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171.
TS Dermody ML Nibert JD Wetzel X Tong BN Fields 《Canadian Metallurgical Quarterly》1993,67(4):2055-2063
Previous studies demonstrated that both cellular and viral mutants are selected during maintenance of persistent infections established in murine L cells with high-passage stocks of mammalian reoviruses. In particular, when one culture was cured of persistent infection, the resulting cells were found to support the growth of viruses isolated from persistently infected cultures (termed PI viruses here) better than that of wild-type (wt) viruses (R. Ahmed, W. M. Canning, R. S. Kauffman, A. H. Sharpe, J. V. Hallum, and B. N. Fields, Cell 25:325-332, 1981). To address the nature of cellular and viral mutations selected during maintenance of persistent reovirus infections, we established independent, persistently infected cultures with L cells and high-passage stocks of wt reovirus. These cultures served as sources of new PI viruses and cured cells for study. We found that although wt viruses grew poorly in cured cells when infection was initiated with intact virions, they grew well in cured cells when infection was initiated with infectious subvirion particles generated from virions by in vitro treatment with chymotrypsin. This finding indicates that the block to growth of wt viruses in cured cells involves an early step that is unique to infection by virions, such as proteolytic processing in an endocytic compartment. We also found that PI viruses grew better than wt viruses in L cells treated with ammonium chloride, a weak base that inhibits the pH decrease in endosomes and lysosomes. Because ammonium chloride blocks an early step in infection by intact virions, probably the proteolytic processing of viral outer capsid proteins by acid-dependent cellular proteases in late endosomes or lysosomes, this finding indicates that PI viruses differ from wt viruses with respect to viral entry into cells. Therefore, these results indicate that both cells and viruses evolve mutations that affect one or more early steps in the viral growth cycle during maintenance of L-cell cultures persistently infected with reoviruses. 相似文献
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Hypothalamic and pituitary insulin-like growth factor II (IGF-II) peptide concentrations are differentially regulated by factors associated with metabolism such as insulin and glucoprivation. However, the effects of other metabolic stressors such as food restriction or exercise on hypothalamic IGF-II concentrations remain largely to be explored. In order to assess whether metabolic stress alters central nervous system IGF-II secretion, peptide analysis was conducted in rats exhibiting activity-based anorexia (ABA) compared to exercised-matched, body weight-matched or ad libitum fed controls. Further, the possibility of serotonergic control of IGF-II secretion was examined by determining IGF-II response to fluoxetine (FLX) injections (15 mg/kg body wt., i.p.). While ABA and body weight loss altered peripheral IGF-II concentrations compared to ad libitum fed or exercised controls, these treatments had no effect on hypothalamic or posterior pituitary IGF-II content. However, FLX administration increased IGF-II concentrations in the ventromedial hypothalamus and decreased IGF-II content in the lateral hypothalamus compared to vehicle injected. Anterior pituitary levels of IGF-II were also decreased by FLX. These data suggest that a serotonergic influence on CNS IGF-II exists and that IGF-II secretion may be altered by factors affecting serotonin metabolism or efficacy. 相似文献
177.
ML Kuo SC Shen CH Yang SE Chuang AL Cheng TS Huang 《Canadian Metallurgical Quarterly》1998,17(17):2225-2234
Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme responsible for DNA strand breaks, has been recently suggested to be crucial for apoptosis induced by a number chemotherapeutic drugs. In this study, we demonstrated that the PARP activity could be evidently elevated with a peak at 6 h when HL-60 cells were treated with a new anticancer drug GL331. Coincident with the peak of PARP activity, an apparent DNA fragmentation and apoptotic morphology were observed in cells treated with GL331. The subsequent apoptotic DNA fragmentation induced by GL331 could be completely blocked by transfecting cells with anti-sense PARP retroviral vector or by treating cells with PARP inhibitor, 3-aminobenzamide (3-AB). This blocking effect thus suggests that activation of PARP was critically involved in GL331-induced apoptosis. The fact that Bcl-2 has been found to antagonize cell death induced by a wide variety of agents, accounts for why we examined whether if Bcl-2 could antagonize GL331 effects. Interestingly, ectopic overexpression of Bcl-2 in either HL-60 or U937 cells caused in resistance towards GL331-elicited DNA fragmentation and cytotoxic effect. Additionally, Bcl-2 also attenuated the poly(ADP-ribosyl)ation of PARP itself as well as Histone H1 at the early period of drug treatment. However, Bcl-2 did not influence the extent of DNA strand breaks induced by GL331 in either control or Bcl-2-overexpressing cells. In addition, analysis of basal PARP activity in control and several Bcl-2 overexpressing clones revealed that Bcl-2 down-regulated PARP activity under the condition without DNA damages. Above findings suggest that poly(ADP-ribosyl)ation of nuclear targets is important for apoptosis induced by DNA-reactive anticancer drugs. 相似文献
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TS Lian JA Bellan JS Jahr RH Holton BD Nossaman PJ Kadowitz 《Canadian Metallurgical Quarterly》1996,27(1-2):73-87
Desmopressin is a synthetic analog of vasopressin used to promote hemostasis and reduce postoperative blood loss. Recent studies have shown that desmopressin decreases arterial blood pressure in the anesthetized rat and relaxes isolated segments of aorta and pulmonary artery. Responses to a clinical preparation of desmopressin were investigated in the hindquarters vascular bed of the cat under constant flow conditions so that changes in perfusion pressure directly reflect changes in vascular resistance. Responses to desmopressin and its vehicle, and the effect of receptor antagonists, inhibitors of prostaglandin, and nitric oxide synthesis inhibitors, were investigated. 相似文献
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