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991.
KY Hostetler GD Kini JR Beadle KA Aldern MF Gardner R Border R Kumar L Barshak CN Sridhar CJ Wheeler DD Richman 《Canadian Metallurgical Quarterly》1996,31(1-2):59-67
Phosphonoformate (PFA) effectively inhibits viral polymerases but is relatively ineffective in virus-infected cells in tissue culture. A lipid prodrug of phosphonoformate was synthesized by coupling the phosphonate residue of phosphonoformate to the sn-3 hydroxyl of 1-O-octadecyl-sn-glycerol. This prodrug, 1-O-octadecyl-sn-glycero-3-phosphonoformate (ODG-PFA), was 93-fold more active than phosphonoformate in cells infected with the AD169 strain of cytomegalovirus (CMV), and 111-147-fold more active in cells infected with three human clinical isolates of CMV. The compound was also 44-fold more active in human immunodeficiency virus-1 (HIV-1) infected cells and 43-fold more active in cells infected with herpes simplex virus (HSV). Studies of the mechanisms of increased antiviral activity indicate that 1-O-octadecyl-sn-glycero-3-[14C]phosphonoformate is taken up more extensively than the free drug by the host MRC-5 human lung fibroblasts. Intracellular enzymes convert 1-O-octadecyl-sn-glycero-3-phosphonoformate to phosphonoformate. This conversion does not occur in the tissue culture medium containing fetal bovine serum (FBS) or in MRC-5-conditioned medium. In view of its greatly increased in vitro potency and selectivity, 1-O-octadecyl-sn-glycero-3-phosphonoformate may be useful in treating viral diseases. 相似文献
992.
We describe here that parasites of the genus Leishmania contain a cytolytic activity which acts optimally at pH 5.0 to 5.5 and at 37 degrees C in vitro. or the four species examined, Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) major presented considerable hemolytic activity, whereas Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis showed little and no hemolytic activity, respectively. The cytolytic factor of L. amazonensis promastigotes was characterized as a protein with no protease-, phospholipase-, or detergent-like activity, probably localized inside membranous vesicles. The use of osmotic protectants revealed the colloid-osmotic nature of hemolysis, which is indicative of pore formation in the membranes of target cells. This putative pore-forming protein also damaged nucleated cells, including macrophages, causing an increase in their membrane permeability with leakage of cytoplasmic proteins. Both promastigotes and amastigotes express this lytic activity, suggesting that the cytolysin may have a function in both stages of this parasite. The pH and temperature required for optimal activity indicate that it might be more effective within the mammalian host, particularly inside the macrophage parasitophorous vacuole. In promastigotes of L. amazonensis, the expression of lytic activity seems to be regulated during their growth in vitro, being maximal at the early stationary phase. 相似文献
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995.
MF Schuler LS Jefferson J Gorodecki R Glaser J Dietz A Lipton 《Canadian Metallurgical Quarterly》1977,37(6):1662-1665
Perfused rat liver releases growth-promoting activity for viral, spontaneous, and chemically transformed cells. After 5 days of incubation with perfusate, cell lines 3T12-NY (a spontaneous fibroblast transformant), NQ-T1 (a chemically transformed fibroblast line), W-8 (a chemically transformed epithelial rat liver cell line increase in cell growth above controls. Their respective normal counterparts: 3T3 Cl 42, A31-714, K-16, and HEF are not so stimulated. Within another set, the virally transformed mouse fibroblast cell line, SV3T3, exhibits a 27-fold increase in growth; however, 3T3 (mouse, fibroblasts), Py3T3 (polyomatransformed 3T3 cells), SV-Fl2-101 (a flat revertant line), and SV-Py-3T3 (a doubly transformed line) are nonresponsive. Perfused rat liver also release survival activity for SV-3T3 cells. The growth-stimulating activity in liver perfusate is selective for transformed cells. It is suggested that the liver may play a role in suporting neoplasia in vivo. 相似文献
996.
Several actual cases were presented to show the problems encountered with flight deck vision in the middle-age presbyopic pilot both in the simulator and in flight. We have gained useful knowledge in the proper flight-deck needs and optical corrections for these pilots, which should be passed on to aviation examiners, eye specialists, and pilots themselves. This would relieve a great deal of unnecessary lost time and anxiety which results when the pilot has a correction unsuited for the cockpit and encounters extreme difficulty in simulator work and in actual flight conditions which he does not understand and which can become very frustrating and a source of anxiety because his career is at stake. This anxiety may lead to other functional ocular problems, is unnecessary, and can be prevented. 相似文献
997.
N. Santoro 《Calcolo》1976,13(2):123-129
Two operations on permutations are defined and some of their properties are illustrated.
A particular graph is defined as representation of the permutation set under such operations; this graph consists of strongly
connected components only, having at most eight vertices. 相似文献
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Peroperative tinidazole and placebo treatment were compared with respect to incidence of postoperative infections in a double blind investigation on patients admitted for elective bowel surgery. Patients in the tinidazole group had a significantly reduced postoperative infection rate, compared with the placebo group (7.4% and 46%, respectively). Complications in general were fewer in the tinidazole group and costs for antibiotic treatment decreased. All tinidazole-treated patients had clinically effective blood concentrations of the drug at the time of the operation. In contrast with the placebo-treated subjects, the individuals who developed postoperative wound infections from the tinidazole group had no growth of anaerobic bacteria and no antibody response to Bacteroides sp. The use of tinidazole may therefore be recommended for the prevention of postoperative anaerobic infections in patients undergoing bowel surgery. 相似文献