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2. Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix Jo-Bamba, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H. Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J., Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice Ann, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P., Gallagher, Hugh, Game, David, Garcia, Eva Lozano, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P.J., Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A., Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Frankl, Fiona Karet, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P., Maggie Lai, Ling Wai, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J., Mark, Patrick B., Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM., Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J., Persu, Alexandre, Petchey, William G., Pickering, Matthew C., Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian SD., Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, R.N., Sandu, Kanwaljit S., Sarween, Nadia, Sayer, John A., Sebire, Neil, Selvaskandan, Haresh, Shah, Sapna, Sharma, Asheesh, Sharples, Edward J., Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A. Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B., Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin Iain, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H., Wilson, Patricia D., Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Griffin, Sian, Hall, Matt, Karet Frankl, Fiona, Maher, Eamonn R., Pinney, Jenny, Tam, Frederick W.K., Wilson, Patricia, Sy, Karla Therese L., Huang, Kui, Ye, Jamie, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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5. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J, Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P, Gallagher, Hugh, Game, David, Garcia, Eva, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P J, Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A, Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Karet Frankl, Fiona, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P, Lai, Ling Wai Maggie, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J, Mark, Patrick B, Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM, Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J, Persu, Alexandre, Petchey, William G, Pickering, Matthew C, Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian S D, Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, Richard, Sandu, Kanwaljit S, Sarween, Nadia, Sayer, John A, Sebire, Neil, Selvaskandan, Haresh, Sharma, Asheesh, Sharples, Edward J, Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B, Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin I, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H, Wilson, Patricia D, Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Chrysochou, Constantina, Griffin, Sian, Hall, Matt, Maher, Eamonn R, Pinney, Jenny, Tam, Frederick W K, Turner, Andrew Neil, Wilson, Patricia, Taylor, Christopher Mark, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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7. Autoantibody and T cell responses to oxidative post-translationally modified insulin neoantigenic peptides in type 1 diabetes

Author

Strollo, Rocky, Vinci, Chiara, Man, Y. K. Stella, Bruzzaniti, Sara, Piemonte, Erica, Alhamar, Ghadeer, Briganti, Silvia Irina, Malandrucco, Ilaria, Tramontana, Flavia, Fanali, Chiara, Garnett, James, Buccafusca, Roberto, Guyer, Perrin, Mamula, Mark, James, Eddie A., Pozzilli, Paolo, Ludvigsson, Johnny, Winyard, Paul G., Galgani, Mario, and Nissim, Ahuva

Published
2023
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9. Single‐cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease.

Author

Chandler, Jennifer C, Jafree, Daniyal J, Malik, Saif, Pomeranz, Gideon, Ball, Mary, Kolatsi‐Joannou, Maria, Piapi, Alice, Mason, William J, Benest, Andrew V, Bates, David O, Letunovska, Aleksandra, Al‐Saadi, Reem, Rabant, Marion, Boyer, Olivia, Pritchard‐Jones, Kathy, Winyard, Paul J, Mason, Andrew S, Woolf, Adrian S, Waters, Aoife M, and Long, David A

Subjects
TRANSCRIPTION factors, KIDNEY glomerulus diseases, ENDOTHELIAL cells, JUVENILE diseases, ADRENOMEDULLIN
Abstract

WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell‐types in the glomerulus. We hypothesised that this could be resolved using single‐cell RNA sequencing (scRNA‐seq) and ligand‐receptor analysis to profile glomerular cell–cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1R394W/+). Podocytes were the most dysregulated cell‐type in the early stages of Wt1R394W/+ disease, with disrupted angiogenic signalling between podocytes and the endothelium, including the significant downregulation of transcripts for the vascular factors Vegfa and Nrp1. These signalling changes preceded glomerular endothelial cell loss in advancing disease, a feature also observed in biopsy samples from human WT1 glomerulopathies. Addition of conditioned medium from murine Wt1R394W/+ primary podocytes to wild‐type glomerular endothelial cells resulted in impaired endothelial looping and reduced vascular complexity. Despite the loss of key angiogenic molecules in Wt1R394W/+ podocytes, the pro‐vascular molecule adrenomedullin was upregulated in Wt1R394W/+ podocytes and plasma and its further administration was able to rescue the impaired looping observed when glomerular endothelium was exposed to Wt1R394W/+ podocyte medium. In comparative analyses, adrenomedullin upregulation was part of a common injury signature across multiple murine and human glomerular disease datasets, whilst other gene changes were unique to WT1 disease. Collectively, our study describes a novel role for altered angiogenic signalling in the initiation of WT1 glomerulopathy. We also identify adrenomedullin as a proangiogenic factor, which despite being upregulated in early injury, offers an insufficient protective response due to the wider milieu of dampened vascular signalling that results in endothelial cell loss in later disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Synthesis and characterization of amine-functionalized graphene as a nitric oxide-generating coating for vascular stents.

Author

Tabish, Tanveer A., Hussain, Mian Zahid, Zhu, Yangzhi, Xu, Jiabao, Huang, Wei E., Diotallevi, Marina, Narayan, Roger J., Crabtree, Mark J., Khademhosseini, Ali, Winyard, Paul G., and Lygate, Craig A.

Subjects
FOURIER transform infrared spectroscopy, CORONARY artery disease, GRAPHENE oxide, ACCELERATED life testing, POLYETHYLENE glycol, POLYLACTIC acid, POLYETHYLENEIMINE
Abstract

Drug-eluting stents are commonly utilized for the treatment of coronary artery disease, where they maintain vessel patency and prevent restenosis. However, problems with prolonged vascular healing, late thrombosis, and neoatherosclerosis persist; these could potentially be addressed via the local generation of nitric oxide (NO) from endogenous substrates. Herein, we develop amine-functionalized graphene as a NO-generating coating on polylactic acid (PLA)-based bioresorbable stent materials. A novel catalyst was synthesized consisting of polyethyleneimine and polyethylene glycol bonded to graphene oxide (PEI-PEG@GO), with physicochemical characterization using x-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. In the presence of 10 μM S-nitrosoglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP), PEI-PEG@GO catalyzed the generation of 62% and 91% of the available NO, respectively. Furthermore, PEI-PEG@GO enhanced and prolonged real-time NO generation from GSNO and SNAP under physiological conditions. The uniform coating of PEI-PEG@GO onto stent material is demonstrated via an optimized simple dip-coating method. The coated PLA maintains good biodegradability under accelerated degradation testing, while the PEI-PEG@GO coating remains largely intact. Finally, the stability of the coating was demonstrated at room temperature over 60 days. In conclusion, the innovative conjugation of polymeric amines with graphene can catalyze the generation of NO from S-nitrosothiols at physiologically relevant concentrations. This approach paves the way for the development of controlled NO-generating coatings on bioresorbable stents in order to improve outcomes in coronary artery disease. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Description and cross-sectional analyses of 25,880 adults and children in the UK National Registry of Rare Kidney Diseases cohort

Author

Wong, Katie, primary, Pitcher, David, additional, Braddon, Fiona, additional, Downward, Lewis, additional, Steenkamp, Retha, additional, Masoud, Sherry, additional, Annear, Nicholas, additional, Barratt, Jonathan, additional, Bingham, Coralie, additional, Coward, Richard J., additional, Chrysochou, Tina, additional, Game, David, additional, Griffin, Sian, additional, Hall, Matt, additional, Johnson, Sally, additional, Kanigicherla, Durga, additional, Karet Frankl, Fiona, additional, Kavanagh, David, additional, Kerecuk, Larissa, additional, Maher, Eamonn R., additional, Moochhala, Shabbir, additional, Pinney, Jenny, additional, Sayer, John A., additional, Simms, Roslyn, additional, Sinha, Smeeta, additional, Srivastava, Shalabh, additional, Tam, Frederick W.K., additional, Thomas, Kay, additional, Turner, A. Neil, additional, Walsh, Stephen B., additional, Waters, Aoife, additional, Wilson, Patricia, additional, Wong, Edwin, additional, Abat, Sharirose, additional, Adalat, Shazia, additional, Agbonmwandolor, Joy, additional, Ahmad, Zubaidah, additional, Alejmi, Abdulfattah, additional, Almasarwah, Rashid, additional, Asgari, Ellie, additional, Ayers, Amanda, additional, Baharani, Jyoti, additional, Balasubramaniam, Gowrie, additional, Jo-Bamba Kpodo, Felix, additional, Bansal, Tarun, additional, Barratt, Alison, additional, Bates, Megan, additional, Bayne, Natalie, additional, Bendle, Janet, additional, Benyon, Sarah, additional, Bergmann, Carsten, additional, Bhandari, Sunil, additional, Boddana, Preetham, additional, Bond, Sally, additional, Bramham, Kate, additional, Branson, Angela, additional, Brearey, Stephen, additional, Brocklebank, Vicky, additional, Budwal, Sharanjit, additional, Byrne, Conor, additional, Cairns, Hugh, additional, Camilleri, Brian, additional, Campbell, Gary, additional, Capell, Alys, additional, Carmody, Margaret, additional, Carson, Marion, additional, Cathcart, Tracy, additional, Catley, Christine, additional, Cesar, Karine, additional, Chan, Melanie, additional, Chea, Houda, additional, Chess, James, additional, Cheung, Chee Kay, additional, Chick, Katy-Jane, additional, Chitalia, Nihil, additional, Christian, Martin, additional, Clark, Katherine, additional, Clayton, Christopher, additional, Clissold, Rhian, additional, Cockerill, Helen, additional, Coelho, Joshua, additional, Colby, Elizabeth, additional, Colclough, Viv, additional, Conway, Eileen, additional, Cook, H. Terence, additional, Cook, Wendy, additional, Cooper, Theresa, additional, Crosbie, Sarah, additional, Cserep, Gabor, additional, Date, Anjali, additional, Davidson, Katherine, additional, Davies, Amanda, additional, Dhaun, Neeraj, additional, Dhaygude, Ajay, additional, Diskin, Lynn, additional, Dixit, Abhijit, additional, Doctolero, Eunice Ann, additional, Dorey, Suzannah, additional, Downard, Lewis, additional, Drayson, Mark, additional, Dreyer, Gavin, additional, Dutt, Tina, additional, Etuk, Kufreabasi, additional, Evans, Dawn, additional, Finch, Jenny, additional, Flinter, Frances, additional, Fotheringham, James, additional, Francis, Lucy, additional, Gale, Daniel P., additional, Gallagher, Hugh, additional, Garcia, Eva Lozano, additional, Gavrila, Madita, additional, Gear, Susie, additional, Geddes, Colin, additional, Gilchrist, Mark, additional, Gittus, Matt, additional, Goggolidou, Paraskevi, additional, Goldsmith, Christopher, additional, Gooden, Patricia, additional, Goodlife, Andrea, additional, Goodwin, Priyanka, additional, Grammatikopoulos, Tassos, additional, Gray, Barry, additional, Griffith, Megan, additional, Gumus, Steph, additional, Gupta, Sanjana, additional, Hamilton, Patrick, additional, Harper, Lorraine, additional, Harris, Tess, additional, Haskell, Louise, additional, Hayward, Samantha, additional, Hegde, Shivaram, additional, Hendry, Bruce, additional, Hewins, Sue, additional, Hewitson, Nicola, additional, Hillman, Kate, additional, Hiremath, Mrityunjay, additional, Howson, Alexandra, additional, Htet, Zay, additional, Huish, Sharon, additional, Hull, Richard, additional, Humphries, Alister, additional, Hunt, David P.J., additional, Hunter, Karl, additional, Hunter, Samantha, additional, Ijeomah-Orji, Marilyn, additional, Inston, Nick, additional, Jayne, David, additional, Jenfa, Gbemisola, additional, Jenkins, Alison, additional, Jones, Caroline A., additional, Jones, Colin, additional, Jones, Amanda, additional, Jones, Rachel, additional, Kamesh, Lavanya, additional, Frankl, Fiona Karet, additional, Karim, Mahzuz, additional, Kaur, Amrit, additional, Kearley, Kelly, additional, Khwaja, Arif, additional, King, Garry, additional, King, Grant, additional, Kislowska, Ewa, additional, Klata, Edyta, additional, Kokocinska, Maria, additional, Lambie, Mark, additional, Lawless, Laura, additional, Ledson, Thomas, additional, Lennon, Rachel, additional, Levine, Adam P., additional, Maggie Lai, Ling Wai, additional, Lipkin, Graham, additional, Lovitt, Graham, additional, Lyons, Paul, additional, Mabillard, Holly, additional, Mackintosh, Katherine, additional, Mahdi, Khalid, additional, Maher, Eamonn, additional, Marchbank, Kevin J., additional, Mark, Patrick B., additional, Masunda, Bridgett, additional, Mavani, Zainab, additional, Mayfair, Jake, additional, McAdoo, Stephen, additional, Mckinnell, Joanna, additional, Melhem, Nabil, additional, Meyrick, Simon, additional, Morgan, Putnam, additional, Morgan, Ann, additional, Muhammad, Fawad, additional, Murray, Shona, additional, Novobritskaya, Kristina, additional, Ong, Albert CM., additional, Oni, Louise, additional, Osmaston, Kate, additional, Padmanabhan, Neal, additional, Parkes, Sharon, additional, Patrick, Jean, additional, Pattison, James, additional, Paul, Riny, additional, Percival, Rachel, additional, Perkins, Stephen J., additional, Persu, Alexandre, additional, Petchey, William G., additional, Pickering, Matthew C., additional, Pinney, Jennifer, additional, Plumb, Lucy, additional, Plummer, Zoe, additional, Popoola, Joyce, additional, Post, Frank, additional, Power, Albert, additional, Pratt, Guy, additional, Pusey, Charles, additional, Rabara, Ria, additional, Rabuya, May, additional, Raju, Tina, additional, Javier, Chadd, additional, Roberts, Ian SD., additional, Roufosse, Candice, additional, Rumjon, Adam, additional, Salama, Alan, additional, Saleem, Moin, additional, Sandford, R.N., additional, Sandu, Kanwaljit S., additional, Sarween, Nadia, additional, Sebire, Neil, additional, Selvaskandan, Haresh, additional, Shah, Sapna, additional, Sharma, Asheesh, additional, Sharples, Edward J., additional, Sheerin, Neil, additional, Shetty, Harish, additional, Shroff, Rukshana, additional, Sinha, Manish, additional, Smith, Kerry, additional, Smith, Lara, additional, Stott, Ian, additional, Stroud, Katerina, additional, Swift, Pauline, additional, Szklarzewicz, Justyna, additional, Tam, Fred, additional, Tan, Kay, additional, Taylor, Robert, additional, Tischkowitz, Marc, additional, Tse, Yincent, additional, Turnbull, Alison, additional, Turner, A Neil, additional, Tyerman, Kay, additional, Usher, Miranda, additional, Venkat-Raman, Gopalakrishnan, additional, Walker, Alycon, additional, Watt, Angela, additional, Webster, Phil, additional, Wechalekar, Ashutosh, additional, Welsh, Gavin Iain, additional, West, Nicol, additional, Wheeler, David, additional, Wiles, Kate, additional, Willcocks, Lisa, additional, Williams, Angharad, additional, Williams, Emma, additional, Williams, Karen, additional, Wilson, Deborah H., additional, Wilson, Patricia D., additional, Winyard, Paul, additional, Wong, Katie, additional, Wood, Grahame, additional, Woodward, Emma, additional, Woodward, Len, additional, Woolf, Adrian, additional, Wright, David, additional, Sy, Karla Therese L., additional, Huang, Kui, additional, Ye, Jamie, additional, Nitsch, Dorothea, additional, and Bockenhauer, Detlef, additional

Published
2024
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12. A unique subset of pericystic endothelium associates with aberrant microvascular remodelling and impaired blood perfusion early in polycystic kidney disease

Author

Jafree, Daniyal J, primary, Perera, Charith, additional, Ball, Mary, additional, Tolomeo, Daniele, additional, Pomeranz, Gideon, additional, Wilson, Laura, additional, Davis, Benjamin, additional, Mason, William J, additional, Funk, Eva Maria, additional, Kolatsi-Joannou, Maria, additional, Polschi, Radu, additional, Malik, Saif, additional, Stewart, Benjamin J, additional, Price, Karen L, additional, Mitchell, Hannah, additional, Motallebzadeh, Reza, additional, Muto, Yoshiharu, additional, Lees, Robert, additional, Needham, Sarah R, additional, Moulding, Dale, additional, Chandler, Jennifer C, additional, Walsh, Claire L, additional, Woolf, Adrian S, additional, Winyard, Paul JD, additional, Scambler, Peter J, additional, Hagerling, Rene, additional, Clatworthy, Menna R, additional, Humphreys, Benjamin, additional, Lythgoe, Mark F, additional, Walker-Samuel, Simon, additional, and Long, David A, additional

Published
2024
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14. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Author

Wong, Katie, primary, Pitcher, David, additional, Braddon, Fiona, additional, Downward, Lewis, additional, Steenkamp, Retha, additional, Annear, Nicholas, additional, Barratt, Jonathan, additional, Bingham, Coralie, additional, Chrysochou, Constantina, additional, Coward, Richard J, additional, Game, David, additional, Griffin, Sian, additional, Hall, Matt, additional, Johnson, Sally, additional, Kanigicherla, Durga, additional, Karet Frankl, Fiona, additional, Kavanagh, David, additional, Kerecuk, Larissa, additional, Maher, Eamonn R, additional, Moochhala, Shabbir, additional, Pinney, Jenny, additional, Sayer, John A, additional, Simms, Roslyn, additional, Sinha, Smeeta, additional, Srivastava, Shalabh, additional, Tam, Frederick W K, additional, Turner, Andrew Neil, additional, Walsh, Stephen B, additional, Waters, Aoife, additional, Wilson, Patricia, additional, Wong, Edwin, additional, Taylor, Christopher Mark, additional, Nitsch, Dorothea, additional, Saleem, Moin, additional, Bockenhauer, Detlef, additional, Bramham, Kate, additional, Gale, Daniel P, additional, Abat, Sharirose, additional, Adalat, Shazia, additional, Agbonmwandolor, Joy, additional, Ahmad, Zubaidah, additional, Alejmi, Abdulfattah, additional, Almasarwah, Rashid, additional, Asgari, Ellie, additional, Ayers, Amanda, additional, Baharani, Jyoti, additional, Balasubramaniam, Gowrie, additional, Kpodo, Felix, additional, Bansal, Tarun, additional, Barratt, Alison, additional, Bates, Megan, additional, Bayne, Natalie, additional, Bendle, Janet, additional, Benyon, Sarah, additional, Bergmann, Carsten, additional, Bhandari, Sunil, additional, Boddana, Preetham, additional, Bond, Sally, additional, Branson, Angela, additional, Brearey, Stephen, additional, Brocklebank, Vicky, additional, Budwal, Sharanjit, additional, Byrne, Conor, additional, Cairns, Hugh, additional, Camilleri, Brian, additional, Campbell, Gary, additional, Capell, Alys, additional, Carmody, Margaret, additional, Carson, Marion, additional, Cathcart, Tracy, additional, Catley, Christine, additional, Cesar, Karine, additional, Chan, Melanie, additional, Chea, Houda, additional, Chess, James, additional, Cheung, Chee Kay, additional, Chick, Katy-Jane, additional, Chitalia, Nihil, additional, Christian, Martin, additional, Chrysochou, Tina, additional, Clark, Katherine, additional, Clayton, Christopher, additional, Clissold, Rhian, additional, Cockerill, Helen, additional, Coelho, Joshua, additional, Colby, Elizabeth, additional, Colclough, Viv, additional, Conway, Eileen, additional, Cook, H Terence, additional, Cook, Wendy, additional, Cooper, Theresa, additional, Crosbie, Sarah, additional, Cserep, Gabor, additional, Date, Anjali, additional, Davidson, Katherine, additional, Davies, Amanda, additional, Dhaun, Neeraj, additional, Dhaygude, Ajay, additional, Diskin, Lynn, additional, Dixit, Abhijit, additional, Doctolero, Eunice, additional, Dorey, Suzannah, additional, Downard, Lewis, additional, Drayson, Mark, additional, Dreyer, Gavin, additional, Dutt, Tina, additional, Etuk, Kufreabasi, additional, Evans, Dawn, additional, Finch, Jenny, additional, Flinter, Frances, additional, Fotheringham, James, additional, Francis, Lucy, additional, Gallagher, Hugh, additional, Garcia, Eva, additional, Gavrila, Madita, additional, Gear, Susie, additional, Geddes, Colin, additional, Gilchrist, Mark, additional, Gittus, Matt, additional, Goggolidou, Paraskevi, additional, Goldsmith, Christopher, additional, Gooden, Patricia, additional, Goodlife, Andrea, additional, Goodwin, Priyanka, additional, Grammatikopoulos, Tassos, additional, Gray, Barry, additional, Griffith, Megan, additional, Gumus, Steph, additional, Gupta, Sanjana, additional, Hamilton, Patrick, additional, Harper, Lorraine, additional, Harris, Tess, additional, Haskell, Louise, additional, Hayward, Samantha, additional, Hegde, Shivaram, additional, Hendry, Bruce, additional, Hewins, Sue, additional, Hewitson, Nicola, additional, Hillman, Kate, additional, Hiremath, Mrityunjay, additional, Howson, Alexandra, additional, Htet, Zay, additional, Huish, Sharon, additional, Hull, Richard, additional, Humphries, Alister, additional, Hunt, David P J, additional, Hunter, Karl, additional, Hunter, Samantha, additional, Ijeomah-Orji, Marilyn, additional, Inston, Nick, additional, Jayne, David, additional, Jenfa, Gbemisola, additional, Jenkins, Alison, additional, Jones, Caroline A, additional, Jones, Colin, additional, Jones, Amanda, additional, Jones, Rachel, additional, Kamesh, Lavanya, additional, Karim, Mahzuz, additional, Kaur, Amrit, additional, Kearley, Kelly, additional, Khwaja, Arif, additional, King, Garry, additional, King, Grant, additional, Kislowska, Ewa, additional, Klata, Edyta, additional, Kokocinska, Maria, additional, Lambie, Mark, additional, Lawless, Laura, additional, Ledson, Thomas, additional, Lennon, Rachel, additional, Levine, Adam P, additional, Lai, Ling Wai Maggie, additional, Lipkin, Graham, additional, Lovitt, Graham, additional, Lyons, Paul, additional, Mabillard, Holly, additional, Mackintosh, Katherine, additional, Mahdi, Khalid, additional, Maher, Eamonn, additional, Marchbank, Kevin J, additional, Mark, Patrick B, additional, Masoud, Sherry, additional, Masunda, Bridgett, additional, Mavani, Zainab, additional, Mayfair, Jake, additional, McAdoo, Stephen, additional, Mckinnell, Joanna, additional, Melhem, Nabil, additional, Meyrick, Simon, additional, Morgan, Putnam, additional, Morgan, Ann, additional, Muhammad, Fawad, additional, Murray, Shona, additional, Novobritskaya, Kristina, additional, Ong, Albert CM, additional, Oni, Louise, additional, Osmaston, Kate, additional, Padmanabhan, Neal, additional, Parkes, Sharon, additional, Patrick, Jean, additional, Pattison, James, additional, Paul, Riny, additional, Percival, Rachel, additional, Perkins, Stephen J, additional, Persu, Alexandre, additional, Petchey, William G, additional, Pickering, Matthew C, additional, Pinney, Jennifer, additional, Plumb, Lucy, additional, Plummer, Zoe, additional, Popoola, Joyce, additional, Post, Frank, additional, Power, Albert, additional, Pratt, Guy, additional, Pusey, Charles, additional, Rabara, Ria, additional, Rabuya, May, additional, Raju, Tina, additional, Javier, Chadd, additional, Roberts, Ian S D, additional, Roufosse, Candice, additional, Rumjon, Adam, additional, Salama, Alan, additional, Sandford, Richard, additional, Sandu, Kanwaljit S, additional, Sarween, Nadia, additional, Sebire, Neil, additional, Selvaskandan, Haresh, additional, Sharma, Asheesh, additional, Sharples, Edward J, additional, Sheerin, Neil, additional, Shetty, Harish, additional, Shroff, Rukshana, additional, Sinha, Manish, additional, Smith, Kerry, additional, Smith, Lara, additional, Stott, Ian, additional, Stroud, Katerina, additional, Swift, Pauline, additional, Szklarzewicz, Justyna, additional, Tam, Fred, additional, Tan, Kay, additional, Taylor, Robert, additional, Tischkowitz, Marc, additional, Thomas, Kay, additional, Tse, Yincent, additional, Turnbull, Alison, additional, Turner, A Neil, additional, Tyerman, Kay, additional, Usher, Miranda, additional, Venkat-Raman, Gopalakrishnan, additional, Walker, Alycon, additional, Watt, Angela, additional, Webster, Phil, additional, Wechalekar, Ashutosh, additional, Welsh, Gavin I, additional, West, Nicol, additional, Wheeler, David, additional, Wiles, Kate, additional, Willcocks, Lisa, additional, Williams, Angharad, additional, Williams, Emma, additional, Williams, Karen, additional, Wilson, Deborah H, additional, Wilson, Patricia D, additional, Winyard, Paul, additional, Wong, Katie, additional, Wood, Grahame, additional, Woodward, Emma, additional, Woodward, Len, additional, Woolf, Adrian, additional, and Wright, David, additional

Published
2024
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15. CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases: A Genome-wide Association Study Among Patients with Obstructive Uropathies

Author

van der Zanden, Loes F.M., van Rooij, Iris A.L.M., Quaedackers, Josine S.L.T., Nijman, Rien J.M., Steffens, Martijn, de Wall, Liesbeth L.L., Bongers, Ernie M.H.F., Schaefer, Franz, Kirchner, Marietta, Behnisch, Rouven, Bayazit, Aysun K., Caliskan, Salim, Obrycki, Lukasz, Montini, Giovanni, Duzova, Ali, Wuttke, Matthias, Jennings, Rachel, Hanley, Neil A., Milmoe, Natalie J., Winyard, Paul J.D., Renkema, Kirsten Y., Schreuder, Michiel F., Roeleveld, Nel, and Feitz, Wout F.J.

Published
2021
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18. Detecting and monitoring incontinence associated dermatitis: Does impedance spectroscopy have a part to play?

Author

Owen, Emily J, Heylen, Rachel A, Stewart, Kyle, Winyard, Paul G, and Jenkins, A Toby A

Abstract

In this review, current understanding of the prevention and treatment of Incontinence Associated Dermatitis (IAD) is discussed. The need for preventative measures which target specific faecal/urinary irritants is highlighted, including the role of urease inhibitors. There is no existing internationally and clinically accepted method to diagnose and categorise the severity of IAD. Diagnosis currently relies on visual inspection; non-invasive techniques to assess skin barrier function could remove subjectiveness, particularly in darker skin tones. Impedance spectroscopy is a non-invasive technique which can be used to monitor skin barrier function, supporting visual assessments. Six studies (2003–2021) which used impedance to assess dermatitis were reviewed; inflamed skin was distinguishable from healthy skin in each case. This suggests that impedance spectroscopy could be useful in diagnosis early-stage IAD, potentially enabling earlier intervention. Finally, the authors present their initial findings on the role of urease in skin breakdown in an in vivo IAD model, using impedance spectroscopy. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Vascular Endothelial Growth Factor C for Polycystic Kidney Diseases

Author

Huang, Jennifer L, Woolf, Adrian S, Kolatsi-Joannou, Maria, Baluk, Peter, Sandford, Richard N, Peters, Dorien JM, McDonald, Donald M, Price, Karen L, Winyard, Paul JD, and Long, David A

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Kidney Disease, Polycystic Kidney Disease, Cardiovascular, Renal and urogenital, Animals, Mice, Polycystic Kidney Diseases, Vascular Endothelial Growth Factor C, endothelium, polycystic kidney disease, vascular endothelial growth factor, Clinical Sciences, Urology & Nephrology, Clinical sciences
Abstract

Polycystic kidney diseases (PKD) are genetic disorders characterized by progressive epithelial cyst growth leading to destruction of normally functioning renal tissue. Current therapies have focused on the cyst epithelium, and little is known about how the blood and lymphatic microvasculature modulates cystogenesis. Hypomorphic Pkd1(nl/nl) mice were examined, showing that cystogenesis was associated with a disorganized pericystic network of vessels expressing platelet/endothelial cell adhesion molecule 1 and vascular endothelial growth factor receptor 3 (VEGFR3). The major ligand for VEGFR3 is VEGFC, and there were lower levels of Vegfc mRNA within the kidneys during the early stages of cystogenesis in 7-day-old Pkd1(nl/nl) mice. Seven-day-old mice were treated with exogenous VEGFC for 2 weeks on the premise that this would remodel both the VEGFR3(+) pericystic vascular network and larger renal lymphatics that may also affect the severity of PKD. Treatment with VEGFC enhanced VEGFR3 phosphorylation in the kidney, normalized the pattern of the pericystic network of vessels, and widened the large lymphatics in Pkd1(nl/nl) mice. These effects were associated with significant reductions in cystic disease, BUN and serum creatinine levels. Furthermore, VEGFC administration reduced M2 macrophage pericystic infiltrate, which has been implicated in the progression of PKD. VEGFC administration also improved cystic disease in Cys1(cpk/cpk) mice, a model of autosomal recessive PKD, leading to a modest but significant increase in lifespan. Overall, this study highlights VEGFC as a potential new treatment for some aspects of PKD, with the possibility for synergy with current epithelially targeted approaches.

Published
2016

24. Cellular Pre-Adaptation to the High O 2 Concentration Used in Standard Cell Culture Confers Resistance to Subsequent H 2 O 2 -Induced Cell Death.

Author

Jordan, Jack B., Smallwood, Miranda J., Smerdon, Gary R., and Winyard, Paul G.

Subjects
CELL death, APOPTOSIS, CELL culture, GLUTATHIONE reductase, SQUAMOUS cell carcinoma, HYDROGEN peroxide
Abstract

The addition of hydrogen peroxide (H2O2) to cultured cells is widely used as a method to modulate redox-regulated cellular pathways, including the induction of programmed cell death in cell culture experiments and the testing of pro- and antioxidant compounds. Here, we assessed the effect on the cellular response to H2O2 of pre-adapting squamous cell carcinoma cells (A431) to the standard cell culture oxygenation of 18.6% O2, compared to cells pre-adapted to a physiological skin O2 concentration (3.0% O2). We showed that cells pre-adapted to 18.6% O2 resisted H2O2-induced cell death compared to cells pre-adapted to 3.0% O2 for 96 h prior to treatment with H2O2. Moreover, the enzymatic activities of catalase and glutathione reductase, as well as the protein expression levels of catalase, were higher in cells pre-adapted to 18.6% O2 compared to cells pre-adapted to 3.0% O2. H2O2-resistant cells, pre-adapted to 18.6% O2, exhibited increased nuclear Nrf-2 levels. It is concluded that A431 cells pre-adapted to standard cell culture oxygenation conditions resist H2O2-induced cell death. This effect may be related to their heightened activation of Nrf-2. [ABSTRACT FROM AUTHOR]

Published
2024
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27. A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces the Activation of Intrinsic Apoptosis via Subcellular Ultrastructural and Ca2+ Efflux Alterations in an In Vitro Model of Human Malignant Melanoma

Author

Kyriakou, Sotiris, primary, Potamiti, Louiza, additional, Demosthenous, Nikoletta, additional, Amery, Tom, additional, Stewart, Kyle, additional, Winyard, Paul G., additional, Franco, Rodrigo, additional, Pappa, Aglaia, additional, and Panayiotidis, Mihalis I., additional

Published
2023
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30. List of Contributors

Author

Acharya, Ganesh, primary, Aertsen, Michael, additional, Afshar, Yalda, additional, Ananth, Cande V., additional, Ashworth, Michael, additional, Au, Patrick, additional, Bakalis, Spyros, additional, Benoist, Guillaume, additional, Bilancia, Colleen G., additional, Bilardo, Caterina M., additional, Bryant, Louise D., additional, Butler, Colin R., additional, Van Calenbergh, Frank, additional, Caritis, Steve N., additional, Chitty, Lyn S., additional, Collins, Patricia, additional, Cook, James, additional, Cuckle, Howard, additional, David, Anna L., additional, De Catte, Luc, additional, De Coppi, Paolo, additional, de Jong-Pleij, Elisabeth, additional, De Keersmaecker, Bart, additional, Deprest, Jan, additional, Devlieger, Roland, additional, de Wert, Guido M., additional, Dickinson, Jan E., additional, Dilworth, Mark, additional, Dondorp, Wybo J., additional, Dunk, Caroline E., additional, Everett, Thomas R., additional, Fisher, Jane, additional, Galan, Henry L., additional, Ganapathi, Mythily, additional, Gardiner, Helena M., additional, Gotherstrom, Cecilia, additional, Harding, Richard, additional, Hewison, Jenny, additional, Hewitt, Richard J., additional, Hiersch, Liran, additional, Hill, Melissa, additional, Hillman, Sara L., additional, Hindryckx, An, additional, Hooper, Stuart B., additional, Huppertz, Berthold, additional, Hutchinson, J. Ciaran, additional, Hyett, Jon, additional, Joyeux, Luc, additional, Jurkovic, Davor, additional, Kingdom, John C., additional, Langlois, Sylvie, additional, Lemon, Lara S., additional, Leruez-Ville, Marianne, additional, Lewi, Liesbeth, additional, Levy, Brynn, additional, Loke, Y.W., additional, Lopriore, Enrico, additional, Macones, George A., additional, Malone, Fergal D., additional, Martirosian, Anahit, additional, McAuliffe, Fionnuala, additional, McDougall, Annie R.A., additional, Moise, Kenneth J., additional, Moffett, Ashley, additional, Müllers, Sieglinde M., additional, Neiger, Ran, additional, Newnham, John P., additional, Obican, Sarah G., additional, Odibo, Anthony O., additional, Oepkes, Dick, additional, Pandya, Pranav P., additional, Platt, Lawrence D., additional, Pratt, Rosalind, additional, Rajah, Kuhan, additional, Rao, Rashmi, additional, Richter, Jute, additional, Rosenbloom, Joshua I., additional, Russo, Francesca Maria, additional, Scialli, Anthony R., additional, Sebire, Neil J., additional, Sharkey, Andrew, additional, Shelmerdine, Susan C., additional, Sibley, Colin, additional, Snowise, Saul, additional, Steggerda, Sylke, additional, Su, Emily J., additional, Tang, Mary, additional, Te Pas, Arjan B., additional, Tita, Alan T., additional, Ushakov, Fred, additional, Van den Veyver, Ignatia B., additional, van Klink, Jeanine M., additional, Venkataramanan, Raman, additional, Ville, Yves, additional, Walkiewicz, Magdalena, additional, Wallis, Colin, additional, Walther-Jallow, Lilian, additional, Wapner, Ronald J., additional, Westgren, Magnus, additional, White, Scott W., additional, Wilson, Louise C., additional, Wilson, R. Douglas, additional, Winkelhorst, Dian, additional, Winyard, Paul J.D., additional, Wohlmuth, Christoph, additional, Wou, Karen, additional, Yaron, Yuval, additional, Leung, Kwok Yin, additional, and Yulia, Angela, additional

Published
2020
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36. Central blood pressure and measures of early vascular disease in children with ADPKD

Author

Marlais, Matko, Rajalingam, Sreedevi, Gu, Haotian, Savis, Alexandra, Sinha, Manish D, and Winyard, Paul JD

Subjects
Blood pressure -- Control, Children -- Health aspects, Blood circulation disorders -- Diagnosis, Health
Abstract

Background There is growing recognition of hypertension in a significant proportion of children with ADPKD. In this study, we assessed blood pressure and cardiovascular status in children with ADPKD. Methods A prospective two-centre observational study of children (< 18 years) with ADPKD was compared against age- and BMI-matched healthy controls. Children underwent peripheral BP (pBP) measured using an aneroid sphygmomanometer and auscultation, 24-h ambulatory BP monitoring (ABPM), non-invasive central BP (cBP) measurement, carotid-femoral pulse wave velocity (PWVcf) measured using applanation tonometry and measurement of indexed left ventricular mass (LVMI) using echocardiography. This study received independent ethical approval. Results Forty-seven children with ADPKD and 49 healthy controls were recruited (median age 11 years vs. 12 years). Children with ADPKD had significantly higher systolic pBP (mean 112 ± 13.5 mmHg vs. 104 ± 11 mmHg, p < 0.001), higher systolic cBP (mean 97 ± 12.8 mmHg vs. 87 ± 9.8 mmHg, p < 0.001) and lower pulse pressure amplification ratio (1.59 ± 0.2 vs. 1.67 ± 0.1, p = 0.04) compared to healthy children. Thirty-five percent of children with ADPKD showed a lack of appropriate nocturnal dipping on 24-h ABPM. There was no difference in PWVcf between children with ADPKD and healthy children (mean 5.74 ± 1 m/s vs. 5.57 ± 0.9 m/s, p = 0.46). Those with ADPKD had a significantly higher LVMI (mean 30.4 ± 6.6 g/m.sup.2.7 vs. 26.2 ± 6.2 g/m.sup.2.7, p = 0.01). Conclusions These data highlight the high prevalence of hypertension in children with ADPKD, also demonstrating early cardiovascular dysfunction with increased LVMI and reduced PP amplification despite preserved PWVcf, when compared with healthy peers. These early cardiovascular abnormalities are likely to be amenable to antihypertensive therapy, reinforcing the need for routine screening of children with ADPKD., Author(s): Matko Marlais [sup.1] [sup.2] , Sreedevi Rajalingam [sup.2] , Haotian Gu [sup.2] , Alexandra Savis [sup.3] , Manish D Sinha [sup.2] [sup.4] , Paul JD Winyard [sup.1] Author Affiliations: [...]

Published
2019
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37. International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

Author

Gimpel, Charlotte, Bergmann, Carsten, Bockenhauer, Detlef, Breysem, Luc, Cadnapaphornchai, Melissa A., Cetiner, Metin, Dudley, Jan, Emma, Francesco, Konrad, Martin, Harris, Tess, Harris, Peter C., König, Jens, Liebau, Max C., Marlais, Matko, Mekahli, Djalila, Metcalfe, Alison M., Oh, Jun, Perrone, Ronald D., Sinha, Manish D., Titieni, Andrea, Torra, Roser, Weber, Stefanie, Winyard, Paul J. D., and Schaefer, Franz

Published
2019
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38. Some Personal Conclusions

Author

Jacob, Claus, Burkholz, Torsten, Kirsch, Gilbert, Slusarenko, Alan, Winyard, Paul G., Jacob, Claus, editor, Kirsch, Gilbert, editor, Slusarenko, Alan, editor, Winyard, Paul G., editor, and Burkholz, Torsten, editor

Published
2014
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39. Introduction

Author

Jacob, Claus, Burkholz, Torsten, Kirsch, Gilbert, Slusarenko, Alan, Winyard, Paul G., Jacob, Claus, editor, Kirsch, Gilbert, editor, Slusarenko, Alan, editor, Winyard, Paul G., editor, and Burkholz, Torsten, editor

Published
2014
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44. Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.

Author

L'Heureux, Joanna E., van der Giezen, Mark, Winyard, Paul G., Jones, Andrew M., and Vanhatalo, Anni

Subjects
MICROBIAL communities, DENITRIFYING bacteria, NEISSERIA, BACTERIAL diversity, MICROBACTERIUM, HUMAN microbiota, CORYNEBACTERIUM
Abstract

The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health. [ABSTRACT FROM AUTHOR]

Published
2023
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46. The biology of kidney malformations

Author

Winyard, Paul Julian Douglas

Subjects
572.8, Chronic renal failure, Cell biology
Abstract

Kidney malformations, such as dysplastic kidneys, are the commonest cause of chronic renal failure in infants and young children. It has been suggested, based on anatomical descriptions, that failure of ureteric bud branching and mesenchymal induction leads to dysplasia, yet little is known about the underlying molecular mechanisms. In this thesis, therefore, I have examined several aspects of the cell biology of human dysplastic kidneys, and compared them with normal developing and mature kidneys. In normal developing kidneys, proliferation was prominent in the nephrogenic cortex whilst apoptosis was predominantly detected in early nephron precursors and in the medulla. The transcription factor PAX-2 was expressed in actively proliferating cells in both ureteric bud ampullae and condensing mesenchyme. In contrast, the transcription factor WT-1 and survival factor BCL-2 were solely detected in the condensing mesenchyme and developing nephrons, whilst the cell adhesion molecule galectin-3 was restricted to the ureteric bud lineage. In the mature kidney PAX-2 and BCL-2 were downregulated, whilst WT-1 expression persisted in podocytes and galectin-3 was detected in a-intercalated cells of collecting ducts. In dysplastic kidneys, proliferation was prominent in dysplastic tubules and cysts, and PAX-2, BCL-2 and galectin-3 were persistently expressed in these epithelia. Therefore, continuous proliferation signals in combination with ectopic survival factors may explain cyst formation in these 'immature' dysplastic epithelia. In contrast, apoptosis was prominent in cells in the surrounding loosely arranged 'mesenchymal' tissue. These cells expressed WT-1, but did not express PAX-2 and BCL-2 and these factors may therefore be essential for precursor survival and proliferation during nephron formation. In addition, in preliminary experiments, cells were cultured from dysplastic kidneys and transduced with a simian virus 40 (SV40) large T antigen construct. In future, culture and characterisation of these potentially immortal cells may provide a novel method to investigate the functional biology of kidney malformations.

Published
1998

47. Clinical presentation of childhood soft tissue sarcomas: a systematic review and meta-analysis

Author

Ni Cheallaigh, Lorna, Liu, Jo-Fen, Fern, Lorna, Winyard, Paul, Walker, David, Ball-Gamble, Ashley, and Shanmugavadivel, Dhurgshaarna

Abstract

BackgroundTime to diagnosis (TTD) of childhood soft tissue sarcoma (STS) is significantly associated with survival. This review aims to identify pre-diagnostic symptoms/signs to inform earlier diagnosis interventions.MethodsMedline, Embase, Cochrane and Web-of-Science were searched between January 2010 and February 2021 for studies including children (<18 years) diagnosed with STS, with no language restrictions. Pooled proportions of symptoms/signs were calculated and subanalysed by tumour location and age.ResultsFifty-nine eligible studies were identified, totalling 2462 cases. The most frequent symptoms were lump/swelling (38%, 95% CI 27% to 51%), pain (6%, 95% CI 3% to 10%), cutaneous changes (4%, 95% CI 0 to 9%), localised eye swelling (3%, 95% CI 0 to 7%), cranial nerve deficits (2%, 95% CI 0 to 5%) and constitutional symptoms (2%, 95% CI 0 to 5%).Symptoms varied by location and age. Localised eye swelling (20%, 95% CI 3% to 45%), cranial nerve deficits (14%, 95% CI 4% to 28%) and impaired visual function (6%, 95% CI 0 to 17%) were frequent in head and neck tumours. For abdomen/pelvic tumours, urinary symptoms (24%, 95% CI 5% to 15%), abdominal distension/discomfort (22%, 95% CI 4% to 47%), genital lump/swelling (16%, 95% CI 1% to 42%), constitutional symptoms (9%, 95% CI 0%] to 23%), vaginal bleeding (7%, 95%C I 0 to 21%) and bowel habit changes (6%, 95% CI 0 to 17%) were frequent.In <5 years, consumptive coagulopathy (16%, 95% CI 0 to 48%), cutaneous changes (5%, 95% CI 0 to 40%), genital lump/swelling (4%, 95% CI 0 to 14%), reduced mobility (3%, 95% CI 0 to 11%), vaginal bleeding (2%, 95% CI 0 to 11%) and bleeding/bruising/petechiae (2%, 95% CI 0 to 20%) were frequent compared with lump/swelling, constitutional symptoms, pain and headaches which were frequent among >11 years.ConclusionsFor STS, pre-diagnostic symptoms differ by age and location, highlighting the need to tailor early diagnosis interventions.

Published
2024
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50. A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces the Activation of Intrinsic Apoptosis via Subcellular Ultrastructural and Ca 2+ Efflux Alterations in an In Vitro Model of Human Malignant Melanoma.

Author

Kyriakou, Sotiris, Potamiti, Louiza, Demosthenous, Nikoletta, Amery, Tom, Stewart, Kyle, Winyard, Paul G., Franco, Rodrigo, Pappa, Aglaia, and Panayiotidis, Mihalis I.

Abstract

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and -9. Among all extract fractions, the phenethyl isothiocyanate-enriched one (PhEF) possessed significant cytotoxicity against A375 and COLO-679 cells, while HaCaT cells remained relatively resistant at sub-lethal and lethal concentrations. Additionally, ultrastructural subcellular alterations associated with apoptosis were observed by means of increased mitochondrial area and perimeter, decreased cristae density and a shorter distance of the endoplasmic reticulum to the mitochondria, all taking place during "early" time points (2–4 h) of exposure. Moreover, PhEF induced mitochondrial membrane depolarization associated with "late" time points (24 h) of exposure, thereby leading to the activation of intrinsic apoptosis. Finally, the inhibition of cytosolic Ca2+ efflux reduced levels of caspases-9 and -3 activity, suggesting the involvement of Ca2+ efflux in modulating the activation of intrinsic apoptosis. To conclude, our data demonstrate an association of "early" ultrastructural alterations in mitochondria and the endoplasmic reticulum with the "late" induction of intrinsic apoptosis via the modulation of Ca2+ efflux. [ABSTRACT FROM AUTHOR]

Published
2023
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