Publications
173 results found
Mumby S, Ramakrishnan L, Evans TW, et al., 2014, Methemoglobin-induced signaling and chemokine responses in human alveolar epithelial cells, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 306, Pages: L88-L100, ISSN: 1040-0605
Nikolakopoulou Z, Smith M, Hector LR, et al., 2013, S100A12 AS A BIOMARKER FOR NEUTROPHIL MEDIATED INFLAMMATION IN PATIENTS UNDERGOING CARDIAC SURGERY NECESSITATING CARDIOPULMONARY BYPASS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A141-A141, ISSN: 0040-6376
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- Citations: 2
Ramakrishnan L, Mumby S, Meng C, et al., 2013, IL-6 mediated proliferative responses in human pulmonary vascular cells are differentially modulated by Iron/Heme/Hemoglobin, ERS 2013 Annual Congress
Pulmonary Arterial Hypertension (PAH) is characterised by progressive pulmonary vascular remodelling culminating in heart failure. Disrupted iron metabolism and anaemia have been linked to development of PAH suggesting iron supplementation may be beneο¬ cial. However iron compounds are known proliferative agents. IL-6 which is both proinο¬ ammatory and central to iron homeostasis is elevated in PAH. With emerging evidence of minor hemolysis in PAH patients, the availability of heme and/or haemoglobin (Hb) to PVCs may further impact on cellular responses. We aim to address the above issues in this study.Human pulmonary arterial smooth muscle cells (PASMCs) & endothelial cells (PAECs) were exposed to iron (FAC)/Heme/Hb prior to treatment with IL6. Cell proliferation was quantiο¬ed by Cyquant. RTPCR for expression of Hepcidin (regulatory hormone), Ferroportin (exporter), HO1, CD163(Hb scavenger) was also performed.IL-6 alone caused proliferation reversed by iron in PASMCs but not in PAECs. Heme restricted while Hb supported proliferation in both cell types. Basal CD163 mRNA was undetectable in PAECs but induced by IL-6. Hepcidin, Ferroportin and HO1 were also contrastingly regulated by IL6.[table1]Thus PVCs respond distinctly to the IL-6 stimulus which is further modulated by the availability of Iron/Heme/Hb. Besides IL-6 differentially regulated mRNA expression of genes involved in iron homeostasis. Further investigation of iron handling in PVCs seems warranted.
Creagh-Brown BC, Quinlan GJ, Hector LR, et al., 2013, Association between preoperative plasma sRAGE levels and recovery from cardiac surgery, Mediators of Inflammation, Vol: 2013, Pages: 1-7, ISSN: 0962-9351
Background. The receptor for advanced glycation end products (RAGE) is an inflammation-perpetuating receptor, and solubleRAGE (sRAGE) is a marker of cellular RAGE expression. This study investigated whether raised plasma levels prior to surgery ofsRAGE or S100A8/A9 (a RAGE ligand) were associated with longer duration of hospital care in patients undergoing cardiac surgerynecessitating cardiopulmonary bypass. Methods. Patients (π = 130) undergoing elective cardiac surgery were enrolled prospectively.Plasma sRAGE and S100A8/A9 concentrations were measured before and 2 h after surgery. Results. Preoperative plasma sRAGEincreased significantly (π < 0.0001) from 1.06 ng/mL (IQR, 0.72–1.76) to 1.93 ng/mL (IQR, 1.14–2.63) 2 h postoperatively. PlasmaS100A8/9 was also significantly (π < 0.0001) higher 2 h postoperatively (2.37 πg/mL, IQR, 1.81–3.05) compared to pre-operativelevels (0.41 πg/mL, IQR, 0.2–0.65). Preoperative sRAGE, but not S100A8/A9, was positively and significantly correlated withduration of critical illness (π = 0.3, π = 0.0007) and length of hospital stay (LOS; π = 0.31, π < 0.0005). Multivariate binarylogistic regression showed preoperative sRAGE to be, statistically, an independent predictor of greater than median duration ofcritical illness (odds ratio 16.6, π = 0.014) and to be, statistically, the strongest independent predictor of hospital LOS. Conclusion.Higher preoperative plasma sRAGE levels were associated with prolonged duration of care in adults undergoing cardiac surgeryrequiring cardiopulmonary bypass.
Davidson SJ, Britton G, Mumby S, et al., 2013, Neutrophil extracellular traps (NETs) and factor XII activation; a possible mechanism for increasing thrombotic risk during extracorporeal membrane oxygenation (ECMO), JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 430-430, ISSN: 1538-7933
Nikolakopoulou Z, Creagh-Brown B, Burke-Gaffney A, et al., 2013, Decreased expression of receptor for advanced glycation end-products (RAGE) on neutrophils following surgery necessitating cardiopulmonary bypass (snCPB), 100th Annual Meeting of the American-Association-of-Immunologists, Publisher: AMER ASSOC IMMUNOLOGISTS, ISSN: 0022-1767
Conway FM, Gordon SE, Mumby SJ, et al., 2012, The relationship of biochemical indices to the systemic inflammatory response syndrome following cardiac surgery. Time for SIRS to bow out?, Am J Respir Crit Care Med, American Thoracic Society, Pages: A1656-A1656
Conway FM, Gordon SE, Quinlan GJ, et al., 2011, DOES MEETING THE CLINICAL CRITERIA FOR THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME EQUATE TO BIOCHEMICAL INFLAMMATION FOLLOWING CARDIAC SURGERY?, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A96-A97, ISSN: 0040-6376
Mumby S, Chung KF, McCreanor JE, et al., 2011, Pro-oxidant iron in exhaled breath condensate: A potential excretory mechanism, RESPIRATORY MEDICINE, Vol: 105, Pages: 1290-1295, ISSN: 0954-6111
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- Citations: 10
Bastin AJ, Sato H, Davidson SJ, et al., 2011, Biomarkers of lung injury after one-lung ventilation for lung resection, RESPIROLOGY, Vol: 16, Pages: 138-145, ISSN: 1323-7799
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- Citations: 15
Hector LR, Lagan AL, Melley DD, et al., 2011, Polymorphisms in the haptoglobin gene predispose patients to adverse outcome after surgery necessitating cardiopulmonary bypass, Am J Respir Crit Care Med, American Thoracic Society International Congress, Pages: A1161-A1161
Leaver SK, Quinlan GJ, Evans TW, et al., 2010, THIOREDOXIN MODIFIES MIF RELEASE FROM HUMAN MONOCYTES FOLLOWING STIMULATION WITH LTA AND LPS, British-Thoracic-Society-Winter-Meeting 2010, Publisher: B M J PUBLISHING GROUP, Pages: A25-A26, ISSN: 0040-6376
Zakeri N, Creagh-Brown B, Hector LR, et al., 2010, POLYMORPHISMS IN GENES ENCODING RAGE OR RAGE LIGANDS PREDISPOSE PATIENTS TO ADVERSE OUTCOMES FOLLOWING SURGERY NECESSITATING CARDIOPULMONARY BYPASS, British-Thoracic-Society-Winter-Meeting 2010, Publisher: B M J PUBLISHING GROUP, Pages: A49-A49, ISSN: 0040-6376
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- Citations: 1
Creagh-Brown BC, Quinlan GJ, Evans TW, et al., 2010, The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: an important therapeutic target?, INTENSIVE CARE MEDICINE, Vol: 36, Pages: 1644-1656, ISSN: 0342-4642
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- Citations: 55
Quinlan GJ, 2010, Oxidative damage to extracellular proteins and lipids during acute lung injury.
Creagh-Brown BC, Quinlan GJ, Evans TW, 2010, RAGE inhibition: Healthy or harmful?, CRITICAL CARE MEDICINE, Vol: 38, Pages: 1487-1490, ISSN: 0090-3493
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- Citations: 3
Leaver SK, MacCallum NS, Pingle V, et al., 2010, Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration inhibitory factor., Intensive Care Med, Vol: 36, Pages: 336-341, ISSN: 1432-1238
PURPOSE: To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis. METHODS: Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients. RESULTS: Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(-1), interquartile range (IQR) 68.7-155.6, n = 32] compared with that in healthy controls (49.5 ng ml(-1), IQR 31.4-71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(-1), IQR 36.9-63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(-1), IQR 9.5-15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(-1), IQR 7.3-10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels. CONCLUSION: Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis.
Lagan AL, Hewitt RJ, Melley DD, et al., 2010, Adverse Outcomes From Cardiac Surgery Requiring Cardiopulmonary Bypass: Influence Of Polymorphism In Genes Encoding A Panel Of Cytokines, Am J Respir Crit Care Med, American Thoracic Society International Congress, Pages: A1161-A1161
Creagh-Brown BC, Quinlan G, Evans TW, et al., 2010, Advanced Glycation End-Products, Release Of Their Soluble Receptors (es And SRAGE) And Relationship To CRP After Surgery Necessitating Cardiopulmonary Bypass, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 181, ISSN: 1073-449X
Creagh-Brown BC, Quinlan G, Evans TW, et al., 2010, The RAGE Ligand S100B Induces IL-8 Release From Whole Blood And Isolated Neutrophils, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 181, ISSN: 1073-449X
Bundy RE, Melley DD, Hector LR, et al., 2010, Albumin Inhibits Heme Mediated Delay Of Spontaneous Neutrophil Apoptosis, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Bastin AJ, Lagan AL, Mumby S, et al., 2010, Effect Of N-acetylcysteine In Preventing Inflammation After Lung Resection And One-Lung Ventilation. A Randomised Controlled Trial., Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 1
Hector LR, Lagan AL, Melley DD, et al., 2010, Hemoglobin Release, Genetic Polymorphism And Adverse Outcome From Surgery Necessitating Cardiopulmonary Bypass, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 181, ISSN: 1073-449X
Hewitt RJ, Melley DD, Hector LR, et al., 2009, POLYMORPHISMS IN INFLAMMATORY PATHWAY GENES PREDISPOSE PATIENTS TO ADVERSE OUTCOMES AFTER CARDIOPULMONARY BYPASS SURGERY, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A26-A27, ISSN: 0040-6376
Goode EF, Hector LR, Lagan AL, et al., 2009, INFLUENCE OF CARDIAC SURGERY UTILISING CARDIOPULMONARY BYPASS ON NEUTROPHIL-RELATED PROINFLAMMATORY RESPONSES, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A49-A49, ISSN: 0040-6376
Lagan AL, Quinlan GJ, Evans TW, 2009, Haem oxygenase-1 polymorphism and ARDS, friend and foe?, INTENSIVE CARE MEDICINE, Vol: 35, Pages: 1325-1327, ISSN: 0342-4642
Burke-Gaffney A, Evans TW, Quinlan GJ, 2009, Thioredoxin in sepsis: Just another biomarker or a plausible therapeutic target?, CRITICAL CARE MEDICINE, Vol: 37, Pages: 2304-2305, ISSN: 0090-3493
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- Citations: 6
Creagh-Brown BC, Hector L, Lagan A, et al., 2009, The Role of sRAGE in the Development of ALI after Surgery Necessitating Cardiopulmonary Bypass., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 179, ISSN: 1073-449X
Creagh-Brown BC, Hector L, Lagan A, et al., 2009, RAGE Ligands Are Implicated in the Development of SIRS after Surgery Necessitating Cardiopulmonary Bypass, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 179, ISSN: 1073-449X
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- Citations: 1
Hacking MB, Leaver SK, MacCallum NS, et al., 2008, EXTRACELLULAR THIOREDOXIN IS INCREASED IN PATIENTS WITH SEPSIS: A PROTECTIVE RESPONSE AGAINST RAISED PLASMA LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR?, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A70-A70, ISSN: 0040-6376
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