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41.
We show herein that human DNA topoisomerase II beta is functional in yeast. It can complement a yeast temperature-sensitive mutation in topoisomerase II. The effect on human topoisomerase II beta of a number of topoisomerase II inhibitors was analysed in a yeast in vivo system and compared with that of human topoisomerase II alpha and wild-type yeast topoisomerase II. A drug permeable yeast strain (JN394 top2-4) was used to analyse the in vivo effects of known anti-topoisomerase II agents on human topoisomerase II beta transformants. A parallel analysis on human topoisomerase II alpha transformants provides the first in vivo analysis of the responses of yeast bearing the individual isoforms to these drugs. The strain was analysed at 35 degrees C, a non-permissive temperature at which only plasmid-borne topoisomerase II is active. A shuttle vector with either human topoisomerase II beta, human topoisomerase II alpha or yeast topoisomerase II under the control of a GAL1 promoter was used. The key findings were that amsacrine produced comparable levels of cell killing with both alpha and beta, whilst etoposide, doxorubicin and mitoxantrone produced higher degrees of cell killing with alpha than with beta or yeast topoisomerase II. Merbarone had the greatest effect on the yeast strain bearing plasmid-borne yeast topoisomerase II. Suramin, quercetin and genistein showed little cell killing in this system. This yeast in vivo system provides a powerful way to analyse the effects of anti-topoisomerase II agents on transformants bearing the individual human isoforms. This system also provides a means of analysing putative drug-resistance mutations in human topoisomerase II beta or to select for drug-resistance mutations in human topoisomerase II beta. 相似文献
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We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18) and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps brachii was 11% greater for callipyge (P < .001); however, phenotype did not affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp. 3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P < .05). Regardless of callipyge phenotype, muscles were more (P < .05) tender when roasted; however, the effect of method of cookery on tenderness scores was greater for callipyge muscles than for normal muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and callipyge roasts were more tender than normal chops (P < .05). Regardless of cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting. 相似文献
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DM Adams JS Sholl EI Haney TL Russell RK Silver 《Canadian Metallurgical Quarterly》1998,178(4):843-847
A recent review of the relevant literature indicates that different approaches to the exploration of nurses' clinical reasoning are being adopted in North America, Australia and the United Kingdom. These differing approaches, which tend to cluster chronologically and which include decision analysis, information processing and skills acquisition theory and their limitations will be outlined; it will be argued that it is through their conflation that nurses' collective understanding of nurses' clinical reasoning is deepened. The author is attempting to develop an international network of nurse scholars interested in clinical reasoning with the aim of achieving this. The purposes of this network will be to facilitate international collaboration to expedite both the growth of knowledge related to nurses' clinical reasoning and the development of programs of international comparative research related to it. The setting up of this network and progress to date is described. 相似文献
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Gamma-methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-gamma-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 microM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase I trial. 相似文献
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To see if urinary 2-methyl-4-chlorophenoxyacetic acid (MCPA) excretion could be used to estimate MCPA exposure, four healthy males ingested 5 mg MCPA. The MCPA in the urine was extracted and anlyzed by high pressure liquid chromatography. About 50% of the ingested dose was detected in the urine within 48 h. On the fifth day after intake the MCPA concentration in the urine was below the level of detection, 0.2 microgram/ml. The MCPA did not increase those serum enzymes indicating liver cell damage (S-alanine-aminotransferase, S-alkaline-phosphate). Some creatine kinase (CK) and S-aspartate-aminotransferase (ASAT) values were pathological, but, as all CK values were normal in two persons and all ASAT values were normal in three persons, it not likely that MCPA had a toxic effect on muscle cells. MCPA in urine seems to be a useful indicator of MCPA intake in humans. All the urine passed within 48 h of MCPA exposure must be collected. 相似文献
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In the period reviewed, the Royal Victoria Hospital received over 7000 casualties, representing approximately half of the civil disturbance injuries for the province. Primary resuscitation did not differ from that of road traffic accidents, but the surgical management did. Extensive débridement was essential, followed by delayed primary suture some days later. Two hundred and nine penetrating abdominal wounds were reviewed, and the necessity of exploring the abdomen in all such injuries is emphasized. 相似文献