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T cell age

Zhihong Hu, L Jeffrey Medeiros, Zi Chen, Weina Chen, Shaoying Li, Sergej N Konoplev, Xinyan Lu, Lan V Pham, Ken H Young, Wei Wang, Shimin Hu
MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy...
October 21, 2016: American Journal of Surgical Pathology
Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamas Fulop, Janet E McElhaney, Melissa K Andrew, Stephen D Walter, P J Devereaux, Mehrnoush Malek, Ryan R Brinkman, Jonathan Bramson, Mark Loeb
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female)...
October 24, 2016: Journal of the American Geriatrics Society
Cameron Browne
This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Chunxia Peng, Wei Wang, Quangang Xu, Mo Yang, Huangfen Zhou, Shuo Zhao, Shihui Wei
PURPOSE: The aim of this study was to evaluate the differences between macular inner retinal layers and peripapillary retinal nerve fibre layer (pRNFL) thickness in Chinese patients with neuromyelitis spectrum optic neuritis (NMOSD-ON) and isolated optic neuritis (ION) with only one episode. METHODS: This cross-sectional study included 35 patients (35 eyes) with NMOSD-ON (NMO-IgG seropositive) and 46 patients (46 eyes) with ION after one episode. Spectral domain optical coherence tomography (SD-OCT) was used to quantify pRNFL, macular RNFL (mRNFL), ganglion cell and inner plexiform layers (GCIPL) and inner nuclear layer (INL) thickness using an automated algorithm...
October 24, 2016: Acta Ophthalmologica
Soo Young Kim, Min Seok Hur, Byung Gon Choi, Min Jung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Psoriasis is a polygenic and multifactorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin 17A (IL-17A), interleukin 17 receptor (IL-17R), and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
October 24, 2016: Clinical and Experimental Immunology
Adriaan A van Beek, Bruno Sovran, Floor Hugenholtz, Ben Meijer, Joanne A Hoogerland, Violeta Mihailova, Corine van der Ploeg, Clara Belzer, Mark V Boekschoten, Jan H J Hoeijmakers, Wilbert P Vermeij, Paul de Vos, Jerry M Wells, Pieter J M Leenen, Claudio Nicoletti, Rudi W Hendriks, Huub F J Savelkoul
Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1(-/Δ7) mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1(-/Δ7) mice was characterized by a thin (< 10 μm) mucus layer...
2016: Frontiers in Immunology
Alexander J Sweidan, Navneet K Singh, Natasha Dang, Vinh Lam, Jyoti Datta
INTRODUCTION: Amiodarone is often used in the suppression of tachyarrhythmias. One of the more serious adverse effects includes amiodarone pulmonary toxicity (APT). Several pulmonary diseases can manifest including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary nodules or masses, and pleural effusion. Incidence of APT varies from 5-15% and is correlated to dosage, age of the patient, and preexisting lung disease...
2016: Clinical Medicine Insights. Case Reports
Waleska K Martins, Andreza B Gomide, Érico T Costa, Helena C Junqueira, Beatriz S Stolf, Rosangela Itri, Maurício S Baptista
BACKGROUND: Cell senescence is a process of central importance to the understanding of aging as well as to the development of new drugs. It is related with genomic instability, which has been shown to occur in the presence of autophagy deficiency. Yet, the mechanism that triggers genomic instability and senescence from a condition of autophagy deficiency remains unknown. By analyzing the consequences of treating human keratinocytes (HaCaT) with the pentacyclic triterpenoid Betulinic Acid (BA) we were able to propose that cell senescence can develop as a response to parallel damage in the membranes of mitochondria and lysosome...
October 20, 2016: Biochimica et Biophysica Acta
Daniël A Korevaar, Laurence M Crombag, Jérémie F Cohen, René Spijker, Patrick M Bossuyt, Jouke T Annema
BACKGROUND: Guidelines recommend endosonography with fine-needle aspiration for mediastinal nodal staging in non-small-cell lung cancer, but most do not specify whether this should be through endobronchial endoscopy (EBUS), oesophageal endoscopy (EUS), or both. We assessed the added value and diagnostic accuracy of the combined use of EBUS and EUS. METHODS: For this systematic review and random effects meta-analysis, we searched MEDLINE, Embase, BIOSIS Previews, and Web of Science, without language restrictions, for studies published between Jan 1, 2000, and Feb 25, 2016...
October 20, 2016: Lancet Respiratory Medicine
Ken M Kunisaki, Dennis E Niewoehner, Gary Collins, Bitten Aagaard, Nafisah B Atako, Elzbieta Bakowska, Amanda Clarke, Giulio Maria Corbelli, Ernest Ekong, Sean Emery, Elizabeth B Finley, Eric Florence, Rosa M Infante, Cissy M Kityo, Juan Sierra Madero, Daniel E Nixon, Ellen Tedaldi, Jørgen Vestbo, Robin Wood, John E Connett
BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. METHODS: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries...
October 20, 2016: Lancet Respiratory Medicine
Jyotiska Chaudhuri, Neelanjan Bose, Jianke Gong, David Hall, Alexander Rifkind, Dipa Bhaumik, T Harshani Peiris, Manish Chamoli, Catherine H Le, Jianfeng Liu, Gordon J Lithgow, Arvind Ramanathan, X Z Shawn Xu, Pankaj Kapahi
Reactive α-dicarbonyls (α-DCs), like methylglyoxal (MGO), accumulate with age and have been implicated in aging and various age-associated pathologies, such as diabetic complications and neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Evolutionarily conserved glyoxalases are responsible for α-DC detoxification; however, their core biochemical regulation has remained unclear. We have established a Caenorhabditis elegans model, based on an impaired glyoxalase (glod-4/GLO1), to broadly study α-DC-related stress...
October 12, 2016: Current Biology: CB
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
Verena Clarissa Samara, Adam de Havenon
Acute myelopathy is a rare presentation of systemic T-cell lymphoma. We present the case of a man aged 68 years with a diffuse erythematous maculopapular rash, followed by lower extremity paresthesias and progressive lower extremity weakness. Spinal MRI showed longitudinally extensive T2 hyperintensity with diffuse contrast enhancement. An atypical clonal T-lymphocyte population was identified in cerebrospinal fluid, peripheral blood and bone marrow aspirate, indicating a malignant T-cell lymphoproliferative disorder...
October 21, 2016: BMJ Case Reports
Anthony L Cunningham, Nathalie Garçon, Oberdan Leo, Leonard R Friedland, Richard Strugnell, Béatrice Laupèze, Mark Doherty, Peter Stern
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response...
October 18, 2016: Vaccine
Greg Hodge, Eugene Roscioli, Hubertus Jersmann, Hai B Tran, Mark Holmes, Paul N Reynolds, Sandra Hodge
BACKGROUND: Corticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD...
October 21, 2016: Respiratory Research
Allegra T Aron, Morten O Loehr, Jana Bogena, Christopher J Chang
Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands-the labile iron pool-to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron...
October 21, 2016: Journal of the American Chemical Society
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
R C Gerring, C T Ott, J M Curry, Z B Sargi, S T Wester
PurposeTo describe prognostic factors and survival outcomes in patients who underwent orbital exenteration for periocular non-melanoma cutaneous malignancies.MethodsThe authors performed an institutional review board-approved retrospective review of all patients who underwent orbital exenteration for non-melanoma periocular cutaneous malignancies at a tertiary care hospital system over a 10-year period. Patient demographics, tumor, and treatment data were recorded. Survival outcomes included disease-free survival (DFS) and overall survival (OS)...
October 21, 2016: Eye
J R Baker, C Vuppusetty, T Colley, Andriana I Papaioannou, P Fenwick, Louise Donnelly, K Ito, P J Barnes
Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD...
October 21, 2016: Scientific Reports
Michael M Dowling, Charles T Quinn, Claudio Ramaciotti, Julie Kanter, Ifeyinwa Osunkwo, Baba Inusa, Rathi Iyer, Janet L Kwiatkowski, Clarissa Johnson, Melissa Rhodes, William Owen, John J Strouse, Julie A Panepinto, Lynne Neumayr, Sharada Sarnaik, Patricia A Plumb, Nomazulu Dlamini, Fenella Kirkham, Linda S Hynan
'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male)...
October 21, 2016: British Journal of Haematology
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