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E T Spear, E A Holt, E J Joyce, M M Haag, S M Mawe, G W Hennig, B Lavoie, A M Applebee, C Teuscher, G M Mawe
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that, in addition to motor, sensory, and cognitive symptoms, also causes constipation, which is poorly understood. Here, we characterize gastrointestinal (GI) dysmotility in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS and evaluate whether autoantibodies target the enteric nervous system (ENS) and cause dysmotility. METHODS: EAE was induced in male SJL and B6 mice...
April 11, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
James Miles, Christopher J Applebee, Pierre Leboucher, Sonia Lopez-Fernandez, Dae-Jin Lee, Rosa Guarch, Stephen Ward, Peter J Parker, Jose I López, Banafshé Larijani
Purpose: Clear cell Renal Cell Carcinomas (ccRCC), the largest group of renal tumours, are resistant to classical therapies. The determination of the functional state of actionable biomarkers for the assessment of these adenocarcinomas is essential. The dysregulation of the oncoprotein, PKB/Akt has been linked with poor prognoses in human cancers. Material & methods: We analysed the status of the PKB/Akt pathway in a representative tumour tissue microarray obtained from the primary tumours and their metastases in 60 ccRCC with long term follow up...
December 2017: BBA Clinical
Andrew J Solomon, Dennis N Bourdette, Anne H Cross, Angela Applebee, Philip M Skidd, Diantha B Howard, Rebecca I Spain, Michelle H Cameron, Edward Kim, Michele K Mass, Vijayshree Yadav, Ruth H Whitham, Erin E Longbrake, Robert T Naismith, Gregory F Wu, Becky J Parks, Dean M Wingerchuk, Brian L Rabin, Michel Toledano, W Oliver Tobin, Orhun H Kantarci, Jonathan L Carter, B Mark Keegan, Brian G Weinshenker
OBJECTIVE: To characterize patients misdiagnosed with multiple sclerosis (MS). METHODS: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. RESULTS: Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%)...
September 27, 2016: Neurology
Gail F Davies, Beth J Greenhough, Pru Hobson-West, Robert G W Kirk, Ken Applebee, Laura C Bellingan, Manuel Berdoy, Henry Buller, Helen J Cassaday, Keith Davies, Daniela Diefenbacher, Tone Druglitrø, Maria Paula Escobar, Carrie Friese, Kathrin Herrmann, Amy Hinterberger, Wendy J Jarrett, Kimberley Jayne, Adam M Johnson, Elizabeth R Johnson, Timm Konold, Matthew C Leach, Sabina Leonelli, David I Lewis, Elliot J Lilley, Emma R Longridge, Carmen M McLeod, Mara Miele, Nicole C Nelson, Elisabeth H Ormandy, Helen Pallett, Lonneke Poort, Pandora Pound, Edmund Ramsden, Emma Roe, Helen Scalway, Astrid Schrader, Chris J Scotton, Cheryl L Scudamore, Jane A Smith, Lucy Whitfield, Sarah Wolfensohn
Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways...
2016: PloS One
M-Alain Babi, Angela Applebee, Robert Shapiro, Waqar Waheed
Background The syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a self-limited benign disorder of unclear pathogenesis, with diverse clinical manifestations. Cases We report two unusual presentations of this entity. The first case developed a catastrophic picture, characterized by acute elevation of intracranial pressure, necessitating emergency life support. The second case presented with hyperacute-onset mixed aphasia and facial droop, masquerading as acute ischemia of the middle cerebral artery territory...
March 2017: Cephalalgia: An International Journal of Headache
Angela Applebee, Andrew D Goodman, Angeli S Mayadev, Francois Bethoux, Myla D Goldman, Michael Klingler, Andrew R Blight, Enrique J Carrazana
PURPOSE: Dalfampridine extended-release (ER) tablets 10 mg BID have been approved for use in improving walking in people with multiple sclerosis (MS). This subgroup analysis evaluated the effects of dalfampridine ER 5 and 10 mg BID on distance walked, as assessed using the 6-minute walk (6MW) test. METHODS: This analysis of data from a randomized, placebo-controlled, double-blind study (N = 430) included only the 153 patients with 6MW data available. Participants (aged 18-70 years) were randomly assigned in a 1:1:1 ratio to receive dalfampridine ER 5 or 10 mg or placebo, BID for 4 weeks...
December 1, 2015: Clinical Therapeutics
Aili Wang, Li Liu, Yanchun Peng, Shahidul Islam, Marie Applebee, Rudi Appels, Yueming Yan, Wujun Ma
Low molecular weight glutenin subunits (LMW-GS) play an important role in determining dough properties and breadmaking quality. However, resolution of the currently used methodologies for analyzing LMW-GS is rather low which prevents an efficient use of genetic variations associated with these alleles in wheat breeding. The aim of the current study is to evaluate and develop a rapid, simple, and accurate method to differentiate LMW-GS alleles using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry...
2015: PloS One
Robert Yapundich, Angela Applebee, Francois Bethoux, Myla D Goldman, George J Hutton, Michele Mass, Gabriel Pardo, Michael Klingler, Herbert R Henney, Andrew R Blight, Enrique J Carrazana
BACKGROUND: Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg. METHODS: Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose...
May 2015: International Journal of MS Care
Jay V Gonyea, Richard Watts, Angela Applebee, Trevor Andrews, Scott Hipko, Joshua P Nickerson, Lindsay Thornton, Christopher G Filippi
BACKGROUND: To apply quantitative whole-brain T1 -rho (T1ρ ) and T2 imaging to the detection and quantification of brain changes resulting from multiple sclerosis (MS). METHODS: Twenty-three MS patients with clinically isolated syndrome (10) and relapsing remitting MS (13) phenotypes, compared with 24 age-matched healthy controls were imaged at 3 Tesla. An axial T1ρ -weighted three-dimensional turbo spin echo sequence with a variable flip angle and fluid suppression was used...
December 2015: Journal of Magnetic Resonance Imaging: JMRI
Richard D Byrne, Selvaraju Veeriah, Christopher J Applebee, Banafshé Larijani
The fusogenic lipid diacylglycerol is essential for remodeling gamete and zygote nuclear envelopes (NE) during early embryogenesis. It is unclear whether upstream signaling molecules are likewise conserved. Here we demonstrate PLCγ and its activator SFK1, which co-operate during male pronuclear envelope formation, also promote the subsequent male and female pronuclear fusion. PLCγ and SFK1 interact directly at the fusion site leading to PLCγ activation. This is accompanied by a spatially restricted reduction of PtdIns(4,5)P2...
September 2014: Nucleus
Mohamed-Ali Babi, Todd Raleigh, Robert E Shapiro, Joseph McSherry, Angela Applebee
No abstract text is available yet for this article.
October 14, 2014: Neurology
Richard D Byrne, Selvaraju Veeriah, Christopher J Applebee, Banafshé Larijani
The fusogenic lipid diacylglycerol is essential for remodeling gamete and zygote nuclear envelopes (NE) during early embryogenesis. It is unclear whether upstream signaling molecules are likewise conserved. Here we demonstrate PLCγ and its activator SFK1, which co-operate during male pronuclear envelope formation, also promote the subsequent male and female pronuclear fusion. PLCγ and SFK1 interact directly at the fusion site leading to PLCγ activation. This is accompanied by a spatially restricted reduction of PtdIns(4,5)P 2...
August 11, 2014: Nucleus
Hrayr Attarian, Garrick Applebee, Angela Applebee, Bingxia Wang, Melissa Clark, Becky McCormick, Emma Salzman, Catherine Schuman
The prevalence of moderate-to-severe sleep problems is significantly higher among people with multiple sclerosis (MS) than in the general population. In 2002, we found a significant relationship between fatigue and disrupted sleep in patients with relapsing-remitting MS (RRMS). The objectives of this study were to determine whether eszopiclone (Lunesta; Sunovion Pharmaceuticals Inc, Marlborough, MA) was superior to placebo in improving sleep among patients with MS-related fatigue and sleep complaints (primary end point); and to assess the impact of improved sleep on daytime fatigue and functioning (secondary end point)...
2011: International Journal of MS Care
Oana Dumitrascu, Carlos H Schenck, Garrick Applebee, Hrayr Attarian
BACKGROUND: Parasomnia overlap disorder (POD) currently is classified by the International Classification of Sleep Disorders, Second Edition (ICSD-2) as a variant of rapid eye movement (REM) sleep behavior disorder (RBD), and therefore its diagnosis also implies counseling the patients on the increased risk for developing neurodegenerative disorders. POD pathophysiology is not clear to date. METHODS: The authors report 5 cases of POD, review the literature, and analyze previously published cases of POD...
November 2013: Sleep Medicine
Jacky Davis, Ian Banks, David Wrigley, Clive Peedell, Alyson Pollock, Klim McPherson, Martin McKee, William L Irving, Peter Crome, Trisha Greenhalgh, Walter Holland, David Evans, Alan Maryon-Davis, Alan Smyth, Peter Fleming, Michel Coleman, Deborah J Sharp, Peter Whincup, Stuart Logan, Derek Cook, Robert Moore, Salman Rawaf, J McEewen, Robert West, John S Yudkin, Aileen Clarke, Nick Finer, Paola Domizio, Clare Bambra, Anna Jones, Gene Feder, Alex Scott-Samuel, Louise Irvine, Ajay Sharma, Mike Fitchett, Kambiz Boomla, Jonathan Folb, Ashish Paul, David McCoy, Ray Tallis, Jilla Burgess-Allen, Mark Edwards, Jonathon Tomlinson, Deborah Colvin, Jonathan Gore, Kirsten Brown, Sarah Mitchel, Alice Lau, Mel Sayer, Leon Clark, Ruth Silverman, Saul Marmot, Daniel Rainbow, Lucy Carter, Nick Mann, Richard Fielding, Jane Logan, Louise Tebboth, Natasha Arnold, Kate Stobbart, Kate Cabot, Sarah Finer, Martin Edwards, David Davies, Helen Buttivant, Sebastian Kraemer, Jo Newell, Alun Griffiths, Richard Fitzgerald, Robert Macgibbon, Alan Lee, A F Macklon, Esther Hobson, David Jenner, Bobbie Jacobson, Alison Timmis, Asad Salim, John Evans-Jones, Woody Caan, Ninaad Awsare, Neil Pride, Ruth Suckling, Catherine Bratty, Brian Rossiter, David Hawkins, Jonny Currie, Corinne Camilleri-Ferrante, Jonathan Fluxman, Osman Bhatti, James Anson, Robert Etherington, David Lawrence, Henry Fell, Edward Clarke, Julian Ormerod, Oliver Ormerod, Maggie Ireland, John A T Duncan, Rajiv Chandy, Jennifer Mindell, Paul Mullen, Phillip Bennett-Richards, Julie Hirst, E Murphy, P Martin, Simon Lowes, Peter Fleming, Richard Grunewald, Joanne Reeve, Martin Schweiger, Jonathan Coates, George Farrelly, M A Chamberlain, Geoffrey Lewis, Jane Young, Brian Scott, John Gibbs, Aileen Landers, Pete Deveson, Grant Ingrams, Martha Leigh, Jeff Gawler, Amy Ford, Jonathan Nixon, Margaret McCartney, David Bareford, Surinder Singh, Kate Lockwood, Michael Cripwell, Peter Ehrhardt, David Bell, Pam Wortley, Laurie Tomlinson, Julie Hotchkiss, Steven Ford, Gill Turner, Gerard Reissman, David Lewis, Chris Johnstone, Mike Tomson, Payam Torabi, David Bell, D Tomson, Alex Tulloch, Sally Johnston, Jane Dickinson, Elisabeth McElderry, Wendy Ross, Kim Holt, Mary Logan, Hilary Klonin, David Jenner, Jude Danby, V Goodger, John Puntis, Harriet Dickson, Derek A Gould, Anna Livingstone, Dianne Lefevre, Bryony Kendall, G Singh, Peter Hall, Jonathan Darling, Adrian N Hamlyn, Anita Patel, Jonathan Erskine, Brian Fisher, Richard Hughes, Clare Highton, Helen Venning, Ron Singer, Steve Brearey, Jim Sikorski, David Paintin, John Feehally, Wendy Savage, Kathy McAdam Freud, Victoria J Holt, Alison Gill, Tony Waterston, Richard de Souza, Nicholas Hopkinson, Mike Beadsworth, Andrea Franks, Helen Daley, Paul Cullinan, Adriana Basarab, Jonathan Folb, Hugh Gurling, Pam Zinkin, Simon Kirwin, Ernst Buhrs, Raymond Brown, Andrew West, Gary Marlowe, Griffith Fellows, John Main, Jackie Applebee, M Koperski, Phil Jones, Alison Macfarlane, Naomi Beer, Rebecca Mason, Robert West, Maggie Eisner, Alison Smailes, Philip Timms, David Knight, Coral Jones, Barbara Wesby, Laura Lyttelton, Richard Morrison, David Bossano, Jonathan Walker, Gerry Davies, Peter Godfrey, Ingrid Wolfe, Emmanuel Nsutebu, Nicola Stevenson, Sheila Cheeroth, Jo Miller, Guy Johnson, R Noor, Alyson Hall, David Bostock, Benedict Michael, John Sharvill, Jamie Macpherson, David Lewis, Richard Ma, John Middleton, Anne Jeffreys, Jim Cole, John P Boswell, Bob Bury, Sally Mitchison, Ann-Louise Kinmonth, Gail Young, Iain Maclennan, Pat Munday
No abstract text is available yet for this article.
March 20, 2013: BMJ: British Medical Journal
Angela Applebee
Multiple sclerosis (MS) and migraine headache coexist in many young female patients. Whether this is coincidental or causally linked remains unclear. The presenting symptoms and signs of MS relapse and migraine aura can be similar and should be differentiated by careful history and examination to ensure proper diagnosis and treatment. White matter lesions on magnetic resonance imaging have specific patterns for each entity and also need to be interpreted carefully. Although a clear link has not been established between migraine and MS, numerous studies have been reported assessing risks, prevalence, and causation...
October 2012: Headache
Richard D Byrne, Christopher Applebee, Dominic L Poccia, Banafshé Larijani
The nuclear envelope (NE) breaks down and reforms during each mitotic cycle. A similar process happens to the sperm NE following fertilisation. The formation of the NE in both these circumstances involves endoplasmic reticulum membranes enveloping the chromatin, but PLCγ-dependent membrane fusion events are also essential. Here we demonstrate the activation of PLCγ by a Src family kinase (SFK1) during NE assembly. We show by time-resolved FRET for the first time the direct in vivo interaction and temporal regulation of PLCγ and SFK1 in sea urchins...
2012: PloS One
Hillel Panitch, Angela Applebee
INTRODUCTION: Walking impairment is a clinical hallmark of multiple sclerosis (MS), a chronic neurologic disease characterized by axonal demyelination and dysfunction that results in progressive disability. Until recently, there were no therapies that specifically targeted the axonal dysfunction associated with walking impairment in MS. AREAS COVERED: The purpose of this review is to discuss the unmet need for the treatment of walking impairment in MS patients and to evaluate how a new class of pharmacologic therapies, neurofunctional modifiers, potentially addresses this unmet need...
July 2011: Expert Opinion on Pharmacotherapy
M Kenyon Applebee, Andrew R Joyce, Tom M Conrad, Donald W Pettigrew, Bernhard Ø Palsson
Herein we measure the effect of four adaptive non-synonymous mutations to the glycerol kinase (glpK) gene on catalytic function and regulation, to identify changes that correlate to increased fitness in glycerol media. The mutations significantly reduce affinity for the allosteric inhibitor fructose-1,6-bisphosphate (FBP) and formation of the tetramer, which are structurally related, in a manner that correlates inversely with imparted fitness during growth on glycerol, which strongly suggests that these enzymatic parameters drive growth improvement...
July 1, 2011: Journal of Biological Chemistry
Mario A Monteiro, Stacey Britton, Lisa A Applebee, Shahida Baqar
Helicobacter pylori infection in humans is responsible for the onset of severe gastric disorders and a vaccine would be an improvement over current antibiotic-based treatments. Lipopolysaccharide (LPS; O-chain PS→core→lipid A) is a main H. pylori cell wall component, whose O-chain PS exhibits molecular mimicry and therefore any LPS-based vaccine cannot contain O-chain epitopes. Here, the conjugation of de-lipidated H. pylori O:2 LPS to BSA and its immunogenicity in mice is described. IgG antibodies were observed to recognize the LPSs of representative H...
April 12, 2011: Vaccine
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