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Doug Murphy

Doug N Halligan, Stephen J E Murphy, Cormac T Taylor
Crosstalk between metabolic and immune pathways has recently become appreciated to be key to the regulation of host defence. The hypoxia-inducible factor (HIF) is a transcription factor which was initially described as a ubiquitous master regulator of the transcriptional response to hypoxia. In this role, HIF regulates genes promoting adaptation to hypoxia including a number which influence the cellular metabolic strategy of a cell. It has more recently been appreciated that the regulation of HIF is not restricted to oxygen-dependent pathways, and is now known to be mediated by a number of additional metabolic and immune cues including metabolites and cytokines respectively...
October 4, 2016: Seminars in Immunology
Lyndsey Craven, Mary Herbert, Alison Murdoch, Julie Murphy, James Lawford Davies, Doug M Turnbull
No abstract text is available yet for this article.
February 2016: Stem Cells
Chris Cameron, Shannon Kelly, Shu-Ching Hsieh, Meghan Murphy, Li Chen, Ahmed Kotb, Joan Peterson, Doug Coyle, Becky Skidmore, Tara Gomes, Tammy Clifford, George Wells
BACKGROUND: Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs non-triptan migraine treatments. We conducted systematic reviews and network meta-analyses to compare the relative efficacy of triptans (alone or in combination with other drugs) for acute treatment of migraines compared with other triptan agents, non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or anti-emetics...
July 2015: Headache
Peter J Zed, Karen J L Black, Eleanor A Fitzpatrick, Stacy Ackroyd-Stolarz, Nancy G Murphy, Janet A Curran, Neil J MacKinnon, Doug Sinclair
BACKGROUND AND OBJECTIVE: There are few data on the rate and characterization of medication-related visits (MRVs) to the emergency department (ED) in pediatric patients. We sought to evaluate the frequency, severity, preventability, and classification of MRVs to the ED in pediatric patients. METHODS: We performed a prospective observational study of pediatric patients presenting to the ED over a 12-month period. A medication-related ED visit was identified by using pharmacist assessment, emergency physician assessment, and an independent adjudication committee...
March 2015: Pediatrics
John P Grady, Julie L Murphy, Emma L Blakely, Ronald G Haller, Robert W Taylor, Doug M Turnbull, Helen A L Tuppen
Accurate and reliable quantification of the abundance of mitochondrial DNA (mtDNA) molecules, both wild-type and those harbouring pathogenic mutations, is important not only for understanding the progression of mtDNA disease but also for evaluating novel therapeutic approaches. A clear understanding of the sensitivity of mtDNA measurement assays under different experimental conditions is therefore critical, however it is routinely lacking for most published mtDNA quantification assays. Here, we comprehensively assess the variability of two quantitative Taqman real-time PCR assays, a widely-applied MT-ND1/MT-ND4 multiplex mtDNA deletion assay and a recently developed MT-ND1/B2M singleplex mtDNA copy number assay, across a range of DNA concentrations and mtDNA deletion/copy number levels...
2014: PloS One
Doug Creighton, Mark Gruca, Douglas Marsh, Nancy Murphy
OBJECTIVES: Cervical mobilization and manipulation have been shown to improve cervical range of motion and pain. Rotatory thrust manipulation applied to the lower cervical segments is associated with controversy and the potential for eliciting adverse reactions (AR). The purpose of this clinical trial was to describe two translatory non-thrust mobilization techniques and evaluate their effect on cervical pain, motion restriction, and whether any adverse effects were reported when applied to the C7 segment...
November 2014: Journal of Manual & Manipulative Therapy
Leslie W Tari, Xiaoming Li, Michael Trzoss, Daniel C Bensen, Zhiyong Chen, Thanh Lam, Junhu Zhang, Suk Joong Lee, Grayson Hough, Doug Phillipson, Suzanne Akers-Rodriguez, Mark L Cunningham, Bryan P Kwan, Kirk J Nelson, Amanda Castellano, Jeff B Locke, Vickie Brown-Driver, Timothy M Murphy, Voon S Ong, Chris M Pillar, Dean L Shinabarger, Jay Nix, Felice C Lightstone, Sergio E Wong, Toan B Nguyen, Karen J Shaw, John Finn
Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes...
2013: PloS One
Myriam N Bouchlaka, Gail D Sckisel, Mingyi Chen, Annie Mirsoian, Anthony E Zamora, Emanual Maverakis, Danice E C Wilkins, Kory L Alderson, Hui-Hua Hsiao, Jonathan M Weiss, Arta M Monjazeb, Charles Hesdorffer, Luigi Ferrucci, Dan L Longo, Bruce R Blazar, Robert H Wiltrout, Doug Redelman, Dennis D Taub, William J Murphy
Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues...
October 21, 2013: Journal of Experimental Medicine
Isabel Barao, Paul W Wright, Can M Sungur, Stephen K Anderson, Doug Redelman, William J Murphy
Inhibitory natural killer (NK) cell receptors specific for major histocompatibility complex class I (MHC-I) molecules include Ly49 receptors in mice and killer immunoglobulin-like receptors (KIR) in humans. The "licensing" or "arming" models imply that engagement of these receptors to self MHC-I molecules during NK cell development educates NK cells to be more responsive to cancer and viral infection. We recently reported that hematopoietic stem cell transplantation (HSCT) induced rapid and preferential expansion of functionally competent Ly49G(+), but not other Ly49 family, NK cells independent of NK cell licensing via Ly49-MHC-I interactions...
October 2013: Biology of Blood and Marrow Transplantation
Sally Spendiff, Mojgan Reza, Julie L Murphy, Grainne Gorman, Emma L Blakely, Robert W Taylor, Rita Horvath, Georgia Campbell, Jane Newman, Hanns Lochmüller, Doug M Turnbull
Progressive myopathy is a major clinical feature of patients with mitochondrial DNA (mtDNA) disease. There is limited treatment available for these patients although exercise and other approaches to activate muscle stem cells (satellite cells) have been proposed. The majority of mtDNA defects are heteroplasmic (a mixture of mutated and wild-type mtDNA present within the muscle) with high levels of mutated mtDNA and low levels of wild-type mtDNA associated with more severe disease. The culture of satellite cell-derived myoblasts often reveals no evidence of the original mtDNA mutation although it is not known if this is lost by selection or simply not present in these cells...
December 1, 2013: Human Molecular Genetics
Antoinette R Bailey, Huayan Hou, Min Song, Demian F Obregon, Samantha Portis, Steven Barger, Doug Shytle, Saundra Stock, Takashi Mori, Paul G Sanberg, Tanya Murphy, Jun Tan
Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior...
September 2013: Glia
Peter J Zed, Christopher Haughn, Karen J L Black, Eleanor A Fitzpatrick, Stacy Ackroyd-Stolarz, Nancy G Murphy, Neil J MacKinnon, Janet A Curran, Doug Sinclair
OBJECTIVE: To review and describe the current literature pertaining to the incidence, classification, severity, preventability, and impact of medication-related emergency department (ED) and hospital admissions in pediatric patients. STUDY DESIGN: A systematic search of PubMED, Embase, and Web of Science was performed using the following terms: drug toxicity, adverse drug event, medication error, emergency department, ambulatory care, and outpatient clinic. Additional articles were identified by a manual search of cited references...
August 2013: Journal of Pediatrics
Myriam N Bouchlaka, Gail D Sckisel, Danice Wilkins, Emanual Maverakis, Arta M Monjazeb, Maxwell Fung, Lisbeth Welniak, Doug Redelman, Alan Fuchs, Cahit A Evrensel, William J Murphy
The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF) consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread...
2012: PloS One
Helen C Hancock, Helen Close, James M Mason, Jerry J Murphy, Ahmet Fuat, Raj Singh, Esther Wood, Mark de Belder, Gill Brennan, Nehal Hussain, Nitin Kumar, Doug Wilson, A Pali S Hungin
AIMS: Diagnosis of heart failure in older people in long-term care is challenging because of co-morbidities, cognitive deficit, polypharmacy, immobility, and poor access to services. This study aimed to ascertain heart failure prevalence and clinical management in this population. METHODS AND RESULTS: A total of 405 residents, aged 65-100 years, in 33 UK care facilities were prospectively enrolled between April 2009 and June 2010. The presence of heart failure was determined using European Society of Cardiology guidelines, modified where necessary for immobility...
February 2013: European Journal of Heart Failure
Julie L Murphy, Thiloka E Ratnaike, Ersong Shang, Gavin Falkous, Emma L Blakely, Charlotte L Alston, Tanja Taivassalo, Ronald G Haller, Robert W Taylor, Doug M Turnbull
An important diagnostic muscle biopsy finding in patients with mitochondrial DNA disease is the presence of respiratory-chain deficient fibres. These fibres are detected as cytochrome c oxidase-deficient following a sequential cytochrome c oxidase-succinate dehydrogenase reaction, often in a mosaic pattern within a population of cytochrome c oxidase-normal fibres. Detailed analysis of muscle biopsies from patients with various mitochondrial DNA defects shows that a spectrum of deficiency exists, as there are a large number of fibres which do not correspond to being either completely cytochrome c oxidase-normal (brown staining) or cytochrome c oxidase-deficient (blue staining)...
August 2012: Neuromuscular Disorders: NMD
Christina Curtis, Sohrab P Shah, Suet-Feung Chin, Gulisa Turashvili, Oscar M Rueda, Mark J Dunning, Doug Speed, Andy G Lynch, Shamith Samarajiwa, Yinyin Yuan, Stefan Gräf, Gavin Ha, Gholamreza Haffari, Ali Bashashati, Roslin Russell, Steven McKinney, Anita Langerød, Andrew Green, Elena Provenzano, Gordon Wishart, Sarah Pinder, Peter Watson, Florian Markowetz, Leigh Murphy, Ian Ellis, Arnie Purushotham, Anne-Lise Børresen-Dale, James D Brenton, Simon Tavaré, Carlos Caldas, Samuel Aparicio
The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs...
June 21, 2012: Nature
Julia K Tietze, Danice E C Wilkins, Gail D Sckisel, Myriam N Bouchlaka, Kory L Alderson, Jonathan M Weiss, Erik Ames, Kevin W Bruhn, Noah Craft, Robert H Wiltrout, Dan L Longo, Lewis L Lanier, Bruce R Blazar, Doug Redelman, William J Murphy
Memory T cells exhibit tremendous antigen specificity within the immune system and accumulate with age. Our studies reveal an antigen-independent expansion of memory, but not naive, CD8(+) T cells after several immunotherapeutic regimens for cancer resulting in a distinctive phenotype. Signaling through T-cell receptors (TCRs) or CD3 in both mouse and human memory CD8(+) T cells markedly up-regulated programmed death-1 (PD-1) and CD25 (IL-2 receptor α chain), and led to antigen-specific tumor cell killing...
March 29, 2012: Blood
Kai Sun, Maite Alvarez, Erik Ames, Isabel Barao, Mingyi Chen, Dan L Longo, Doug Redelman, William J Murphy
Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown...
February 9, 2012: Blood
Eric A Storch, Alessandro S De Nadai, Adam B Lewin, Joseph F McGuire, Anna M Jones, P Jane Mutch, R Doug Shytle, Tanya K Murphy
OBJECTIVE: To examine the optimal Yale Global Tic Severity Scale (YGTSS) percent reduction and raw cutoffs for predicting treatment response among children and adolescents with tic disorders. METHOD: Youth with a tic disorder (N=108; range=5-17 years) participated in several clinical trials involving varied medications or psychosocial treatment, or received naturalistic care. Assessments were conducted before and after treatment and included the YGTSS and response status on the Clinical Global Impressions-Improvement Scale (CGI-I)...
December 2011: Journal of Child and Adolescent Psychopharmacology
Isabel Barao, Maite Alvarez, Doug Redelman, Jonathan M Weiss, John R Ortaldo, Robert H Wiltrout, William J Murphy
Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution...
December 2011: Biology of Blood and Marrow Transplantation
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