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  • Synaptic ribbons  (2)
  • Daunorubicin  (1)
  • Key words Varicella infection  (1)
  • 1
    ISSN: 1432-2307
    Keywords: P-Glycoprotein ; Multidrug resistance ; Vesicle formation ; Daunorubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the human gastric carcinoma cell line EPG85-257P (parent) induction of resistance to daunorubicin (DAU) was achieved by selection with stepwise increased concentrations of the drug. The new vairant was named EPG85-257DAU and was shown to overexpress the mdr1 gene product 170 kDa P-glycoprotein (P-Gp) as demonstrated by immunocytochemistry and mdr1-specific RT-PCR. To investigate the intracellular pathway of DAU the subcellular distribution of this autofluorescent drug was studied in the resistant cells and compared to its chemosensitive counterpart EPG85-257P. When sensitive cells were exposed to DAU the drug rapidly accumulated in the nucleus until cell death. No redistribution of DAU to the cytoplasm was observed. In resistant cells exposed to the drug DAU also accumulated in the nucleus but to a lesser extent than in parent cells. Following exposure, nuclear fluorescence was observed to decrease over a time period of up to 48 h. Six hours after DAU exposure formation of fluorescent vesicle formation started in the perinuclear region and increased continously. After 48 h nuclear fluorescence was no longer detectable and DAU was located exclusively in vesicles. During this period the vesicles moved from the region of origin to the cell periphery. A pulse chase experiment showed, that vesicles may contain DAU derived from the nucleus. Treatment of EPG85-257DAU cells with DAU in conjunction with the chemosensitizer cyclosporin A (CsA) increased nuclear fluorescence without impairing vesicle formation. Disruption of microtubules by nocodazole led to an accumulation of vesicles in the perinuclear region indicating that microtubules are involved in vesicular transport. Treatment of EPG85-257DAU cells with the actin disruptor cytochalasin B led to accumulation of vesicles in the cell periphery indicating that actin may be involved in exocytosis. Uptake and efflux of DAU and rhodamin (RH) were determined in sensitive and resistant cells using a fluorescence activated cell sorter. Uptake of both compounds was distinctly lower in resistant than in sensitive cells. When resistant cells preloaded for 2 h with RH subsequently were incubated in drug free medium the substance was rapidly released indicating transmembrane transport by P-Gp. In contrast, despite expression of P-Gp in resistant cells no considerable release of DAU was observed for up to 2 h under the same experimental protocol. This indicates that in resistant cells intracellular DAU at least in part may be inaccessible for P-Gp and that vesicular drug transport appears to contribute to DAU resistance by removing intracellular DAU via exocytosis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 157 (1998), S. 814-815 
    ISSN: 1432-1076
    Keywords: Key words Varicella infection ; Neurology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Varicella-related neurological complications usually appear after the rash. Pre-eruptive neurological complications of primary varicella zoster virus infections have been rarely described. We report on a 5.5-year-old boy who developed encephalitis 4 days before the onset of a mild vesicular skin rash and 5 days after known exposure. Primary varicella zoster virus infection was confirmed serologically. Cranial magnetic resonance imaging revealed temporary inflammatory oedema in the right cerebellar peduncle. Conclusion Neurological complications of varicella may appear up to 2.5 weeks before the onset of the exanthema. Physicians treating patients with ataxia or encephalitis should inquire about exposure to varicella zoster virus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0878
    Keywords: Pineal gland ; Synaptic ribbons ; N-acetyl-transferase ; Melatonin ; Serotonin ; Protein synthesis ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To elucidate the role of protein synthesis in the nocturnal increase of synaptic ribbons in the rat pineal gland, actinomycin-D, which inhibits transcription, and cycloheximide, an inhibitor of translation, were used. To assure that the drugs were effective and to relate morphological changes to pineal biosynthetic phenomena, the activity of N-acetyltransferase and levels of pineal indoleamine were measured. Results of in-vivo, short-term and long-term treatment with either drug suggest that transcription of proteins related to synaptic ribbon formation occurs during the first half of the light phase, whereas translation takes place during the first few hours of the dark phase. In contrast, proteins involved in enhanced melatonin synthesis are transcribed and translated during the first few hours of the dark phase. In vitro, preincubation with inhibitors of protein synthesis abolished the increase in the numbers of synaptic ribbons after stimulation with dibutyryl-adenosinecyclic-monophosphate, indicating that the results of the in-vivo experiments are due to an interaction of the drugs with the pineal gland itself. The present study shows that, although in the rat pineal enhanced melatonin synthesis and increased numbers of synaptic ribbons occur at the same time, transcription of proteins involved in both rhythms is temporally separated.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1463
    Keywords: Synaptic ribbons ; diestrous rats ; LHRH ; sex steroids ; dexamethasone ; NAT activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pineal glands of regularly cycling Sprague Dawley rats (180–220 g) killed on the diestrous morning (between 0900–1000 h) were incubated in appropriate media for six hours with LHRH (8.5 ΜM), progesterone (3.2 ΜM), estradiol-17 Β (370 nM) or dexamethasone (250 nM). Pineals incubated in hormone-free medium and unincubated glands served as controls. Six rats were used in each group. After incubation the glands were divided into two parts. One part was used to estimate serotonin N-acetyltransferase (NAT) activity. The other part was processed for electron microscopy to quantify synaptic ribbons (SR). The SR numbers were computed to 20,000 Μm2 area of pineal tissue. The number and distribution pattern of SR were identical in incubated as well as in the unincubated controls. In both these groups the SR located close to the cell membrane were more (23 ± 1) than those that lay away from it (9 ± 2). LHRH had no effect on the number of SR located close, to or distant from, the cell membrane. Incubation of pineals with progesterone significantly (p ⩽ 0.05) depressed the number of SR present close to membranes (23 ± 1 in controls vs 11 ± 2 in treated group), total SR (34 ± 3 in controls vs 21 ± 2 in treated group) and synaptic fields (26 ± 2 in controls vs 17 ± 2 in treated group). Likewise, in the estradiol-17 Β group also membrane-associated SR decreased significantly. The effect of progesterone was more severe than estrogen on the SR possibly due to the differences in the doses used. The SR situated distant from the membranes were unaffected in both progesterone and estrogen groups. In pineals incubated with dexamethasone there was a depressive trend in the number of SR but with no statistical significance. The NAT activity was undetectable in control and all experimental groups. The above findings demonstrate that ovarian sex steroids in vitro are capable of specifically depressing the number of SR located close to the cell membrane while those lying distant from it remain unaffected. Whether or not this differential response is also present in vivo remains to be elucidated.
    Type of Medium: Electronic Resource
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