Search

Your search keyword '"Axford, John"' showing total 327 results
Start Over Author "Axford, John"
327 results on '"Axford, John"'

4. Lymphocytic galactosyltransferase in rheumatoid arthritis and other diseases

Author

Axford, John Stewart

Subjects
572
Abstract

IgG-Fc galactose (IgG-gal) levels varies with age and reduced serum IgG-gal values have been reported in a restricted number of diseases: rheumatoid arthritis (RA), tuberculosis (TB), Crohn's disease and SLE associated with Sjogren's syndrome. The experimental objective of this study was to determine whether lymphocytic galactosyltransferase (GTase), the enzyme responsible for the transfer of galactose to IgG-Fc within the lymphocytic golgi, is defective in RA, and other diseases, and if it is causally related to IgG carbohydrate abnormalities. A reliable and reproducible assay of lymphocytic GTase, detecting the transfer of radiolabelled galactose to an acceptor glycoprotein, was devised, with a coefficient of variability of 4.4% and the ability to detect GTase from about 5x105 cells. Preliminary experiments with human GTase showed that activity could be detected in RA and control lymphocytes, serum and plasma, although no correlation existed between serum and lymphocytic levels in RA. A control age-matched population (n=32), without autoimmune disease, was used throughout for comparison. In all, except three, IgG-gal values were within 2 standard deviations of the normal mean for the age. No age relationship between IgG-gal and GTase activity was found in the control population. A wide range of GTase activities was noted in the control population and IgG-Fc galactosylation was positively correlated with GTase activity. A similar level of GTase activity was observed in B cell enriched preparations from human tonsils. The GTase activity in whole mononuclear cell preparations, from patients with RA, was significantly elevated. However, removal of monocytes, resulted in a fall in GTase activity, and B and T GTase activities were both reduced when measured individually when compared to healthy controls. This may indicate that T cell glycoproteins could be affected in a similar manner as IgG. A positive correlation between B and T cell GTase activity and a negative correlation between IgG-gal and B and T cell GTase was found. On splitting the rheumatoid arthritis population into groups, dependent upon drug treatment, it was noted that those patients taking sulphasalazine (SASP) had higher mean levels of GTase than the other patients in the study. This effect was shown not to be due to disease activity and was therefore presumed to be related to the actions of SASP itself. SASP is known to have pharmacological potential to cause these effects. In an initial longitudinal analysis of glycosylation parameters in patients with rheumatoid arthritis, a temporal relationship with clinical activity was found. In addition, SASP was shown to maintain GTase levels in other patients. Abnormal GTase activity was observed in clinically inactive patients, which may indicate continuing subclinical cellular dysfunction. Although GTase activity was found to be normal in patients with osteoarthritis when compared to healthy controls, it was decreased in patients with SLE, Crohn's disease and active pulmonary TB. In only the TB patients did GTase return to normal with treatment. CD5 positive B cell GTase activity from patients with chronic lymphocytic leukaemia was determined and a significant decrease in GTase activity was noted when compared to a control population with the same age range. In an attempt to investigate the mechanism of fluctuations in GTase activity the presence of an intracellular inhibitor and specific polymorphisms within the gene encoding the GTase activator (GTA) gene, were looked for. Using normal GTase from human lymphocytes, bovine milk and human milk, no inhibition of activity was detected when mixed with RA lymphocyte extract. In one experiment, synergism was noted in both RA and normal preparations, which may indicate the presence of a co-factor in human lymphocytes. On restriction enzyme digestion of RA and normal lymphocytic DNA, no gross structural changes in the GTA gene was seen and hence gene abnormalities are also unlikely to be responsible for reduced GTase activity. RFLPs were, however, observed using the enzyme Bgl II in both normal and RA DNA. To test whether fluctuations in isoenzymes of GTase may be implicated in the abnormal glycosylation of IgG, and potentially other glycoproteins, GTase activity towards 5 different oligosaccharide acceptors was determined. A decrease in enzyme activity, comparable to ovalbumin, was noted only with asialo-mucin. In order that cells, other than those from the periphery, could be studied in disease, the MRL/lpr mouse, a model for rheumatoid arthritis, was used. GTase from pooled peripheral and splenic B cells was assayed from MRL/lpr, MRL+/+ and CBA/J (control) strains of mice. Splenic B cell GTase activity was found to be similar in both the MRL strains and the CBA/J control strain, whereas enzyme activity was reduced in the peripheral B cells only in the MRL strains. This may suggest that reduced GTase in the MRL mouse is one of a number of factors leading to disease in the lpr strain, which are not present in the +/+ strain, and is not a direct result of the disease itself. In conclusion, GTase activity has been studied in normal individuals and those with RA, SLE, TB, CD and CLL. Reduced levels of GTase are apparent in the presence of disease, irrespective of clinical activity, but in individuals with TB the GTase always returns to normal following antibiotic treatment and often does in patients with RA treated with SASP. There is no evidence to suggest that reduced GTase activity may be due to an intracellular inhibitor of GTase in RA, nor to gross structural changes in the GTA gene. Evidence is provided which suggests that GTase isoenzyme changes may occur in RA. A hypothesis is presented linking isoenzyme changes with glycoprotein abnormalities and the clinical presentation of disease. Similar GTase activity findings are reported in the peripheral, but not the splenic, B cells of the MRL (arthritic) mouse, suggesting that cells being sampled in the periphery are trafficing from areas of inflammation.

Published
1990

10. Meeting report on 14th Jenner Glycobiology and Medicine Symposium: glycobiology in immunology, medicine, and clinical practice

Author

O’Flaherty, Roisin, Opdenakker, Ghislain, Clausen, Henrik, Gerardy-Schahn, Rita, Kieda, Claudine, Reis, Celso A, Rudd, Pauline M, Sadrieh, Azita, Axford, John, O’Flaherty, Roisin, Opdenakker, Ghislain, Clausen, Henrik, Gerardy-Schahn, Rita, Kieda, Claudine, Reis, Celso A, Rudd, Pauline M, Sadrieh, Azita, and Axford, John

Abstract

The abstract is included in the text.

Published
2022

39. Lyme arthritis

Author

Rees, David H.E. and Axford, John S.

Subjects
Lyme disease -- Complications, Arthritis -- Diagnosis, Tick-borne diseases -- Care and treatment, Health
Abstract

Lyme arthritis may occur months or years after initial infection with Borrelia (B.) burgdorferi, the agent that causes Lyme disease. Ixodes ticks carrying B. burgdorferi are the main vectors (carriers that convey an infective agent to a host) of Lyme disease, making Lyme disease the most common vector-born disease in the U.S. Lyme disease may be successfully treated with antibiotics in its early stages. Arresting the disease in its early stages can prevent later complications such as arthritis, heart problems, and skin rashes. Arthritis may be the only symptom in some patients. It is suggested that blood tests for Lyme disease only be conducted if a patient has a history of exposure to tick-infested areas and symptoms typical of Lyme disease. Some patients may not respond to antibiotic treatments because of genetically caused autoimmune responses to B. burgdorferi infection.

Published
1994

40. Fever of unknown origin in childhood: difficulties in diagnosis

Author

Martin, Katherine, Davies, E. Graham, and Axford, John S.

Subjects
Rheumatic diseases in children -- Diagnosis, Fever in children -- Diagnosis, Health
Abstract

A 12-year-old boy with a fever of unknown origin was eventually diagnosed with systemic onset juvenile chronic arthritis (S-JCA). The boy was first misdiagnosed as having acquired toxoplasmosis due to a positive latex agglutination test for toxoplasma. Treatment of this presumed infection caused a severe allergic response with Stevens-Johnson syndrome, kidney failure and disseminated intravascular coagulation (DIC). The diagnosis of S-JCA was finally reached because of a high spiking daily fever, a characteristic rose-colored rash, and arthritis. The boy slowly improved after receiving 40 milligrams/day of prednisolone, which he was able to discontinue after the disease activity ended. Difficulties in diagnosing S-JCA and the usual features of the disease are discussed.

Published
1994

41. Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Author

Heathfield, Sarah, Parker, Ben, Zeef, Leo, Bruce, Ian, Alexander, Yvonne, Collins, Fraser, Stone, Michael, Wang, Edward, Williams, Anwen S., Wright, Helen L., Thomas, Huw B., Moots, Robert J., Edwards, Steven W., Bullock, Craig, Chapman, Victoria, Walsh, David A., Mobasheri, Ali, Kendall, David, Kelly, Sara, Bayley, Rachel, Buckley, Chris D., Young, Stephen P., Rump-Goodrich, Lisa, Middleton, Jim, Chen, Liye, Fisher, Roman, Kollnberger, Simon, Shastri, Nilabh, Kessler, Benedikt M., Bowness, Paul, Nazeer Moideen, Abdul, Evans, Laura, Osgood, Louise, Jones, Simon A., Nowell, Mari A., Mahadik, Younis, Young, Stephen, Morgan, Matthew, Gordon, Caroline, Harper, Lorraine, Giles, Joanna L., Paul Morgan, B., Harris, Claire L., Rysnik, Oliwia J., McHugh, Kirsty, Payeli, Sravan, Marroquin, Osiris, Shaw, Jacqueline, Renner, Christoph, Nayar, Saba, Cloake, Tom, Bombardieri, Michele, Pitzalis, Costantino, Buckley, Chris, Barone, Francesca, Lane, Peter, Coles, Mark, Williams, Emma L., Edwards, Christopher J., Cooper, Cyrus, Oreffo, Richard O., Dunn, Sara, Crawford, Aileen, Wilkinson, Mark, Le Maitre, Christine, Bunning, Rowena, Daniels, Jodie, Phillips, Kate L. E., Chiverton, Neil, Le Maitre, Christine L., Shaw, Jackie, Ridley, Anna, Wong-Baeza, Isabel, Keidel, Sarah, Chan, Antoni, Gullick, Nicola J., Abozaid, Hanan S., Jayaraj, David M., Evans, Hayley G., Scott, David L., Choy, Ernest H., Taams, Leonie S., Hickling, M., Golor, G., Jullion, A., Shaw, S., Kretsos, K., Bari, Syed F., Rhys-Dillon, Brian, Amos, Nicholson, Siebert, Stefan, Bunning, Rowena D., Haddock, Gail, Cross, Alison K., Kate, I., Phillips, E., Cross, Alison, Bunning, Rowena A. D., Ceeraz, Sabrina, Spencer, Jo, Choy, Ernest, Corrigall, Valerie, Crilly, Anne, Palmer, Helen, Lockhart, John, Plevin, Robin, Ferrell, William R., McInnes, Iain, Hutchinson, David, Perry, Liz, DiCicco, Maria, Humby, Frances, Kelly, Stephen, Hands, Rebecca, McInnes, Ian, Taylor, Peter, Mehta, Puja, Mitchell, Adam, Tysoe, Carolyn, Caswell, Richard, Owens, Martina, Vincent, Tonia, Hashmi, Tahir M., Price-Forbes, Alec, Sharp, Charlotte A., Murphy, Helen, Wood, Elizabeth F., Doherty, Teresa, Sheldon, Jo, Sofat, Nidhi, Goff, Iain, Platt, Philip N., Abdulkader, Rita, Clunie, Gavin, Ismajli, Mediola, Nikiphorou, Elena, Young, Adam, Tugnet, Nicola, Dixey, Josh, Banik, Snehashish, Alcorn, Desmond, Hunter, John, Win Maw, Win, Patil, Pravin, Hayes, Fiona, Main Wong, Way, Borg, Frances A., Dasgupta, Bhaskar, Malaviya, Anshuman P., Ostor, Andrew J., Chana, Jasroop K., Ahmed, Azeem A., Edmonds, Sally, Coward, Lucy, Borg, Frances, Heaney, Jonathan, Amft, Nicole, Simpson, John, Dhillon, Veena, Ayalew, Yezenash, Khattak, Fazlihakim, Gayed, Mary, Amarasena, Roshan I., McKenna, Frank, Mc Laughlin, Maeve, Baburaj, Krishnan, Fattah, Zozik, Ng, Nora, Wilson, Jo, Colaco, Bernard, Williams, Mark R., Adizie, Tochukwu, Casey, Matthew, Lip, Stefanie, Tan, Shaun, Anderson, David, Robertson, Calum, Devanny, Ian, Field, Max, Walker, David, Robinson, Sandra, Ryan, Sarah, Hassell, Andrew, Bateman, James, Allen, Maggie, Davies, David, Crouch, Carina, Walker-Bone, Karen, Gainsborough, Nicola, Lutalo, Pamela M., Davies, Ursula M., Mckew, Jennifer R., Millar, Auleen M., Wright, Stephen A., Bell, Aubrey L., Thapper, Muryum, Roussou, Thalia, Cumming, Jo, Hull, Richard G., McKeogh, John, O'Connor, Mortimer B., Hassan, Ahmed I., Bond, Ursula, Swan, Joan, Phelan, Mark J., Coady, David, Kumar, Namita, Farrow, Luke, Bukhari, Marwan, Oldroyd, Alexander G., Greenbank, Cathi, McBeth, John, Duncan, Rosie, Brown, Deborah, Horan, Michael, Pendleton, Neil, Littlewood, Alison, Cordingley, Lis, Mulvey, Matthew, Curtis, Elizabeth M., Cole, Zoe A., Crozier, Sarah R., Georgia, Ntani, Robinson, Siân M., Godfrey, Keith M., Sayer, Avan A., Inskip, Hazel M., Harvey, Nicholas C., Davies, Rebecca, Mercer, Louise, Galloway, James, Low, Audrey, Watson, Kath, Lunt, Mark, Symmons, Deborah, Hyrich, Kimme, Chitale, Sarang, Estrach, Cristina, Goodson, Nicola J., Rankin, Elizabeth, Jiang, C. Q., Cheng, K. K., Lam, T. H., Adab, Peymané, Ling, Stephanie, Humphreys, Jennifer, Ellis, Corrinne, Bunn, Diane, Verstappen, Suzanne M., Fluess, Elisa, Macfarlane, Gary J., Bond, Christine, Jones, Gareth T., Scott, Ian C., Steer, Sophia, Lewis, Cathryn M., Cope, Andrew, Mulvey, Matthew R., Lovell, Karina, Keeley, Philip, Woby, Steve, Beasley, Marcus, Viatte, Sebastien, Plant, Darren, Fu, Bo, Solymossy, Csilla, Worthington, Jane, Barton, Anne, Williams, Frances M., Osei-Bordom, Daniel-Clement, Popham, Maria, MacGregor, Alex, Spector, Tim, Little, Jayne, Herrick, Ariane, Pushpakom, S., Ennis, H., McBurney, H., Worthington, J., Newman, W., Ibrahim, Ibrahim, Morgan, Anne, Wilson, Anthony, Isaacs, John, Sanderson, Tessa, Hewlett, Sarah, Calnan, Michael, Morris, Marianne, Raza, Karim, Kumar, Kanta, Cardy, Caroline M., Pauling, John D., Jenkins, Jessica, Brown, Sue J., McHugh, Neil, Mugford, Miranda, Davies, Charlotte, Cooper, Nicola, Brooksby, Alan, Dures, Emma, Ambler, Nick, Fletcher, Debbie, Pope, Denise, Robinson, Frances, Rooke, Royston, Gorman, Claire L., Reynolds, Piero, Hakim, Alan J., Bosworth, Ailsa, Weaver, Dan, Kiely, Patrick D., Skeoch, Sarah, Jani, Meghna, Amarasena, Roshan, Rao, Chandini, Macphie, Elizabeth, McLoughlin, Yokemei, Shah, Preeti, Else, Sara, Semenova, Olga, Thompson, Helen, Ogunbambi, Olabambo, Kallankara, Sathish, Patel, Yusuf, Baguley, Elaine, Halsey, John, Severn, Andrew, Selvan, Shilpa, Price, Elizabeth, Husain, Muhammad J., Brophy, Sinead, Phillips, Ceri J., Cooksey, Roxanne, Irvine, Elizabeth, Lendrem, Dennis, Mitchell, Sheryl, Bowman, Simon, Pease, Colin T., Emery, Paul, Andrews, Jacqueline, Sutcliffe, Nurhan, Lanyon, Peter, Gupta, Monica, McLaren, John, Regan, Marian, Cooper, Annie, Giles, Ian, Isenberg, David, Griffiths, Bridget, Foggo, Heather, Edgar, Suzanne, Vadivelu, Saravanan, Ng, Wan-Fai, Iqbal, Itrat, Heron, Louise, Pilling, Claire, Marks, Jonathan, Hull, Richard, Ledingham, Jo, Han, Chenglong, Gathany, Tim, Tandon, Neeta, Hsia, Elizabeth, Taylor, P., Strand, V., Sensky, T., Harta, N., Fleming, S., Kay, Lesley, Rutherford, Michelle, Nicholl, Karl, Eyre, Tracey, Wilson, Gillian, Johnson, Phil, Russell, M., Timoshanko, J., Duncan, G., Spandley, A., Roskell, S., West, Louise, Adshead, Rebecca, Donnelly, Simon P., Ashton, Simon, Tahir, Hasan, Patel, Dipti, Darroch, James, Boulton, John, Ellis, Benjamin, Finlay, Ron, Murray-Brown, William, Priori, R., Tappuni, T., Vartoukian, S., Seoudi, N., Picarelli, G., Fortune, F., Valesini, G., Pitzalis, C., Bombardieri, M., Ball, Elisabeth, Rooney, Madeleine, Bell, Aubrey, Mérida, Angeles Acosta, Tarelli, Edward, Axford, John, Pericleous, Charis, Pierangeli, Silvia S., Ioannou, John, Rahman, Anisur, Alavi, Azita, Hughes, Michael, Evans, Bronwen, Zaki, Awal, Hui, Michelle, Garner, Rozeena, Rees, Frances, Bavakunji, Riaz, Daniel, Priya, Varughese, Sneha, Srikanth, Asha, Andres, Mariano, Pearce, Fiona, Leung, Jansen, Lim, Ken, Oomatia, Amin, Petri, Michelle, Fang, Hong, Birnbaum, Julius, Amissah-Arthur, Maame, Stewart, Kirsty, Jennens, Hannah, Braude, Simon, Sutton, Emily J., Watson, Kath D., Yee, Chee-Seng, Jayne, David, Akil, Mohammed, Ahmad, Yasmeen, D'Cruz, David, Khamashta, Munther, Teh, Lee-Suan, Zoma, Asad, Dey, Ida D., Kenu, Ernest, Garza-Garcia, Acely, Murfitt, Lucy, Driscoll, Paul C., Pierangeli, Silvia, Ioannou, Yiannis, Reynolds, John A., Ray, David W., O'Neill, Terence, Segeda, Iuliia, Shevchuk, Sergii, Kuvikova, Inna, Brown, Nina, Venning, Michael, Dhanjal, Mandish, Mason, Justin, Nelson-Piercy, Catherine, Basu, Neil, Paudyal, Priya, Stockton, Marie, Lawton, Sally, Dent, Caroline, Kindness, Kathy, Meldrum, Gillian, John, Elizabeth, Arthur, Catherine, West, Lucy, Macfarlane, Matthew V., Reid, David M., Yates, Max, Loke, Yoon, Watts, Richard, Christidis, Dimitrios, Williams, Mark, Sivakumar, Rajappa, Misra, Ramnath, Danda, Debashish, Mahendranath, K. M., Bacon, Paul A., and Mackie, Sarah L.

Abstract

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q < 0.00005). This was supported by qPCR analysis at 6 hrs (E-selectin and VCAM-1; 208.5 fold and 40.5, respectively above control) and also at 1, 3 and 24 hrs (E-selectin; 25.6, 93.5, 12.7 fold, respectively) (VCAM-1; 4.7, 47.2, 17.6 fold) (n = 3; p < 0.05). In contrast, HAoECs treated with TNF in combination with CZP exhibited control levels of E-selectin and VCAM-1 transcript (p > 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interest

Published
2017

44. The Role of Antigen in Autoimmune Responses with Special Reference to Changes in Carbohydrate Structure of IgG in Rheumatoid Arthritis

Author

Roitt, Ivan M., primary, Dwek, Raymond A., additional, Parekh, Rajesh B., additional, Rademacher, Thomas W., additional, Alavi, Azita, additional, Axford, John S., additional, Bodman, Katherine B., additional, Bond, Angela, additional, Cooke, Anne, additional, Hay, Frank C., additional, Isenberg, David A., additional, Lydyard, Peter M., additional, Mackenzie, Lorna, additional, Rook, Graham, additional, Smith, Mark, additional, and Sumar, Nazira, additional

Published
1989
Full Text
View/download PDF

46. Rheumatoid Arthritis is Associated with IgG Antibodies to Human Endogenous Retrovirus Gag Matrix: A Potential Pathogenic Mechanism of Disease?

Author

Nelson, Paul N., primary, Roden, Denise, additional, Nevill, Alan, additional, Freimanis, Graham L., additional, Trela, Malgorzata, additional, Ejtehadi, Hora Davari, additional, Bowman, Simon, additional, Axford, John, additional, Veitch, Andy M., additional, Tugnet, Nicola, additional, and Rylance, Paul B., additional

Published
2014
Full Text
View/download PDF

47. Meeting report on 14th Jenner Glycobiology and Medicine Symposium: glycobiology in immunology, medicine, and clinical practice.

Author

O'Flaherty, Roisin, Opdenakker, Ghislain, Clausen, Henrik, Gerardy-Schahn, Rita, Kieda, Claudine, Reis, Celso A, Rudd, Pauline M, Sadrieh, Azita, and Axford, John

Subjects
GLYCOCALYX, GLYCOMICS, GLYCOSAMINOGLYCANS, CONFERENCES & conventions, REGULATORY T cells
Abstract

The 14 SP th sp Jenner Glycobiology and Medicine Symposium took place at the Rega Institute, KU Leuven, in the beautiful city of Leuven, Belgium, last October 2021 (Fig. The Jenner Glycobiology and Medicine symposia were the first and main international multidisciplinary conferences set up to examine the relevance of glycobiology to immunology, medicine, and clinical practice. [Extracted from the article]

Published
2022
Full Text
View/download PDF

48. ETHEREAL BEAUTY.

Author

WHEATER, CAROLINE, Axford, John, and Bradlow, Robert

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results