptor in humans. To further characterize this ligand and evaluate single-photon emission tomography (SPET) quantitation, a detailed biodistribution study in monkeys (Macaca fascicularis) with 123I- and 125I-IBF was performed. The dual tracer was simultaneously injected for in vivo imaging, biodistribution, and ex vivo autoradiography in the same monkey. After the injection, SPET data (10 min/frame × 15) were collected with a triple-head gamma camera. Dynamic imaging data indicated that IBF localized in basal ganglia (BG) with a half life of 90-120 min. Other regions, i.e., cerebellum (CB) and cortex (CX), showed very low uptake. At 2.2 h after the injection, the monkey was sacrificed. Organ distribution data indicated that, as expected, there was a significant uptake in basal ganglia (0.029% ID/g), and the BG/CB and BG/CX ratios were 17.8 and 14.2 respectively. Lower ratios were obtained from SPET image analysis (BG/CB=3.5 at 2.5h). The eye uptake was observed with SPET, but was only quantified on autoradiograms with significant uptake (0.017% ID/g). Autoradiography of the eye demonstrated that predominant uptake was localized in the ciliary body and the choroid. The selective retention and high BG/CB ratio of 123I-IBF make it a useful agent for in vivo D-2 dopamine receptor imaging with SPET.
    Type of Medium: Electronic Resource
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