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Mutational analysis of the tyrosine phosphatome in colorectal cancers   总被引:1,自引:0,他引:1  
Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.  相似文献   
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There is an increasing incidence of anaphylactic reactions in cats due to the administration of ophthalmic bacitracin, neomycin, polymyxin medications. Most of the reported cases have been fatal. This is the report of a cat that survived the initial episode only to develop renal failure and cardiomyopathy. This lead to euthanasia seven days later. Dr. Kathryn Meyer of the U.S. Pharmacopeia and Dr. Signe Plunkett of the Emergency Animal Clinic in Phoenix are conducting an ongoing study, and they are interested in the reports of any additional cases.  相似文献   
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This study aimed to determine the optimal supply of lactation feed during the transition period to minimize farrowing duration (FD) and maximize colostrum yield (CY) and quality with the overall aim of reducing piglet mortality. A total of 48 sows were stratified for body weight and assigned to six levels of feed supply (1.8, 2.4, 3.1, 3.7, 4.3, and 5.0 kg/d) from day 108 of gestation until 24 h after the onset of farrowing. The number of total born, live-born, and stillborn piglets; birth time and birth weight of each piglet; and frequency of farrowing assistance (FA) was recorded, and blood samples were obtained from newborn piglets at birth. Live-born piglets were further weighed at 12 and 24 h after birth to record weight gain, which in turn was used to estimate intake and yield of colostrum. Colostrum samples were collected at 0, 12, 24, and 36 h after the onset of farrowing. FD was shortest (4.2 h) at intermediate (3.7 kg/d), longest (7.1 to 7.6 h) at low (1.8 and 2.4 kg/d), and intermediate (5.6 to 5.7 h) at high (4.3 and 5.0 kg/d) feed intake (P = 0.004; mean comparison). FA was lowest (0.7% to 0.8%) at intermediate feed intake (3.7 and 4.3 kg/d) and substantially elevated (4.3% to 4.7%) at both lower and higher feed intake (P = 0.01; mean comparison). The cubic contrast revealed 4.1 kg/d as the optimal feed intake to achieve the shortest FD and to minimize FA. Newborn piglets from second-parity sows were less vital than piglets from gilts as evaluated by blood biochemical variables immediately after birth. CY was greatest at 3.1 kg/d (P = 0.04), whereas the cubic contrast revealed 3.0 kg/d as the optimal feed intake to maximize CY. Concentrations of colostral components were affected by the diet, parity, and their interaction except for lactose concentrations. In conclusion, the study demonstrated the importance of proper feed level during the transition period on sow productivity. Moreover, this study estimated 4.1 and 3.0 kg/d as the optimal feed intake during the transition period to improve farrowing characteristic and CY, respectively, and these two feed intake levels supplied daily 38.8 MJ metabolizable energy (ME) and 23.9 g standardized ileal digestible (SID) lysine (3.0 kg/d) or 53.0 MJ ME and 32.7 g SID lysine (4.1 kg/d). The discrepancy of optimal feed intake for optimal farrowing and colostrum performance suggests that it may be advantageous to lower dietary lysine concentration in the diet fed prepartum.  相似文献   
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Leukocytes were isolated from whole blood of wild alligators by differential sedimentation. The leukocytes were disrupted in 5% AcOH and the crude extracts processed by ultrafiltration. The extracts were subjected to solvent exchange (0.1% AcOH) and the fraction that contained macromolecules between 1 and 10 kDa were subjected to further analyses. The acid extracts of the alligator leukocytes exhibited substantial antimycotic activities against six of eight species of Candida yeast tested. In addition, the alligator leukocyte extracts were effective as antimicrobial agents against 10 of 12 bacterial species, and displayed moderate activity against two enveloped viruses (human immunodeficiency virus-1 and herpes simplex virus-1HF). Kinetic analyses revealed that the antimycotic effects of the leukocyte extract occurred rapidly, with 64% fungal growth inhibition within 3 min of exposure. The molecule(s) responsible for the antimicrobial activities were sensitive to proteases, heat-stable, acid soluble, and in the 1–10 kDa range. These data suggest that alligator leukocytes express cationic peptides that are responsible for their antimicrobial properties.  相似文献   
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Cloning of cattle, sheep, and mice by somatic cell nuclear transfer (SCNT) can result in apparently healthy offspring, but the probability of a successful and complete pregnancy is less than 5%. Failures of SCNT pregnancy are associated with placental abnormalities, such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium, and altered basement membrane. The pathogenesis of these changes is poorly understood, but current evidence implicates aberrant reprogramming of donor nuclei by the recipient oocyte cytoplast, resulting in epigenetic modifications of key regulatory genes essential for normal placental development. The purpose of this review is to provide an overview of the anatomic pathology of abnormal placentae of SCNT clones and to summarize current knowledge concerning underlying pathogenetic mechanisms.  相似文献   
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