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166 results on '"Tennent, Glenys A."'

1. Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis

Author

Slamova, Ivana, Adib, Rozita, Ellmerich, Stephan, Golos, Michal R., Gilbertson, Janet A., Botcher, Nicola, Canetti, Diana, Taylor, Graham W., Rendell, Nigel, Tennent, Glenys A., Verona, Guglielmo, Porcari, Riccardo, Mangione, P. Patrizia, Gillmore, Julian D., Pepys, Mark B., Bellotti, Vittorio, Hawkins, Philip N., Al-Shawi, Raya, and Simons, J. Paul

Published
2021
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5. Proteolytic cleavage of Ser52Pro variant transthyretin triggers its amyloid fibrillogenesis

Author

Mangione, P. Patrizia, Porcari, Riccardo, Gillmore, Julian D., Pucci, Piero, Monti, Maria, Porcari, Mattia, Giorgetti, Sofia, Marchese, Loredana, Raimondi, Sara, Serpell, Louise C., Chen, Wenjie, Relini, Annalisa, Marcoux, Julien, Clatworthy, Innes R., Taylor, Graham W., Tennent, Glenys A., Robinson, Carol V., Hawkins, Philip N., Stoppini, Monica, Wood, Stephen P., Pepys, Mark B., and Bellotti, Vittorio

Published
2014

7. Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Author

Kolstoe, Simon E., Mangione, Palma P., Bellotti, Vittorio, Taylor, Graham W., Tennent, Glenys A., Deroo, Stéphanie, Morrison, Angus J., Cobb, Alexander J. A., Coyne, Anthony, McCammon, Margaret G., Warner, Timothy D., Mitchell, Jane, Gill, Raj, Smith, Martin D., Ley, Steven V., Robinson, Carol V., Wood, Stephen P., Pepys, Mark B., and Weatherall, David J.

Published
2010

13. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

Author

Bodin, Karl, Ellmerich, Stephan, Kahan, Melvyn C., Tennent, Glenys A., Loesch, Andrzej, Gilbertson, Janet A., Hutchinson, Winston L., Mangione, Palma P., Gallimore, J. Ruth, Millar, David J., Minogue, Shane, Dhillon, Amar P., Taylor, Graham W., Bradwell, Arthur R., Petrie, Aviva, Gillmore, Julian D., Bellotti, Vittorio, Botto, Marina, Hawkins, Philip N., and Pepys, Mark B.

Subjects
Care and treatment, Physiological aspects, Development and progression, Research, Health aspects, Glycoproteins -- Health aspects -- Physiological aspects -- Research, Amyloidosis -- Care and treatment -- Development and progression -- Research, Antibodies -- Research -- Physiological aspects -- Health aspects, Viral antibodies -- Research -- Physiological aspects -- Health aspects
Abstract

SAP is selectively concentrated in amyloid deposits by its avid binding to all amyloid fibril types (2,3). SAP binding stabilizes amyloid fibrils, protects them from proteolysis in vitro (5) and [...], Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries (1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present (1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation (1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous (1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP) (2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.

Published
2010
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17. Targeting C-reactive protein for the treatment of cardiovascular disease

Author

Pepys, Mark B., Hirschfield, Gideon M., Tennent, Glenys A., Ruth Gallimore, J., Kahan, Melvyn C., Bellotti, Vittorio, Hawkins, Philip N., Myers, Rebecca M., Smith, Martin D., Polara, Alessandra, Cobb, Alexander J. A., Ley, Steven V., Andrew Aquilina, J., Robinson, Carol V., Sharif, Isam, Gray, Gillian A., Sabin, Caroline A., Jenvey, Michelle C., Kolstoe, Simon E., Thompson, Darren, and Wood, Stephen P.

Abstract

Author(s): Mark B. Pepys (corresponding author) [1]; Gideon M. Hirschfield [1, 6]; Glenys A. Tennent [1]; J. Ruth Gallimore [1]; Melvyn C. Kahan [1]; Vittorio Bellotti [1, 6]; Philip N. [...]

Published
2006
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18. A systematic study of the effect of physiological factors on beta2-microglobulin amyloid formation at neutral pH

Author

Myers, Sarah L., Jones, Susan, Jahn, Thomas R., Morten, Isobel J., Tennent, Glenys A., Hewitt, Eric W., and Radford, Sheena E.

Subjects
Beta globulins -- Chemical properties, Amyloid beta-protein -- Chemical properties, Amyloid beta-protein -- Structure, Recombinant proteins -- Chemical properties, Recombinant proteins -- Structure, Biological sciences, Chemistry
Abstract

A systematic study of the effect of 11 physiologically relevant factors on beta2-microglubulin (beta2m) fibrillogenesis at pH 7.0 without denaturants is described. The factors that could facilitate formation of beta2m fibrils in and around the sites of amyloid deposition are identified by comparing the behavior of wild-type beta2m with the variants in the presence or absence of different additives and standardizing the assay for fibril formation.

Published
2006

24. Amyloid damage to islet β-cells in type 2 diabetes: hypoxia or pseudo-hypoxia?

Author

Bellotti, Vittorio, primary, Corazza, Alessandra, additional, Foglia, Beatrice, additional, Novo, Erica, additional, Simons, J. Paul, additional, Mangione, P. Patrizia, additional, Verona, Guglielmo, additional, Canetti, Diana, additional, Nocerino, Paola, additional, Obici, Laura, additional, Vanoli, Alessandro, additional, Paulli, Marco, additional, Giorgetti, Sofia, additional, Raimondi, Sara, additional, Al-Shawi, Raya, additional, Tennent, Glenys A., additional, Taylor, Graham W., additional, Gillmore, Julian D., additional, Pepys, Mark B., additional, and Parola, Maurizio, additional

Published
2019
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28. Bifunctional crosslinking ligands for transthyretin

Author

Mangione, Palma P, Deroo, Stéphanie, Ellmerich, Stephan, Bellotti, Vittorio, Kolstoe, Simon E, Wood, Stephen P, Robinson, Carol V, Smith, Martin D, Tennent, Glenys A, Broadbridge, Robert R J, Council, Claire C E, Thurston, Joanne R, Steadman, Victoria A, Vong, Antonio K, Swain, Christopher J, Pepys, Mark B, Taylor, Graham W, Mangione, Palma P, Deroo, Stéphanie, Ellmerich, Stephan, Bellotti, Vittorio, Kolstoe, Simon E, Wood, Stephen P, Robinson, Carol V, Smith, Martin D, Tennent, Glenys A, Broadbridge, Robert R J, Council, Claire C E, Thurston, Joanne R, Steadman, Victoria A, Vong, Antonio K, Swain, Christopher J, Pepys, Mark B, and Taylor, Graham W

Abstract

Wild-type and variant forms of transthyretin (TTR), a normal plasma protein, are amyloidogenic and can be deposited in the tissues as amyloid fibrils causing acquired and hereditary systemic TTR amyloidosis, a debilitating and usually fatal disease. Reduction in the abundance of amyloid fibril precursor proteins arrests amyloid deposition and halts disease progression in all forms of amyloidosis including TTR type. Our previous demonstration that circulating serum amyloid P component (SAP) is efficiently depleted by administration of a specific small molecule ligand compound, that non-covalently crosslinks pairs of SAP molecules, suggested that TTR may be also amenable to this approach. We first confirmed that chemically crosslinked human TTR is rapidly cleared from the circulation in mice. In order to crosslink pairs of TTR molecules, promote their accelerated clearance and thus therapeutically deplete plasma TTR, we prepared a range of bivalent specific ligands for the thyroxine binding sites of TTR. Non-covalently bound human TTR-ligand complexes were formed that were stable in vitro and in vivo, but they were not cleared from the plasma of mice in vivo more rapidly than native uncomplexed TTR. Therapeutic depletion of circulating TTR will require additional mechanisms., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

29. Is leptin an important physiological regulator of CRP?

Author

Hutchinson, Winston L., Coll, Anthony P., Gallimore, J Ruth, Tennent, Glenys A., and Pepys, Mark B.

Abstract

Author(s): Winston L Hutchinson [1, 3]; Anthony P Coll [2, 3]; J Ruth Gallimore [1]; Glenys A Tennent [1]; Mark B Pepys [1] To the Editor: Binding between C-reactive protein [...]

Published
2007
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30. Bifunctional crosslinking ligands for transthyretin

Author

Mangione, P. Patrizia, primary, Deroo, Stéphanie, additional, Ellmerich, Stephan, additional, Bellotti, Vittorio, additional, Kolstoe, Simon, additional, Wood, Stephen P., additional, Robinson, Carol V., additional, Smith, Martin D., additional, Tennent, Glenys A., additional, Broadbridge, Robert J., additional, Council, Claire E., additional, Thurston, Joanne R., additional, Steadman, Victoria A., additional, Vong, Antonio K., additional, Swain, Christopher J., additional, Pepys, Mark B., additional, and Taylor, Graham W., additional

Published
2015
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32. C‐reactive protein is essential for innate resistance to pneumococcal infection

Author

Paul Simons, J., primary, Loeffler, Jutta M., additional, Al‐Shawi, Raya, additional, Ellmerich, Stephan, additional, Hutchinson, Winston L., additional, Tennent, Glenys A., additional, Petrie, Aviva, additional, Raynes, John G., additional, de Souza, J. Brian, additional, Lawrence, Rachel A., additional, Read, Kevin D., additional, and Pepys, Mark B., additional

Published
2014
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33. Novel palindromic ligands cementing the native quaternary structure of transthyretin

Author

Mangione, Palma P, Bellotti, Vittorio, Deroo, Stéphanie, Taylor, Graham W, McCammon, Margaret G, Robinson, Carol V, Tennent, Glenys A, Smith, Martin D, Morrison, Angus J, Cobb, Alexander J A, Coyne, Anthony, Ley, Steven V., Wood, Stephen P, Pepys, Mark B, Mangione, Palma P, Bellotti, Vittorio, Deroo, Stéphanie, Taylor, Graham W, McCammon, Margaret G, Robinson, Carol V, Tennent, Glenys A, Smith, Martin D, Morrison, Angus J, Cobb, Alexander J A, Coyne, Anthony, Ley, Steven V., Wood, Stephen P, and Pepys, Mark B

Abstract

info:eu-repo/semantics/published

Published
2010

34. Trapping of palindromic ligands within native transthyretin prevents amyloid formation.

Author

Kolstoe, Simon E, Mangione, Palma P, Bellotti, Vittorio, Taylor, Graham W, Tennent, Glenys A, Deroo, Stéphanie, Morrison, Angus J, Cobb, Alexander J A, Coyne, Anthony, McCammon, Margaret G, Warner, Timothy D, Mitchell, Janet, Gill, Raj, Smith, Martin D, Ley, Steven V., Robinson, Carol V, Wood, Stephen P, Pepys, Mark B, Kolstoe, Simon E, Mangione, Palma P, Bellotti, Vittorio, Taylor, Graham W, Tennent, Glenys A, Deroo, Stéphanie, Morrison, Angus J, Cobb, Alexander J A, Coyne, Anthony, McCammon, Margaret G, Warner, Timothy D, Mitchell, Janet, Gill, Raj, Smith, Martin D, Ley, Steven V., Robinson, Carol V, Wood, Stephen P, and Pepys, Mark B

Abstract

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2010

35. Targeting C-reactive protein for the treatment of cardiovascular disease

Author

Pepys, Mark B, Hirschfield, Gideon M, Tennent, Glenys A, Gallimore, J Ruth, Kahan, Melvyn C, Bellotti, Vittorio, Hawkins, Philip N, Myers, Rebecca M, Smith, Martin D, Polara, Alessandra, Cobb, Alexander J. A, Ley, Steven V, Aquilina, J. Andrew, Robinson, Carol V, Sharif, Isam, Gray, Gillian A, Sabin, Caroline A, Jenvey, Michelle C, Kolstoe, Simon E, Thompson, Darren, Wood, Stephen P, Pepys, Mark B, Hirschfield, Gideon M, Tennent, Glenys A, Gallimore, J Ruth, Kahan, Melvyn C, Bellotti, Vittorio, Hawkins, Philip N, Myers, Rebecca M, Smith, Martin D, Polara, Alessandra, Cobb, Alexander J. A, Ley, Steven V, Aquilina, J. Andrew, Robinson, Carol V, Sharif, Isam, Gray, Gillian A, Sabin, Caroline A, Jenvey, Michelle C, Kolstoe, Simon E, Thompson, Darren, and Wood, Stephen P

Abstract

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement1, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively2,3. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement4. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Published
2006

37. Reply

Author

Pepys, Mark B., primary, A. Tennent, Glenys, additional, and Denton, Christopher P., additional

Published
2007
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43. CLINICAL AND BIOCHEMICAL OUTCOME OF HEPATORENAL TRANSPLANTATION FOR HEREDITARY SYSTEMIC AMYLOIDOSIS ASSOCIATED WITH APOLIPOPROTEIN AI Gly26Arg1

Author

Gillmore, Julian D., primary, Stangou, Arie J., additional, Tennent, Glenys A., additional, Booth, David R., additional, O???Grady, John, additional, Rela, Mohamed, additional, Heaton, Nigel D., additional, Wall, Catherine A., additional, Keogh, J.A. Brian, additional, and Hawkins, Philip N., additional

Published
2001
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