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121.
P Wlodarski M Wasik MZ Ratajczak C Sevignani G Hoser J Kawiak AM Gewirtz B Calabretta T Skorski 《Canadian Metallurgical Quarterly》1998,91(8):2998-3006
Prompt reconstitution of hematopoiesis after cytoreductive therapy is essential for patient recovery and may have a positive impact on long-term prognosis. We examined the role of the p53 tumor suppressor gene in hematopoietic recovery in vivo after treatment with the cytotoxic drug 5-fluorouracil (5-FU). We used p53 knock-out (p53-/-) and wild-type (p53+/+) mice injected with 5-FU as the experimental model. Analysis of the repopulation ability and clonogenic activity of hematopoietic stem cells (HSCs) and their lineage-committed descendants showed a greater number of HSCs responsible for reconstitution of lethally irradiated recipients in p53-/- bone marrow cells (BMCs) recovering after 5-FU treatment than in the corresponding p53+/+ BMCs. In post-5-FU recovering BMCs, the percentage of HSC-enriched Lin- Sca-1(+) c-Kit+ cells was about threefold higher in p53-/- than in p53+/+ cells. Although the percentage of the most primitive HSCs (Lin- Sca-1(+) c-Kit+ CD34(low/-)) did not depend on p53, the percentage of multipotential HSCs and committed progenitors (Lin- Sca-1(+) c-Kit+ CD34(high/+)) was almost fourfold higher in post-5-FU recovering p53-/- BMCs than in their p53+/+ counterparts. The pool of HSCs from 5-FU-treated p53-/- BMCs was exhausted more slowly than that from the p53+/+ population as shown in vivo using pre-spleen colony-forming unit (CFU-S) assay and in vitro using long-term culture-initiating cells (LTC-ICs) and methylcellulose replating assays. Clonogenic activity of various lineage-specific descendants was significantly higher in post-5-FU regenerating p53-/- BMCs than in p53+/+ BMCs, probably because of their increased sensitivity to growth factors. Despite all these changes and the dramatic difference in sensitivity of p53-/- and p53+/+ BMCs to 5-FU-induced apoptosis, lineage commitment and differentiation of hematopoietic progenitors appeared to be independent of p53 status. These studies suggest that suppression of p53 function facilitates hematopoietic reconstitution after cytoreductive therapy by: (1) delaying the exhaustion of the most primitive HSC pool, (2) stimulating the production of multipotential HSCs, (3) increasing the sensitivity of hematopoietic cells to growth factors, and (4) decreasing the sensitivity to apoptosis. 相似文献
122.
Oligonucleotide N3'-->P5' phosphoramidates (3'-phosphoramidates) are DNA analogs that are presently under investigation as potential therapeutic agents. These compounds may also hold promise as a diagnostic tool. Here, we describe a rapid method for the analysis of single-stranded RNA fragments utilizing 3'-phosphoramidate oligonucleotides as probes in conjunction with capillary gel electrophoresis (CGE). 3'-Phosphoramidate 9-mers were mixed with complimentary RNA, and CGE was used to monitor duplex formation. Complimentary strands of RNA and 3'-phosphoramidate formed duplexes that gave unique relative mobilities based on an internal standard. The ability of CGE to discriminate between perfect duplexes and duplexes that contain a base mismatch was also investigated. However, the primary focus of this work was to determine CGE's ability to detect the presence of the 3'-phosphoramidates/RNA duplex under routine electrophoretic running conditions. Polyacrylamide gel electrophoresis analysis was utilized to verify duplex formation. 相似文献
123.
As with other forms of stress, surgery is a time of fluctuating haemodynamics, physiological shifts, intense metabolic changes, and protein catabolism and anabolism. At times, these changes can occur within hours. There is a reasonable body of literature concerning the adverse effects of surgery on gastric emptying, but not on the effects of surgery on the distribution, metabolism and excretion of drugs. Gastric emptying is diminished or absent following major procedures, which prevent the delivery of orally administered drugs to their major site of absorption, the small bowel. Changes in the paracellular absorption of drugs may occur postoperatively, although transcellular absorption appears to be unimpaired. Distribution is affected by changes in blood volume, alterations in circulation, increases in the extracellular fluid and changes in the circulating plasma protein levels, such as albumin and alpha 1-acid glycoprotein. Little is known about alterations in drug metabolism following surgery. However, it has been shown that systemic hypoxia alters the function of some of the cytochrome P450 (CYP) system and increased levels of cytokines have an effect on the metabolism of at least 1 drug. In addition, the renal elimination of drugs is affected in patients postoperatively, although the effects of biliary clearance in this period are difficult to determine. Despite the lack of research into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery, it is reasonable to recommend vigilance with respect to drug therapy during this period. 相似文献
124.
Rate constants or exchange current densities of electrode surface processes involving adatom arrays are conveniently evaluated by determining that sweep rate, s0 (the reversibility parameter), in a linear potential sweep (LPS) experiment, below which the process just remains kinetically reversible, ie its overpotential is sensibly zero. Transition to irreversibility is characterized by peak potentials, Ep, becoming linear in the log of the sweep rate, s, following a region of independence of s for < s0. A suitable extrapolation procedure enables s0 to be evaluated. However, if s0 is large and/or the resistivity of the solution is appreciable, the IRu drop associated with uncompensated resistance in the measurement system can be comparable with the increase of Ep with log s, when s > s0, rendering evaluation of s0 inaccurate. While compensation or empirical correction for this may be made, it is desirable that the nature of the IRu effect of the LPS I vs E profiles be understood in a more fundamental way. It is the purpose of this communication to provide such a treatment of this effect through evaluation of the actual time-dependent potential that becomes applied to the electrode, and to propose criteria based on the product of s0, Ru and the reaction pseudocapacitance, Cφ for indicating the anticipated extent of the IRu effect in the evaluation of s0. While the transition in the Ep vs log s plot may be due to IRu effects as well as to kinetic irreversibility, when the former are appreciable, it is shown that the corresponding transition in the value of Cφ with increasing log s can usually allow spurious IRu and significant irreversibility effects to be distinguished. 相似文献
125.
Kris J. Kozaczek M.Sc. Clayton O. Ruud Ph.D. Joseph C. Conway Jr. Ph.D. Chin-Jye Yu B.S. Ph.D. 《JOM Journal of the Minerals, Metals and Materials Society》1990,42(5):35-38
An advanced x-ray diffraction technique allows the development of texture components to be monitored and provides supplementary information about the cold work and residual stresses in cold-rolled copper sheet. The new technique confirms the results of an ultrasonic test, except for the ultrasonic test’s sensitivity to grain size. The new x-ray diffraction technique could be adapted to provide in-process, nondestructive evaluation of thin copper sheet, even for material moving at high speeds. 相似文献
126.
The Rise of Twitter in the Political Campaign: Searching for Intermedia Agenda‐Setting Effects in the Presidential Primary 下载免费PDF全文
Bethany A. Conway Kate Kenski Di Wang 《Journal of Computer-Mediated Communication》2015,20(4):363-380
Questions exist over the extent to which social media content may bypass, follow, or attract the attention of traditional media. This study sheds light on such dynamics by examining intermedia agenda‐setting effects among the Twitter feeds of the 2012 presidential primary candidates, Twitter feeds of the Republican and Democratic parties, and articles published in the nation's top newspapers. Daily issue frequencies within media were analyzed using time series analysis. A symbiotic relationship was found between agendas in Twitter posts and traditional news, with varying levels of intensity and differential time lags by issue. While traditional media follow candidates on certain topics, on others they are able to predict the political agenda on Twitter. 相似文献
127.
Nature takes a variety of approaches regarding risk concentration. Stationary life tends to bend but not break, whereas mobile life tends toward risk concentration with stout border protection. Client and network devices tend to follow the latter model. 相似文献
128.
Indices are a common and useful way to summarize a changing field for both the lay and the specialist reader, and it's time that we had them for information security. 相似文献
129.
Among healthcare workers, shiftwork (mostly if nightwork is also included), ageing and work-related stress may be factors leading to impaired health. Such risk factors may also operate in interaction, resulting in an even increased harm for health. The present study aims at evaluating these relationships in a sample of 1842 hospital workers in Northern Italy. Subjects were mainly women, 33.1% were aged > or = 45 yr, and they were almost evenly distributed between dayworkers and rotating shiftworkers (nights included). Shiftwork was associated with poor sleep, while it was protective against gastrointestinal disorders, poor work ability and job dissatisfaction. Work stress was the risk factor with the highest relevance for poor health. Ageing was associated with lower physical health. Few significant interactions were observed. Shiftwork with nights and high work stress significantly interacted in increasing the risk for poor sleep. The "healthy worker effect" may have played a strong role in study findings. 相似文献
130.
Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism. 相似文献