81,378 research outputs found
[Letter from George M. Cox to T. N. Carswell - November 27, 1941]
No full textA letter written to Mr. T. N. Carswell, Parramore Post No. 57, American Legion, Abilene, Texas, from George M. Cox, Executive Editor, The Mobile Press Register, Mobile, Alabama, dated November 27, 1941. George M. Cox defines Americanism
Letter from W. T. Johnson to Miss Bessie M. Cox
No full textLetter from W. T. Johnson to Miss Bessie M. Cox, concerning Jamison Federation meeting
Letter from W. T. Johnson to Miss Bessie M. Cox, Supervisor, Lenoir County Schools
No full textLetter from W. T. Johnson to Miss Bessie M. Cox, Supervisor of Lenoir County Schools, concerning Jamison Federation meeting
Selective COX-2 inhibitors and risk of myocardial infarction
No full textSelective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel
Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2 - A mechanistic approach to the design of COX-1 selective agents
No full textResveratrol (3,4', 5- trihydroxy- trans- stilbene) is a phytoalexin found in grapes that has anti- inflammatory, cardiovascular protective, and cancer chemopreventive properties. It has been shown to target prostaglandin H-2 synthase (COX)-1 and COX-2, which catalyze the first committed step in the synthesis of prostaglandins via sequential cyclooxygenase and peroxidase reactions. Resveratrol discriminates between both COX isoforms. It is a potent inhibitor of both catalytic activities of COX-1, the desired drug target for the prevention of cardiovascular disease, but only a weak inhibitor of the peroxidase activity of COX-2, the isoform target for nonsteroidal anti- inflammatory drugs. We have investigated the unique inhibitory properties of resveratrol. We find that it is a potent peroxidase- mediated mechanism-based inactivator of COX-1 only (k(inact) = 0.069 +/- 0.004 s(-1), K-i( inact) = 1.52 +/- 0.15 muM), with a calculated partition ratio of 22. Inactivation of COX-1 was time- and concentration- dependent, it had an absolute requirement for a peroxide substrate, and it was accompanied by a concomitant oxidation of resveratrol. Resveratrol-inactivated COX-1 was devoid of both the cyclooxygenase and peroxidase activities, neither of which could be restored upon gel- filtration chromatography. Inactivation of COX-1 by [H-3] resveratrol was not accompanied by stable covalent modification as evident by both SDS-PAGE and reverse phase- high performance liquid chromatography analysis. Structure activity relationships on methoxy- resveratrol analogs showed that the m-hydroquinone moiety was essential for irreversible inactivation of COX-1. We propose that resveratrol inactivates COX-1 by a hit- and- run mechanism, and offers a basis for the design of selective COX-1 inactivators that work through a mechanism- based event at the peroxidase active site
Implementation of complex interactions in a Cox regression framework
No full textThe standard Cox proportional hazards model has been extended by functionally describable interaction terms. The first of which are related to neural networks by adopting the idea of transforming sums of weighted covariables by means of a logistic function. A class of reasonable weight combinations within the logistic transformation is described. Apart from the standard covariable product interaction, a product of logistically transformed covariables has also been included in the analysis of performance of the new terms. An algorithm combining likelihood ratio tests and AIC criterion has been defined for model choice. The critical values of the likelihood ratio test statistics had to be corrected in order to guarantee a maximum type I error of 5% for each interaction term. The new class of interaction terms allows interpretation of functional relationships between covariables with more flexibility and can easily be implemented in standard software packages
Concentration in Knowledge Output: A case of Economics Journals
No full textThis paper assesses the degree of author concentration in seven economics journals, which were published in India during 1990-2002. To measure the degree of author concentration, Lotka's Law was used. Moreover, we also make an exploratory analysis of the geographic, economics subfield and institutional concentration in 704 economics journals. An important finding of this paper is that specialized journals in the sample report the highest degree of author concentration. This result is quite similar to the findings by Cox and Chung (1991). Furthermore, there are several instances showing that the journals lean towards certain norms; this may affect the flow of innovative ideas into economics. We conclude that a knowledge activity, involving the high degree of concentration and a biased publication process, may affect the flow of new ideas into the discipline.Concentration, Lotka's Law
BOX-COX TRANSFORMATIONS AND ERROR TERM SPECIFICATION IN DEMAND MODELS
No full textThis paper analyzes the influence of error-term specification and functional form on a quarterly demand model for beef. The Box-Cox transformation is used to generalize the functional form while the equation error term is postulated to be both heteroskedastic and autoregressive. Results indicated that both functional form and error-term specification can play a major role in elasticity estimation, elasticity behavior, and hypothesis testing.Demand and Price Analysis,
Increased COX-2, but not COX-1, mRNA expression in Helicobacter Pylori gastritis
No full textThis study was designed to evaluate COX-1 and COX-2 mRNA expression in the gastric mucosa of H. pylori-infected and noninfected subjects. We confirmed and extended our previous observation that H. pylori up-regulated COX-2 mRNA expression and activity in gastric mucosal cells in vitro. Based on our studies, we postulate that activation of COX-2-related events during H. pylori infection may play a role in the multistep process leading to gastric cancer. Novel NSAIDs have recently been designed that selectively inhibit COX-2 at the site of inflammation without affecting COX-1–dependent generation of gastroprotective PGs. Therefore, one may envision the chemopreventive use of selective COX-2 inhibitors in those H. pylori-infected subjects who are resistant to conventional eradication regimens and potentially at risk for developing gastric cancer
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