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941.
Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1N8-bis(ethyl)spermidine. 总被引:7,自引:6,他引:1 下载免费PDF全文
Polyamine biosynthesis in intact cells can be exquisitely controlled with exogenous polyamines through the regulation of rate-limiting biosynthetic enzymes, particularly ornithine decarboxylase (ODC). In an attempt to exploit this phenomenon as an antiproliferative strategy, certain polyamine analogues have been identified [Porter, Cavanaugh, Stolowich, Ganis, Kelly & Bergeron (1985) Cancer Res. 45, 2050-2057] which lower ODC activity in intact cells, have no direct inhibitory effects on ODC, are incapable of substituting for spermidine (SPD) in supporting cell growth, and are growth-inhibitory at micromolar concentrations. In the present study, the most effective of these analogues, N1N8-bis(ethyl)SPD (BES), is compared with SPD in its ability to regulate ODC activity in intact L1210 cells and in the mechanism(s) by which this is accomplished. With respect to time and dose-dependence of ODC suppression, both polyamines closely paralleled one another in their response curves, although BES was slightly less effective than SPD. Conditions of minimal treatment leading to near-maximal ODC suppression (70-80%) were determined and found to be 3 microM for 2 h with either SPD or BES. After such treatment, ODC activity was fully recovered within 2-4 h when cells were re-seeded in drug-free media. By assessing BES or [3H]SPD concentrations in treated and recovered cells, it was possible to deduce that an intracellular accumulation of BES or SPD equivalent to less than 6.5% of the combined cellular polyamine pool was sufficient to invoke ODC regulatory mechanisms. Decreases in ODC activity after BES or SPD treatment were closely paralleled by concomitant decreases in ODC protein. Since cellular ODC mRNA was not similarly decreased by either BES or SPD, it was concluded that translational and/or post-translational mechanisms, such as increased degradation of ODC protein or decreased translation of ODC mRNA, were probably responsible for regulation of enzyme activity. Experimental evidence indicated that neither of these mechanisms seemed to be mediated by cyclic AMP or ODC-antizyme induction. On the basis of the consistent similarities between BES and SPD in all parameters studied, it is concluded that the analogue most probably acts by the same mechanisms as SPD in regulating polyamine biosynthesis. 相似文献
942.
Pinealectomy or radical sham pinealectomy were performed on adult golden-mantled ground squirrels,Spermophilus (=Citellus) lateralis, approximately 1 month prior to the date of normal winter emergence. The first hibernatory period and subsequent active season were not different in either of the operated groups from intact animals. However, although the initiation of the second hibernatory period was not affected in the pinealectomized animals, this group failed to show the progressive increase in the length of heterothermic bouts that is characteristic of normal hibernation. Also, terminal arousal occurred approximately 6 weeks earlier in the second year after pinealectomy. Male squirrels showed a corresponding time compression in their annual gonadal cycle, as was assessed by testicular state.These results suggest that the pineal gland of the golden-mantled ground squirrel is involved in the expression of the annual hibernatory cycle. In the absence of the pineal gland the adult of this species is unable to sustain the normal depth and duration of hibernation in the second over-wintering period following pinealectomy.We have carried out additional experiments with young, laboratory-bornS. lateralis and with field-caught, adultS. richardsonii. The results of these studies also are described in this paper.Presented at the Ninth International Congress of Biometeorology, 23 Sept – 1 Oct 1981, Osnabrück and Hohenheim, FRG. 相似文献
943.
Rats were trained to perform a fixed ratio-15 operant for food reinforcement during a 30 minute daily session. Naltrexone, in doses up to 45 mg/kg administered 15 min before the behavioral session, failed to disrupt responding. However, 0.3 and 1.0 mg naltrexone/kg produced a dose related potentiation of the operant behavioral suppression induced by 1.0 mg d-amphetamine/kg injected immediately before the session. The naltrexone/d-amphetamine combination also produced excessive salivation and postural abnormalities not seen when either drug was administered alone. [A subsequent study indicated that the salivation induced by naltrexone in combination with d-amphetamine may require previous exposure to naltrexone and/or d-amphetamine.] Blockade of dopamine receptors with pimozide did not modify the interaction. Functional noradrenergic blockade with a low dose of clonidine significantly reversed the potentiated suppression, of operant behavior, as well as the excessive salivation and abnormal posture. These data suggest that there is an important noradrenergic component to the interaction of naltrexone with d-amphetamine. The impressive interaction of behaviorally inactive doses of naltrexone with a moderate dose of d-amphetamine reported here for rats may have clinical implications for detoxified opiate addicts maintained on naltrexone in antagonist therapy programs. 相似文献
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945.
During a 6-month period, 7252 faeces specimens were examined for Escherichia coli serotype O157:H7. Forty-nine specimens (0.7%) from 19 patients yielded this organism. Escherichia coli O157:H7 was the third most frequently isolated bacterial pathogen, following Campylobacter jejuni and (or) Salmonella sp. Although regional variation between laboratories determined whether Campylobacter jejuni or Salmonella was the primary bacterial pathogen isolated, E. coli O157:H7 was consistently isolated more frequently than either Shigella or Yersinia enterocolitica. 相似文献
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947.
Danielle E. Haulsee Dewayne A. Fox Matthew W. Breece Tonya M. Clauss Matthew J. Oliver 《PloS one》2016,11(2)
We developed a long-term tagging method that can be used to understand species assemblages and social groupings associated with large marine fishes such as the Sand Tiger shark Carcharias taurus. We deployed internally implanted archival VEMCO Mobile Transceivers (VMTs; VEMCO Ltd. Nova Scotia, Canada) in 20 adult Sand Tigers, of which two tags were successfully recovered (10%). The recovered VMTs recorded 29,646 and 44,210 detections of telemetered animals respectively. To our knowledge, this is the first study to demonstrate a method for long-term (~ 1 year) archival acoustic transceiver tag implantation, retention, and recovery in a highly migratory marine fish. Results show low presumed mortality (n = 1, 5%), high VMT retention, and that non-lethal recovery after almost a year at liberty can be achieved for archival acoustic transceivers. This method can be applied to study the social interactions and behavioral ecology of large marine fishes. 相似文献
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