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The evidence base for drug treatment of hypertension is strong. Early trials using thiazide diuretics suggested a shortfall in prevention of coronary heart disease. The superiority of newer drugs has been widely advocated but trial evidence does not support an advantage of beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers or alpha-blockers for this outcome. Even meta-analyses have failed to clarify matters. If this issue is to be settled, bigger and better trials of longer duration in high-risk patients are needed. Meanwhile, the importance of rigorous blood pressure control using multiple drugs has been established. This should be the focus of our attention rather than agonising over differences in cause-specific outcomes that may not be generalisable to all patient populations.  相似文献   

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PURPOSE OF REVIEW: Although findings obtained from various studies are inconclusive in determining whether plasma platelet-activating factor acetylhydrolase, or lipoprotein-associated phospholipase A2, plays a proatherogenic or antiatherogenic role in atherosclerosis, many recent reviews appear to favor it as a risk factor for coronary artery disease. To provide a contrasting view, this review focuses on the enzyme's antiatherogenic and antiinflammatory properties. RECENT FINDINGS: A recent report demonstrates that plasma platelet-activating factor acetylhydrolase activity increases in men and women with stable angina or acute coronary syndromes, supporting previously published data that plasma levels of the protein are independently and positively associated with the risk of coronary artery disease. In contrast, at least four lines of evidence indicate that the enzyme has strong antiatherogenic properties: (1) it inhibits the effects of LDL oxidation, (2) genetic deficiency of plasma levels constitutes a risk factor for vascular diseases including atherosclerosis, (3) adenoviral transfer of the protein reduces atherosclerosis in apolipoprotein E-deficient mice, and (4) pretreatment of an electronegative LDL subfraction isolated from hypercholesterolemic human plasma with a recombinant platelet-activating factor acetylhydrolase completely abolishes the proapoptotic effects of the electronegative LDL on vascular endothelial cells. Additionally, treatment with the recombinant product reduced mortality from severe sepsis in a phase IIb clinical trial. In an animal study, transfection of tumor cells with platelet-activating factor acetylhydrolase inhibited tumor growth at the site of implantation. SUMMARY: Plasma platelet-activating factor acetylhydrolase becomes progressively activated as atherosclerosis progresses, but lines of evidence indicate that the enzyme possesses potent antiatherogenic and antiinflammatory properties. This raises the question of whether increased activity is a cause or a result of atherosclerosis and, consequently, whether inhibiting the enzyme's activities may decelerate or accelerate the progress of the disease.  相似文献   

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Recently, a novel gene was reported to underlie asthma. Linkage to the short arm of chromosome 20 in a genome screen was followed by positive tests of association that centre on the gene for a membrane-anchored zinc-dependent metalloproteinase known as ADAM33. The domain structure of the ADAM33 protein gives capabilities of proteolysis, adhesion, cell fusion and intracellular signalling. Although its function is at present unknown, these potential actions of ADAM33 provide many possibilities for further research.  相似文献   

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To tell the truth, I find it difficult to work when flying, or even when sitting in an airport for an extended period of time. So, typically I take along a book to read. And when I truly cannot concentrate, for example when a flight is considerably delayed, I have even been known to resort to word puzzles. Depending on the type, they do not require much attention (that is, you can pick up right where you left off after you glance at the flight status screen for the twentieth or so time, even though you know nothing has changed), or effort (although you need to use a pen or pencil, not a keyboard), but nonetheless they can keep your mind somewhat occupied. I even rationalize doing them based on the assumption that they are sharpening my observational/pattern-finding skills. One type of word puzzle that is particularly mindless, but for that very reason I still enjoy in the above circumstances, is a word search; you are given a grid with letters and/or numbers, and a list of “hidden” terms, and you circle them within the grid, crossing them off the list as you go along. I do admit that the categories of terms used in the typical word searches can become rather mundane (breeds of dog, types of food, words that are followed by “stone,” words associated with a famous movie star, words from a particular television show, etc.). Therefore, on one of my last seminar trips I decided to generate my own word search, using the category of autophagy.  相似文献   

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Restoration of coastal habitat fragmented, degraded, or destroyed by development and climate‐related processes such as sea level rise and storm surge usually involves planting native plants to restore habitat structure, but whether and how restored areas benefit taxa other than plants is rarely reported. Installing restoration plantings is one method used to build habitat such as beach dunes where dunes have been lost, potentially creating habitat for dune‐dependent species. We compared use of natural vegetated dunes, open sand gaps, and restoration plantings (habitat treatment) by Perdido Key beach mice (Peromyscus polionotus trissyllepsis) over 3 years using tracking tubes to assess the value of restoration plantings for beach mice. Tubes were monitored in two seasons (early and mid‐summer), and under new and full moon conditions. Mice used restoration plantings less than natural vegetated dunes but more than open sand gaps, which suggests restoration plantings may facilitate movement of mice across fragmented areas. Both season and moon phase influenced the effect of habitat treatment, interactions which may be attributable to perceived risk associated with movement under a combination of different conditions of ambient light, vegetation cover, and habitat novelty. Our results show restoration plantings provide habitat for movement and foraging, and may ameliorate some consequences of sea level rise and storms for beach mice and potentially other dune‐dependent species into the future.  相似文献   

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The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth, but a recent paper has also raised questions about how control of Cdc42 activity is integrated into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.  相似文献   

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This article presents one scientist''s perspective on the transition from life at the bench to an editorial career.  相似文献   

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Intercontinental disjunct distributions are a main issue in current biogeography. Bryophytes usually have broad distribution ranges and therefore constitute an interesting subject of study in this context. During recent fieldwork in western North America and eastern Africa, we found new populations of a moss morphologically similar to Orthotrichum acuminatum. So far this species has been considered to be one of the most typical epiphytic mosses of the Mediterranean Basin. The new findings raise some puzzling questions. Do these new populations belong to cryptic species or do they belong to O. acuminatum, a species which then has a multiple‐continent disjunct range? In the latter case, how could such an intercontinental disjunction be explained? To answer these questions, an integrative study involving morphological and molecular approaches was conducted. Morphological results reveal that Californian and Ethiopian samples fall within the variability of those from the Mediterranean Basin. Similarly, phylogenetic analyses confirm the monophyly of these populations, showing that O. acuminatum is one of the few moss species with a distribution comprising the western Nearctic, the western Palaearctic and Palaeotropical eastern Africa. Pending a further genetic and phylogeographical study to support or reject the hypothesis, a process of long‐distance dispersal (LDD) is hypothesized to explain this distribution and the origin of the species is suggested to be the Mediterranean Basin, from where diaspores of the species may have migrated to California and Ethiopia. The spore release process in O. acuminatum is revisited to support the LDD hypothesis, © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2016, 180 , 30–49.  相似文献   

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