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排序方式: 共有62条查询结果,搜索用时 15 毫秒
31.
Samson Mani Katarzyna Szymańska Cyrille Cuenin David Zaridze Karen Balassiano Sheila CS Lima Elena Matos Alexander Daudt Sergio Koifman Victor Wunsch Filho Ana MB Menezes Maria Paula Curado Gilles Ferro Thomas Vaissière Bakary S Sylla Massimo Tommasino Luis Felipe Ribeiro Pinto Paolo Boffetta Pierre Hainaut Paul Brennan Zdenko Herceg 《Epigenetics》2012,7(3):270-277
Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.Key words: DNA methylation, upper aerodigestive tract, cancer, risk factors, biomarkers 相似文献
32.
Microbialites and global environmental change across the Permian-Triassic boundary: a synthesis 总被引:1,自引:0,他引:1
Kershaw S Crasquin S Li Y Collin PY Forel MB Mu X Baud A Wang Y Xie S Maurer F Guo L 《Geobiology》2012,10(1):25-47
Permian-Triassic boundary microbialites (PTBMs) are thin (0.05-15 m) carbonates formed after the end-Permian mass extinction. They comprise Renalcis-group calcimicrobes, microbially mediated micrite, presumed inorganic micrite, calcite cement (some may be microbially influenced) and shelly faunas. PTBMs are abundant in low-latitude shallow-marine carbonate shelves in central Tethyan continents but are rare in higher latitudes, likely inhibited by clastic supply on Pangaea margins. PTBMs occupied broadly similar environments to Late Permian reefs in Tethys, but extended into deeper waters. Late Permian reefs are also rich in microbes (and cements), so post-extinction seawater carbonate saturation was likely similar to the Late Permian. However, PTBMs lack widespread abundant inorganic carbonate cement fans, so a previous interpretation that anoxic bicarbonate-rich water upwelled to rapidly increase carbonate saturation of shallow seawater, post-extinction, is problematic. Preliminary pyrite framboid evidence shows anoxia in PTBM facies, but interbedded shelly faunas indicate oxygenated water, perhaps there was short-term pulsing of normally saturated anoxic water from the oxygen-minimum zone to surface waters. In Tethys, PTBMs show geographic variations: (i) in south China, PTBMs are mostly thrombolites in open shelf settings, largely recrystallised, with remnant structure of Renalcis-group calcimicrobes; (ii) in south Turkey, in shallow waters, stromatolites and thrombolites, lacking calcimicrobes, are interbedded, likely depth-controlled; and (iii) in the Middle East, especially Iran, stromatolites and thrombolites (calcimicrobes uncommon) occur in different sites on open shelves, where controls are unclear. Thus, PTBMs were under more complex control than previously portrayed, with local facies control playing a significant role in their structure and composition. 相似文献
33.
J. O'Grady MB ChB MRCP. S. Warrington MB BChir MA MRCP. M.J. Moti S. Bunting BSc. R. Flower BSc PhD. A.S.E. Fowle MD MRCP. E.A. Higgs BSc MSc. S. Moncada MD PhD. 《Prostaglandins & other lipid mediators》1980,19(2):319-332
Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects.The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting.Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio. 相似文献
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36.
JS Agerholm O Andersen MB Almskou C Bendixen J Arnbjerg GP Aamand US Nielsen F Panitz AH Petersen 《Acta veterinaria Scandinavica》2004,45(3):133
To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were
performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and
insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after
insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if
the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected
calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses.
The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders. 相似文献
37.
Stéphanie Dizier Jean-Marie Forel Louis Ayzac Jean-Christophe Richard Sami Hraiech Samuel Lehingue Anderson Loundou Antoine Roch Claude Guerin Laurent Papazian ACURASYS study investigators PROSEVA Study Group 《PloS one》2015,10(12)
Introduction
Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.Methods
The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.Results
The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.Conclusion
Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate. 相似文献38.
Elevated ammonium concentrations in the medium of cultivated cells have
been shown to increase the intracellular levels of uridine-5'-diphospho-
N-acetylglucosamine (UDP-GlcNAc) and uridine-5'-diphospho-N-
acetylgalactosamine (UDP-GalNAc; Ryll et al., 1994). These sugar
nucleotides are substrates for glycosyltransferases in the glycosylation
pathway. In our experiments, recombinant Chinese hamster ovary cells
producing an immunoadhesin glycoprotein (GP1-IgG) have been cultivated
under controlled cell culture conditions in the presence of different
ammonium concentrations.15N-Labeled ammonium chloride (15NH4Cl) was added
exogenously to the cell culture media to determine if ammonium was
incorporated into UDP-GlcNAc and cytidine-5'-
monophospho-N-acetylneuraminic acid (CMP-NANA) pools, and subsequently
incorporated into GP1-IgG as N-linked glycans. The intracellular pools of
UDP-activated hexosamines (UDP-GNAc) were followed during the time course
of the experiment. To assess the extent of15NH4+incorporation into the
glycans of GP1-IgG, the glycoprotein was first purified to homogeneity by
protein A chromatography. Enzymatically released N- glycans were then
analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry. N-Glycans synthesized in the presence of15NH4Cl revealed an
N-glycan-dependent increase in mass-to-charge of 2.5-4.8 Da. These results
indicate that 60-70% of the total nitrogen containing monosaccharides had
incorporated15N. Presumably,15NH4+was incorporated into GlcNAc and N-
acetylneuraminic acid as proposed earlier (Ryll et al., 1994). This might
be a universal and previously not described reaction in mammalian cells
when exposed to nonphysiological but in cell culture commonly found
concentrations of ammonium. The data presented here are of significance for
glycoprotein production in mammalian cell culture, since it has been shown
previously that elevated levels of UDP- activated hexosamines affect
N-glycan characteristics such as branching and degree of amino sugar
incorporation. In addition, our results demonstrate that isotope labeling
in combination with MALDI-TOF-MS can be used as an alternate tool to
radioactive labeling of sugar substrates in metabolic studies.
相似文献
39.
This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system. 相似文献
40.