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A prospective study was performed to assess the potential value of interleukin (IL)-8, IL-6, and C-reactive protein (CRP) serum levels to predict fever, gram-negative bacteremia and complicated infection in neutropenic patients with cancer. Serum samples were obtained three times a week during 208 neutropenic episodes following cytotoxic chemotherapy. Fever of any cause developed during 104 out of 191 evaluable episodes. Serum levels of neither cytokine nor CRP were predictive of fever within more than 24 h before its onset. Unlike CRP, both IL-6 and IL-8 serum levels were significantly different between microbiologically documented infections and unexplained fevers. The highest values of IL-6 and IL-8 were observed in episodes of gram-negative bacteremia. Using receiver-operating-characteristic curves, the analysis of cytokine levels measured around the onset of fever indicated that IL-8 is potentially useful for predicting gram-negative bacteremia, with a high negative predictive value of > 90% and a moderate positive predictive value of 50% (sensitivity, 70%; specificity, 91%). In patients with persistent fever, predictions of further clinical complications, defined as prolonged fever of more than 7 days' duration, pneumonia, shock and/or death due to infection, were best predicted by IL-6. With an IL-6 cutoff value of 250 pg/ml in samples obtained 8 to 32 h after onset of fever, the positive predictive value was 92%, the negative predictive value 91% (sensitivity, 85%; specificity, 95%). The positive predictive value of IL-6 in samples obtained another 24 h later from patients still febrile remained > 90%, but the negative predictive value dropped to 47%. In any of the analyses, the predictive values of CRP levels were poor and inferior to either cytokine. These findings may have clinical value in identifying subgroups of patients requiring different therapeutic approaches. 相似文献
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We have used proteolysis to examine the environment through which nascent secretory proteins are translocated across the membrane of the endoplasmic reticulum. After solubilization of rough microsomes with detergent, fragments comprised of the approximately 70 carboxyl-terminal amino acids of translocating nascent chains initiated and targeted in vivo were protected from digestion by added proteases. About 40 amino acids of nascent chains were protected from proteolysis by the ribosome; thus, membrane-derived components protect an additional 30 amino acids. Under conditions in which those 30 additional amino acids are protected, only a small set of integral membrane proteins remained associated with the ribosome. These proteins include the Sec61 complex previously identified as the core component of the membrane-bound protein translocation apparatus. These results support the concept of a translocation pore that makes intimate contact with the ribosome and thereby protects nascent chains from proteolytic digestion for an additional, constant length. 相似文献
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Structure-activity studies of human tumour necrosis factors 总被引:3,自引:0,他引:3
Van Ostade Xaveer; Tavernier Jan; Fiers Walter 《Protein engineering, design & selection : PEDS》1994,7(1):5-12
The mechanism by which tumour necrosis factors (TNF and lymphotoxin,also called TNFß and TNFß respectively) exerttheir cytotoxic activity on many malignant cells, remains largelyunknown. Furthermore, the broad array of differentiation (geneinduction) and mitogenic activities towards many primary cellsis still a subject of intensive investigation. TNF is an importantmediator in inflammation, immune responses and infection-relatedphenomena and these activities contribute to the severe toxidtyseen when TNF is used as an anticancer agent. The first stepin the mechanism of action is the specific binding of the ligandto its receptors and dissection of the molecular mechanism involvedin this interaction is the subject of this review. The reasonsfor the interest in this aspect are obvious: first, the developmentof strong antagonistic TNF analogues can be useful in dampeningthe potentially lethal or debilitating effects of an overproductionof the cytokine (as in septic shock or rheumatoid arthritis).Secondly, since two distinct TNF receptors exist, constructionof TNF muteins that distinguish between both types may leadto derivatives of this plekrtropic agent with a more restrictedbiological activity pattern. Ideally, one would like to developa TNF mutant that has retained its cytotoxic action on tumourcells without inducing the deleterious systemic toxteity. Suchan optimized TNF molecule could become a potent anticancer agent 相似文献
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Johnson-Laird P. N.; Byrne Ruth M. J.; Schaeken Walter 《Canadian Metallurgical Quarterly》1994,101(4):734
D. P. O'Brien et al (see record 1995-08272-001) argue that the mental model theory of propositional reasoning is easy to refute, and they report 3 experiments that they believe falsify the theory. In contrast, L. Bonatti (see record 1995-08253-001) argues that the model theory is too flexible to be falsified. It is shown that the experiments by O'Brien et al do not refute the model theory and that Bonatti's claims are ill founded. Formal rule theories of propositional reasoning have 3 major weaknesses in comparison with the model theory: (1) They have no decision procedure; (2) they lack predictive power, providing no account of several robust phenomena (e.g., erroneous conclusions tend to be consistent with the premises); and (3) as a class of theories, they are difficult to refute experimentally. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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The modulation characteristics of DFB semiconductor lasers have been studied using a transfer matrix method combined with an appropriate rate equation analysis. The model takes into account longitudinal mode spatial hole burning, as well as the nonuniform current injection resulting from the axially varying Fermi voltage, and can be used for the efficient simulation of static, small-signal, and large-signal dynamic properties. The program is applied to the interpretation of experimental data from a strongly coupled InGaAsP/InP DFB laser. The experimental high-frequency properties of this device are well described by the simulations 相似文献