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991.
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
992.
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
993.
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
994.
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997.
In this paper we attempt to explain the abnormality of a simelian foetus with reference to our present knowledge of vertebrate development. The various developmental defects seem to have a single common origin: the speeding-up of the progression of cell differentiation in the notochord anlage--which is the organization centre of the embryo--during the regression of the Hensen's node. Cell activity involved in the morphogenetic movements in the chordamesoderm probably stopped before it should have. The elongation of the notochord anlage was not completed, resulting in the defective development of the posterior part of the foetus. A number of pairs of posterior trunk somites were not induced. Consequently (1) the pelvic limb buds, whose posterior parts were missing, fused, bringing in further developmental deviations in the limb skeleton and abdominal muscles; (2) there are no vertebrae between the first sacral vertebra and the misshaped coccyx formed by the tail bud. The derivatives of the posterior endoderm (hindgut, bladder and ureters) were not induced either. The cauda equina is deficient. The absence of functional kidneys and the presence of embryonic urinary tubules in the pelvic cysts which are wrapped up by gut epithelium suggest the induction of the metanephric mesenchyme by ectopic endoderm. The speeding-up of differentiation in the notochord anlage also probably resulted in the excessive extension of its anterior region which is the organizer of brain structures. This explains the overdevelopment of the nose and of the neurocranium, and the low position of the ear. A gene mutation as well as a mechanical stress are the possible causes of the abnormal behaviour of the notochord anlage. 相似文献
998.
999.
Differential Thermolability of Exonuclease and Endonuclease Activities of the recBC Nuclease Isolated from Thermosensitive recB and recC Mutants 总被引:15,自引:10,他引:5 下载免费PDF全文
Sidney R. Kushner 《Journal of bacteriology》1974,120(3):1219-1222
The recBC nuclease (also called exonuclease V) has been partially purified from Escherichia coli K-12 strains carrying the thermosensitive recB270, recC271, and recB270 recC271 mutations. Of the multiple activities associated with the enzyme, only the adenosine 5'-triphosphate-dependent exonucleolytic hydrolysis of duplex deoxyribonucleic acid (DNA) is abnormally thermolabile. The exo- and endonucleolytic degradation of single-stranded DNA is no more thermosensitive than that catalyzed by the wild-type enzyme. These results suggest that the defects in genetic recombination, DNA repair, and the maintenance of cell viability observed in recBC mutants in vivo result primarily from the specific loss of adenosine 5'-triphosphate-dependent exonuclease active on duplex DNA. 相似文献
1000.
In this paper we describe the use of punched feature cards in a general practice for 18 months. Its advantages are the low cost, speed of information retrieval, visible statistics, computer compatibility, accuracy, confidentiality, flexibility, and simplicity of setting up and collection of information. The system encourages the doctor to ask questions about his practice, and could readily be adopted in other practices. 相似文献