1,721,082 research outputs found
Endothelin system in human cardiovascular physiology and pathophysiology
No full textThe experiments presented here arose from an interest in endothelial function and, particularly,
a wish to better understand the pharmacology and physiology of the endothelin (ET) system in
human blood vessels in health, and the influence of cardiovascular disease on the ET system.
This work followed from the discovery of ET-1 as a peptide endothelial mediator of vascular
tone in 1988. Publications are grouped into sections representing different aspects of the work.Section 1 is concerned with exploring pharmacological responses to the ET family of peptides,
the sarafotoxin analogue peptides, and ET antagonists, in human blood vessels in vivo. This
was amongst the first work with ET-1 in humans, and certainly the first to use the sarafotoxins,
ET receptor antagonists and ET converting enzyme (ECE) inhibitors. After characterisation of
the pharmacological tools, it was possible to show clearly that endogenous ET-1 plays a
physiological role in the control of peripheral resistance and blood pressure in healthy humans,
suggesting important clinical applications for these agents. It was also shown that the ETA
receptor is the major vasocontrictor receptor and that the major role in health of the ETB
receptor is endothelium-dependent vasodilatation, enhancement of which may contribute to the
beneficial clinical attributes of ETA receptor antagonism. In addition, local ET-1 infusion in
the forearm circulation was shown to be a system whereby the clinical efficacy of systemically
administered ET receptor antagonists could be modelled pharmacodynamicallySections 2-4 cover work confirming the substantial clinical utility of ET receptor antagonists
and ECE inhibitors as vasodilators, particularly in essential hypertension, heart failure and renal
failure. Other work, following congenital heart surgery, suggests that a cautious approach may
be needed in some cases of pulmonary hypertension. Studies with neutral endopeptidase (NEP)
inhibitors show unequivocally, but unexpectedly, that these agents are peripheral
vasoconstrictors, and the evidence presented is consistent with this effect occurring because
endogenously generated vascular ET-1 is an important substrate for NEP.Section 5 contains some miscellaneous but related studies, together with a series of review
articles written from 1991-98 synthesising the literature at each stage and drawing conclusions
about potential areas of major clinical interest in cardiovascular diseasePUBLICATIONS: • SECTION 1: CARDIOVASCULAR PHYSIOLOGY, Papers 1-19 • 1. Clarke JG, Benjamin N, Larkin SW, Webb DJ, Davies GJ, Maseri A. Endothelin is a potent long-lasting vasoconstrictor in men. Am J Physiol 1989;257:H2033-5. • 2. Cockcroft JR, Clarke JG, Webb DJ. The effect of intra-arterial endothelin on resting blood flow and sympathetically mediated vasoconstriction in the forearm of man. Br J Clin Pharmacol 1991;31:521-4. • 3. Waugh CJ, Dockrell MEC, Haynes WG, Olverman HJ, Williams BC, Webb DJ. The potassium channel opener BRL 38227 inhibits binding of [l25I]-labelled endothelin-1 to rat cardiac membranes. Biochem Biophys Res Commun 1992;185:630-5. • 4. Haynes WG, Webb DJ. Endothelium dependent modulation of responses to endothelin-1 in human veins. Clin Sci 1993;84:427-33. • 5. Dockrell MEC, Haynes WG, Williams BC, Webb DJ. Endothelin-1 and aggregation of human platelets in vitro. J Cardiovasc Pharmacol 1993;22(suppl 8), S204-6. • 6. Haynes WG, Webb DJ. Venoconstriction to endothelin-1 in humans: role of calcium and potassium channels. Am J Physiol 1993;265:H1676-81. • 7. Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet 1994;344:852-4. • 8. Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETb receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 1995;92:357-63. • 9. Strachan FE, Haynes WG, Webb DJ. Endothelium-dependent modulation of venoconstriction to sarafotoxin S6c in human veins in vivo. J Cardiovasc Pharmacol 1995;26(suppl. 3):S 180-2. • 10. Smith PJW, McQueen DS, Webb DJ. The effect of cooling on the contractile response to endothelin-1 in small arteries from humans. J Cardiovasc Pharmacol 1995;26(suppl3):S230-2. • 11. Plumpton C, Haynes WG, Webb DJ, Davenport AP. Phosphoramidon inhibition of the in vivo conversion of big endothelin-1 to endothelin-1 in the human forearm. Br J Pharmacol 1995; 116:1821-8. • 12. Haynes WG, Moffat S, Webb DJ. An investigation into the direct and indirect venoconstrictor effects of endothelin-1 and big endothelin-1 in man. Br J Clin Pharmacol 1995;40:307-11. • 13. Haynes WG, Ferro CJ, O'Kane KPJ, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 1996;93:1860-70. • 14. Dockrell MEC, Webb DJ, Williams BC. Activation of the endothelin B receptor causes a dose-dependent accumulation of cyclic GMP in human platelets. Blood Coag Fibrinolysis 1996;7:178-80. • 15. Plumpton C, Ferro CJ, Haynes WG, Webb DJ, Davenport AP. The increase in human plasma immunoreactive endothelin but not big endothelin-1 or its C-terminal fragment induced by systemic administration of the endothelin antagonist TAK-044. Br J Pharmacol 1996;119:311-4. • 16. Haynes WG, Hand MH, Dockrell MEC, Eadington DW, Lee MR, Benjamin N, Webb DJ. Physiological role of nitric oxide in regulation of renal function in humans. Am J Physiol 1997;272:F364-71. • 17. Ferro CJ, Haynes WG, Johnston NR, Lomax CC, Newby DE, Webb DJ. The peptide endothelin receptor antagonist, TAK-044, produces sustained inhibition of endothelin1 mediated arteriolar vasoconstriction. Br J Clin Pharmacol 1997;44:377-383. • 18. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by
inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998;97:752-6. • 19. Strachan FE, Spratt JC, Wilkinson IB, Gray GA, Johnston NR, Webb DJ. Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men. Hypertension 1999;33:581-5. • SECTION 2: HYPERTENSION AND RENAL DYSFUNCTION Papers 20-24 | 20. Haynes WG, Hand MF, Johnstone HA, Padfield PL, Webb DJ. Direct and sympathetically mediated venoconstriction in essential hypertension: enhanced responses to endothelin-1. J Clin Invest 1994;94:1359-64. • 2 1. Sturrock NDC, Lang CC, MacFarlane LJ, Dockrell MEC, Ryan M, Webb DJ, Struthers AD. Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males. J Hypertens 1995;13:667-73. • 22. Hand MF, Haynes WG, Johnstone HA, Anderton JL, Webb DJ. Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. Kidney Int 1995;48:806-13. • 23. Ferro CJ, Spratt JCS, Haynes WG, Webb DJ. Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo. Circulation 1998;97:2323-30. • 24. Hand MH, Haynes WG, Webb DJ. Reduced endogenous endothelin-1-mediated vascular tone in chronic renal failure. Kidney Int 1999;55:613-20. • SECTION 3 | ISCHAEMIC HEART DISEASE Papers 25-27 |
25. Wieczorek I, Haynes WG, Webb DJ, Ludlam CA, Fox KAA. Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction: relation to cardiovascular outcome. Br Heart J 1994;72:436-41. • 26. Flaynes WG, Hamer DW, Robertson CE, Webb DJ. Plasma endothelin following
cardiac arrest: differences between survivors and non-survivors. Resuscitation 1994;27:117-22. • 27. Newby DE, Flint LL, Fox KAA, Boon NA, Webb DJ. Reduced responsiveness to endothelin-1 in peripheral resistance vessels of patients with syndrome X. J Am Coll Cardiol 1998;31:1585-90. •
SECTION 4 | HEART FAILURE AND PULMONARY HYPERTENSION Papers 28-30 | 28. Davidson NC, Coutie WJ, Webb DJ, Struthers AD. Hormonal and renal differences
between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure. Heart 1996;75:576-81. • 29. Love MP, Haynes WG, Gray GA, Webb DJ, McMurray JJV. Vasodilator effects of
endothelin-converting enzyme inhibition and endothelin ETA receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circulation 1996;94:2131-7. • 30. Prendergast B, Newby DE, Wilson LE, Webb DJ, Mankad PS. Early therapeutic experience with the endothelin antagonist, BQ-123, in pulmonary hypertension after congenital heart surgery. Heart 1999;82:505-8 • SECTION 5 | MISCELLANEOUS TOPICS AND REVIEWS Papers 31-34 and 35-46 | 31. Sanai L, Haynes WG, McKenzie A, Grant IS, Webb DJ. Endothelin production in sepsis and the adult respiratory distress syndrome. Intens Care Med 1996;22:52-6. • 32. Mickley EJ, Gray GA, Webb DJ. Activation of endothelin ETa receptors masks the constrictor role of endothelin ETg receptors in rat isolated small esenteric arteries. Br J Pharmacol 1997;120:1376-82. • 33. McEwan PE, Valdenaire O, Sutherland L, Webb DJ, Gray GA. A non-radioactive method for localization of endothelin receptor mRNA in situ. J Cardiovasc Pharmacol 1998;31(suppl l):S443-6. • 34. Smith PJW, Ferro CJ, McQueen DS, Webb DJ. Functional studies in small arteries do not support a primary role for endothelin in the pathogenesis of Raynaud's disease. J Cardiovasc Pharmacol 1998;31(suppl l):S473-6. • 35. Webb DJ. Endothelin receptors cloned, endothelin converting enzyme characterised and pathophysiology explored. TiPS 1991;12:43-6. • 36. Haynes WG, Webb DJ. The endothelin family of peptides: local hormones with diverse roles in health and disease. Clin Sci 1993;84:485-500. • 37. Haynes WG, Davenport AP, Webb DJ. Endothelin: progress in pharmacology and physiology. TiPS 1993;14:225-8. • 38. Kennedy RL, Haynes WG, Webb DJ. Endothelins as regulators of growth and function in endocrine tissues. Clin Endocrinol 1993;39:259-65. • 39. Webb DJ, Haynes WG. Endothelins come of age. Lancet 1993;342:1439-40. • 40. Webb DJ. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure: endothelin antagonism in heart failure. Circulation 1995;92:3372. • 41. Ferro CJ, Webb DJ. The clinical potential of endothelin receptor antagonists in
cardiovascular medicine. Drugs 1996;51:12-27. • 42. Gray GA, Webb DJ. The endothelin system and its potential as a therapeutic target in cardiovascular disease. Pharmacol Ther 1996;72:109-48. • 43. Newby DN, Webb DJ. The endothelin system in cardiovascular disease: discovery to drug development in under a decade. BMJ 1997;314:531-2. •
44. Webb DJ. Endothelin: from molecule to man [BPS Research Prize Lecture]. Br J Clin Pharmacol 1997;44:9-20. •
Webb DJ, Monge JC, Rabelink A, Yanagisawa M. Endothelin: new discoveries and rapid progress in the clinic. Trends Pharmacol Sci 1998;19:5-8. • 46. Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health
and disease. J Hypertens 1998;16:1081-98
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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