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141.
Nocturnal acid breakthrough is defined as the presence of intragastric pH < 4 during the overnight period for at least 60 continuous minutes in patients taking a proton-pump inhibitor (PPI). Nocturnal acid breakthrough occurs in more than 70% of Helicobacter pylori-negative patients on PPI therapy and has clinical consequences in particular in patients with complicated gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal motility abnormalities. The clinical importance of nocturnal acid breakthrough and the benefit of adding histamine-2 receptor antagonists (H2RAs) to PPI therapy have been debated ever since these concepts were introduced. In our experience, the addition of bedtime H2RAs is clinically effective in controlling nocturnal acid breakthrough and GERD symptoms. 相似文献
142.
Immunization induces less protective immunity against infectious diseases in old compared to young subjects. We have studied the effect of age on the in vitro and in vivo function of murine transgenic T cells expressing a receptor for influenza hemagglutinin 110-120 peptide. During aging the transgenic T cells undergo the age-associated shift from naive to memory phenotype but maintain, despite thymic involution, their number as well as their cytokine production and proliferative responses induced by the hemagglutinin 110-120 peptide in vitro . The maintenance of the size and functions of transgenic T cells during the aging may be related to low expression of CTLA-4 molecules known to exhibit a negative regulatory effect subsequent to interaction with costimulatory molecules as well as of stimulation of T cells by unknown cross reactive endogenous factors but not by nominal antigen since innate immunity prevents natural infection with influenza virus of murine species. This suggests that the impaired immunity induced by immunization in old subjects reflects defects in the development and maintenance of T cell memory and not in the expression of effector activity. 相似文献
143.
144.
Mihai Onofriescu Dimitrie Siriopol Luminita Voroneanu Simona Hogas Ionut Nistor Mugurel Apetrii Laura Florea Gabriel Veisa Irina Mititiuc Mehmet Kanbay Radu Sascau Adrian Covic 《PloS one》2015,10(8)
Background and objectives
Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered.Design, setting, participants and measurements
A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort).Results
In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30–3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72–4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12–3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60–4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48–7.02 for RFO >17.4%) Cox regression analysis.Conclusions
The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations. 相似文献145.
Radu Huculeci Abel Garcia‐Pino Lieven Buts Tom Lenaerts Nico van Nuland 《Protein science : a publication of the Protein Society》2015,24(12):1964-1978
Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide‐bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. 相似文献
146.
Lucia Rubio Radu Huculeci Lieven Buts Sophie Vanwetswinkel Tom Lenaerts Nico A. J. van Nuland 《Biomolecular NMR assignments》2014,8(2):297-301
Src homology 2 (SH2) domains have an important role in the regulation of protein activity and intracellular signaling processes. They are geared to bind to specific phosphotyrosine (pY) motifs, with a substrate sequence specificity depending on the three amino acids immediately C-terminal to the pY. Here we report for the first time the 1H, 15N and 13C backbone and side-chain chemical shift assignments for the C-terminal SH2 domain of the human protein tyrosine phosphatase PTPN11, both in its free and bound forms, where the ligand in the latter corresponds to a specific sequence of the human erythropoietin receptor. 相似文献
147.
Aurelian Gulea Donald Poirier Jenny Roy Vitalie Stavila Ion Bulimestru Victor Tapcov 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):806-818
The present paper describes the synthesis, characterization and in vitro biological evaluation screening of different classes (ammoniacates, dioximates, carboxylates, semi- and thiosemicarbazidates) of Co(II), Co(III), Cu(II), Ni(II), Mn(II), Zn(II) and Fe(III) complexes. Schiff bases were obtained from the reaction of some salicyl aldehydes with, respectively, furoylhydrazine, benzoylhydrazine, semicarbazide, thiosemicarbazide and S-methylthiosemicarbazide to give tridentate ligands containing ONO, ONS or ONN as donor atoms. The synthetic metal complexes are of various geometrical and electronic structures, thermodynamic and thermal stabilities, and magnetic and conductance properties. All complexes, except those of Cu, are octahedral. Some Cu, Co and Mn compounds have a dimeric or a polymeric structure. The composition and structure of complexes were analysed by elemental analysis, IR and 1H NMR and 13C NMR spectroscopies, and magnetochemical, thermoanalytical and molar conductance measurements. All ligands and metal complexes were tested as inhibitors of human leukemia (HL-60) cells growth, and the most potent, the Cu(II) complexes, have been also tested for their in vitro antibacterial and antifungal activities. Structure-activity relationships were carried out. 相似文献
148.
David Shum Constantin Radu Earl Kim Muriel Cajuste Yufang Shao Venkatraman E. Seshan 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):931-945
In response to the need for inexpensive high throughput assays for anti-cancer drug screening, a 1536-well microtiter plate based assay utilizing the Alamar Blue fluorescent dye as a measure of cellular growth was validated in 10 μL assay volume. Its robustness was assessed in a screen against a library of 2000 known bioactives; with an overall Z′ value of 0.89 for assay robustness, several known cytotoxic agents were identified including and not limited to anthracyclines, cardiac glycosides, gamboges, and quinones. To further test the sensitivity of the assay, IC50 determinations were performed in both 384-well and 1536-well formats and the obtained results show a very good correlation between the two density formats. These findings demonstrate that this newly developed assay is simple to set up, robust, highly sensitive and inexpensive. It could potentially provide a rapid way to screen established and primary tumor cell lines against large chemical libraries. 相似文献
149.
Lee HY Chai LC Pui CF Wong WC Mustafa S Cheah YK Mat Issa Z Nishibuchi M Radu S 《Journal of microbiology and biotechnology》2011,21(9):954-959
There have been a number of studies conducted in order to compare the efficiencies of recovery rates, utilizing different protocols, for the isolation of L. monocytogenes. However, the severity of multiple cell injury has not been included in these studies. In the current study, L. monocytogenes ATCC 19112 was injured by exposure to extreme temperatures (60°C and -20°C) for a one-step injury, and for a two-step injury the cells were transferred directly from a heat treatment to frozen state to induce a severe cell injury (up to 100% injury). The injured cells were then subjected to the US Food and Drug Administration (FDA), the ISO-11290, and the modified United States Department of Agriculture (mUSDA) protocols, and plated on TSAyeast (0.6% yeast), PALCAM agar, and CHROMAgar Listeria for 24 h or 48 h. The evaluation of the total recovery of injured cells was also calculated based on the costs involved in the preparation of media for each protocol. Results indicate that the mUSDA method is best able to aid the recovery of heat-injured, freeze-injured, and heat-freeze-injured cells and was shown to be the most cost effective for heat-freeze-injured cells. 相似文献
150.
Olusesan AT Azura LK Abubakar F Mohamed AK Radu S Manap MY Saari N 《Journal of molecular microbiology and biotechnology》2011,20(2):105-115
Bacillus strain NS 8, a lipase-producing bacterium isolated from a Malaysian hot spring, is able to tolerate a broad range of temperature and pH, which makes it beneficial for this study. It generated PCR products with molecular weight of 1,532 bp, and the 16S rRNA sequence analysis identified it as Bacillus subtilis with accession number AB110598. It showed a 71% similarity index with B. subtilis using Biolog Microstation System. Its lipase production was optimized using a shake flask system by changing the physical (agitation speed, pH and temperature) and nutritional (nitrogen, carbon and minerals) factors. The most suitable combination of the basal medium for lipase production was 2.5% olive oil (carbon), 1.5% peptone (nitrogen), 0.1% MgSO(4) (mineral) at an optimum temperature of 50°C, pH 7.5 and 150 rpm agitation, giving an enzyme yield of 4.23 U/ml. Statistical optimization using response surface methodology was carried out. An optimum lipase production of 5.67 U/ml was achieved when olive oil concentration of 3%, peptone 2%, MgSO(4)·7H(2)O 0.2% and an agitation rate of 200 rpm were combined. Lipase production was further carried out inside a 2-liter bioreactor, which yielded an enzyme activity of 14.5 U/ml after 15 h of incubation. 相似文献