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Induction of tumors in mice by genomic hypomethylation   总被引:1,自引:0,他引:1  
Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.  相似文献   
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Non‐steroidal anti‐inflammatory drugs may potentiate the opioid induced reduction in volatile anaesthetic requirements ( Gomez de Segura et al. 1998 ). This study determined the reduction in the MAC of isoflurane (ISO) produced by ketoprofen (KETO) in dogs anaesthetized with fentanyl (FENT) and ISO. Six healthy female crossbred dogs, weighing 13.5 ± 1.3 (mean ± SD) kg and aged 3.0 ± 0.9 years were studied. Approval of the study was obtained from the institutional ethics committee. Anaesthesia was induced in all dogs via a facemask with 5% ISO in 5 L minute?1 oxygen. The dogs' trachea were intubated and lungs were ventilated to maintain normocapnia (Pe ′CO2 4.7–6 kPa, 35–45 mm Hg). A heating pad was used to maintain body temperature. The animals were anaesthetized four times at one week intervals with the following anaesthetic and analgesic protocols randomly administered. Study 1, MAC (ISO); Isoflurane MAC. Study 2, MAC (ISO + FENT); dogs anaesthetized with ISO received a loading dose of 30 µg kg?1 FENT IV over 20 minutes followed by a maintenance infusion of 0.2 µg kg?1 minute?1 FENT. Study 3, MAC (ISO + FENT + KETO1); as study 2 plus 1 mg kg?1 KETO. Study 4, MAC (ISO + FENT + KETO2); as study 2 plus 2 mg kg?1 KETO. The MAC was determined in duplicate by applying a standard electrical stimulus (50 V, 50 H2 over 60 seconds via two needles placed SC over the tarsus). The stimulus was applied 15 minutes after every step change in anesthetic concentration. The Wilcoxon test was applied to data to determine significant differences among MAC measurements. Fentanyl significantly decreased MAC (ISO) from 1.27% ± 0.02% to 0.73% ± 0.08%, a reduction of 42% (p < 0.05). Ketoprofen 1 mg kg?1 further decreased the MAC value (although not statistically significantly) with a reduction of 47% from MAC (ISO) (0.67% ± 0.13%) and 8% from MAC (ISO + FENT). When KETO 2 mg kg?1 was given, the reduction in MAC was 50% compared to MAC (ISO) (0.63% ± 0.08%; p < 0.05) and 14% compared to MAC (ISO + FENT) p < 0.05. Administration of KETO further reduces MAC (ISO) compared to levels observed with FENT alone. The observed reduction may have clinical advantages.  相似文献   
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A period in darkness or in continuous far-red light can cause the ferns of the species Marsilea vestita Hook. and Grev. to develop as a land form in a medium which normally allows only the water form to develop. Far-red light is more effective than darkness in causing this conversion. The difference in the quality of light reaching plants growing in water or on land may cause this conversion to occur in nature.  相似文献   
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A serological survey to detect antibody titres against Treponema hyodysenteriae was conducted on pigs from 106 herds in Western Australia. Titres indicating a positive result in the tests were determined by examining 400 sera from 4 herds known to be free of swine dysentery, and sera from immunised or experimentally infected pigs. Samples of serum from 40 bacon-weight pigs from each of the 106 herds were then collected at 2 abattoirs. Each serum was tested in enzyme-linked immunosorbent assays (ELISA) against the lipopolysaccharide of T hyodysenteriae of serogroups A, B and E, respectively. To assist in evaluating the test, 19 herds were resampled and retested, and faecal samples from 17 herds were cultured for T hyodysenteriae. Thirty-five of the 106 herds (33%) had serological evidence of infection when only one batch of sera from each herd was tested. The ELISA to detect T hyodysenteriae infection in herds using 40 sera was estimated as having a sensitivity of 77.3% and a specificity of 81.8% based on the owners' opinion of their herds disease status. Prevalence of infection within herds ranged from 2.5% to 47.5%, with a mean of 18%.  相似文献   
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The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half-lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals.  相似文献   
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