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https://www.readbyqxmd.com/read/28219442/eplerenone-for-early-cardiomyopathy-in-duchenne-muscular-dystrophy-results-of-a-two-year-open-label-extension-trial
#1
Subha V Raman, Kan N Hor, Wojciech Mazur, Xin He, John T Kissel, Suzanne Smart, Beth McCarthy, Sharon L Roble, Linda H Cripe
BACKGROUND: Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. RESULTS: Eleven subjects (phase 1 baseline median [range] age: 13 [7 - 25] years) from the original 12-month trial at a single participating center were enrolled...
February 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28211135/the-role-of-peginterferon-in-nucleos-t-ide-analogue-treated-chronic-hepatitis-b-patients-a-review-of-published-literature
#2
Wenhong Zhang, Qing Xie, Qin Ning, Xiaoguang Dou, Xinyue Chen, Jidong Jia, Yi Xie, Hong Ren
Chronic hepatitis B infection (CHB) causes up to 1.0 million deaths annually. Currently, more than 90% of CHB patients worldwide are receiving indefinite nucleos(t)ide analogue (NA) therapy. New strategies for optimizing hepatitis B surface antigen (HBsAg) loss are required for NA-treated patients as the majority are unable to achieve HBsAg loss and may require lifelong therapy. In hepatitis B e antigen (HBeAg)-positive patients, switching from NAs to finite peginterferon (PegIFN) therapy can double HBeAg seroconversion rates...
February 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28201921/generalized-spin-ratio-scaled-mp2-method-for-accurate-prediction-of-intermolecular-interactions-for-neutral-and-ionic-species
#3
Samuel Tan, Santiago Barrera Acevedo, Ekaterina I Izgorodina
The accurate calculation of intermolecular interactions is important to our understanding of properties in large molecular systems. The high computational cost of the current "gold standard" method, coupled cluster with singles and doubles and perturbative triples (CCSD(T), limits its application to small- to medium-sized systems. Second-order Møller-Plesset perturbation (MP2) theory is a cheaper alternative for larger systems, although at the expense of its decreased accuracy, especially when treating van der Waals complexes...
February 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28192403/a-double-negative-feedback-loop-between-epcam-and-erk-contributes-to-the-regulation-of-epithelial-mesenchymal-transition-in-cancer
#4
N V Sankpal, T P Fleming, P K Sharma, H J Wiedner, W E Gillanders
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28182325/genetic-basis-of-between-individual-and-within-individual-variance-of-docility
#5
Julien G A Martin, Enrico Pirottay, Matthew B Petellez, Daniel T Blumstein
Between-individual variation in phenotypes within a population is the basis of evolution. However, evolutionary and behavioural ecologists have mainly focused on estimating between-individual variance in mean trait and neglected variation in within-individual variance, or predictability of a trait. In fact, an important assumption of mixed-effects models used to estimate between-individual variance in mean traits is that within-individual residual variance (predictability) is identical across individuals. Individual heterogeneity in the predictability of behaviours is a potentially important effect but rarely estimated and accounted for...
February 9, 2017: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/28176175/safety-and-immunogenicity-of-neoadjuvant-treatment-using-wt1-immunotherapeutic-in-combination-with-standard-therapy-in-patients-with-wt1-positive-stage-ii-iii-breast-cancer-a-randomized-phase-i-study
#6
M Higgins, G Curigliano, V Dieras, S Kuemmel, G Kunz, P A Fasching, M Campone, T Bachelot, P Krivorotko, S Chan, A Ferro, L Schwartzberg, M Gillet, P M De Sousa Alves, V Wascotte, F F Lehmann, P Goss
PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy)...
February 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28174027/forkhead-box-p3-regulatory-t-cells-and-toll-like-receptor-2-co-expression-in-oral-squamous-cell-carcinoma
#7
H M Hussaini, V P B Parachuru, G J Seymour, A M Rich
BACKGROUND: The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3(+)cells, TLR2(+) cells and double-labelled FoxP3(+)TLR2(+) immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF)...
February 4, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28166225/the-composition-of-t-cell-subtypes-in-duodenal-biopsies-are-altered-in-coeliac-disease-patients
#8
Janni V Steenholt, Christian Nielsen, Leen Baudewijn, Anne Staal, Karina S Rasmussen, Hardee J Sabir, Torben Barington, Steffen Husby, Henrik Toft-Hansen
One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+) and the number of CD3+ CD4- CD8- double-negative (DN) T cells were elevated 6-7 fold in children with CD...
2017: PloS One
https://www.readbyqxmd.com/read/28159903/cd31-a-valuable-marker-to-identify-early-and-late-stages-of-t-cell-differentiation-in-the-human-thymus
#9
Marc Douaisi, Rachel S Resop, Maho Nagasawa, Joshua Craft, Beth D Jamieson, Bianca Blom, Christel H Uittenbogaart
Although CD31 expression on human thymocytes has been reported, a detailed analysis of CD31 expression at various stages of T cell development in the human thymus is missing. In this study, we provide a global picture of the evolution of CD31 expression from the CD34(+) hematopoietic precursor to the CD45RA(+) mature CD4(+) and CD8(+) single-positive (SP) T cells. Using nine-color flow cytometry, we show that CD31 is highly expressed on CD34(+) progenitors and stays high until the early double-positive stage (CD3(-)CD4(+)CD8α(+)β(-))...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159608/safety-and-efficacy-of-the-c-tb-skin-test-to-diagnose-mycobacterium-tuberculosis-infection-compared-with-an-interferon-%C3%AE-release-assay-and-the-tuberculin-skin-test-a-phase-3-double-blind-randomised-controlled-trial
#10
Morten Ruhwald, Henrik Aggerbeck, Rafael Vázquez Gallardo, Søren T Hoff, José I Villate, Bettine Borregaard, José A Martinez, Ingrid Kromann, Antón Penas, Luis L Anibarro, Maria Luiza de Souza-Galvão, Francisca Sánchez, Jose Ángel Rodrigo-Pendás, Antoni Noguera-Julian, Xavier Martínez-Lacasa, Maria Victoria Tuñez, Virginia Leiro Fernández, Joan P Millet, Antonio Moreno, Nazaret Cobos, José M Miró, Llanos Roldan, Angels Orcau, Peter Andersen, Joan A Caylá
BACKGROUND: Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. METHODS: Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain...
January 31, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28159235/commercial-gold-nanocolloid-inhibits-synthesis-of-il-2-and-proliferation-of-porcine-t-lymphocytes
#11
Joanna Małaczewska, Roman Wójcik, Edyta Kaczorek, Wojciech Rękawek, Andrzej Krzysztof Siwicki
Recent intensive development of nanotechnology has broadened the use of noble metal nanocolloids in alternative medicine. Meanwhile, silver and copper nanoparticles are tested as potential feed additives in pig farming. Experiments on rodents prove that metal nanocolloids easily interact with macrophages and lymphocytes, although the specific nature of pigs' immune system means that rodent tests may not reflect fully the responsiveness of porcine T cells. Our purpose was to demonstrate the effect of a commercial gold nanocolloid on percentages and proliferation of T lymphocyte subpopulations and on IL-2 and IL-10 synthesis in porcine peripheral blood mononuclear cells tested in vitro...
February 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28149711/hepatic-caveolin-1-is-enhanced-in-cyp27a1-apoe-double-knockout-mice
#12
Line Zurkinden, Yosef T Mansour, Beatrice Rohrbach, Bruno Vogt, Hiten D Mistry, Geneviève Escher
Sterol 27-hydroxylase (CYP27A1) is involved in bile acid synthesis and cholesterol homoeostasis. Cyp27a1((-/-))/Apolipoprotein E((-/-)) double knockout mice (DKO) fed a western diet failed to develop atherosclerosis. Caveolin-1 (CAV-1), the main component of caveolae, is associated with lipid homoeostasis and has regulatory roles in vascular diseases. We hypothesized that liver CAV-1 would contribute to the athero-protective mechanism in DKO mice. Cyp27a1((+/+))/ApoE((-/-)) (ApoE KO), Cyp27a1((+/-))/ApoE((-/-)) (het), and DKO mice were fed a western diet for 2 months...
October 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28138401/t-cadherin-in-prostate-cancer-relationship-with-cancer-progression-differentiation-and-drug-resistance
#13
Boris Dasen, Tatjana Vlajnic, Chantal Mengus, Christian Ruiz, Lukas Bubendorf, Giulio Spagnoli, Stephen Wyler, Paul Erne, Thérèse J Resink, Maria Philippova
Prostate cancer represents the second leading cause of cancer-related death in men. T-cadherin (CDH13) is an atypical GPI-anchored member of the cadherin family of adhesion molecules. Its gene was reported to be downregulated in a small series of prostate tumours. T-cadherin protein expression/localisation in prostate tissue has never been investigated. The purpose of our study was to analyse CDH13 gene and protein levels in large sets of healthy and cancer prostate tissue specimens and evaluate CDH13 effects on the sensitivity of prostate cancer cells to chemotherapy...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28137643/mlf1-is-a-proapoptotic-antagonist-of-hop-complex-mediated-survival
#14
Yi Sun, Jyh-Rong Chao, Wu Xu, Alan Pourpak, Kelli Boyd, Simon Moshiach, Guo-Yan Qi, Amina Fu, Hua-Rong Shao, Stanley Pounds, Stephan W Morris
In the HAX1/HtrA2-OMI/PARL (HOP) mitochondrial protein complex, anti-apoptotic signals are generated by cleavage and activation of the serine protease HtrA2/OMI by the rhomboid protease PARL upon recruitment of both proteases to inner mitochondrial membrane protein HAX1 (HS1-associated protein X-1). Here we report the negative regulation of the HOP complex by human leukemia-associated myeloid leukemia factor 1 (MLF1). We demonstrate that MLF1 physically and functionally associates with HAX1 and HtrA2. Increased interaction of MLF1 with HAX1 and HtrA2 displaces HtrA2 from the HOP complex and inhibits HtrA2 cleavage and activation, resulting in the apoptotic cell death...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28135253/alternative-pathway-for-the-development-of-v%C3%AE-14-nkt-cells-directly-from-cd4-cd8-thymocytes-that-bypasses-the-cd4-cd8-stage
#15
Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi
Although invariant Vα14(+) natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28129978/synthesis-and-biological-evaluation-of-2-alkoxycarbonylallyl-esters-as-potential-anticancer-agents
#16
Conor T Ronayne, Lucas N Solano, Grady L Nelson, Erica A Lueth, Skyler L Hubbard, Tanner J Schumacher, Zachary S Gardner, Sravan K Jonnalagadda, Shirisha Gurrapu, Jon Holy, Venkatram R Mereddy
The reaction of carboxylic acids with Baylis-Hillman reaction derived α-bromomethyl acrylic esters readily provide 2-(alkoxycarbonyl)allyl esters in good to excellent yields. These functionalized allyl esters have been evaluated for their cell proliferation inhibition properties against breast cancer (MDA-MB-231 and 4T1) and pancreatic cancer (MIAPaCa-2) cell lines to explore their potential as anticancer agents. Several of the synthesized derivatives exhibit good potency against all three cancer cell lines...
January 17, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28128277/primary-cutaneous-aggressive-epidermotropic-cytotoxic-t-cell-lymphomas-reappraisal-of-a-provisional-entity-in-the-2016-who-classification-of-cutaneous-lymphomas
#17
Joan Guitart, M Estela Martinez-Escala, Antonio Subtil, Madeleine Duvic, Melissa P Pulitzer, Elise A Olsen, Ellen Kim, Alain H Rook, Sara S Samimi, Gary S Wood, Michael Girardi, Jacqueline Junkins-Hopkins, Doina S Ivan, M Angelica Selim, Kimberly A Sable, Pooja Virmani, Laura B Pincus, Michael T Tetzlaff, Jinah Kim, Youn H Kim
Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement...
January 27, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28126732/effects-of-n-acetyl-seryl-asparyl-lysyl-proline-on-blood-pressure-renal-damage-and-mortality-in-systemic-lupus-erythematosus
#18
Pablo Nakagawa, Juan X Masjoan-Juncos, Heba Basha, Branislava Janic, Morel E Worou, Tang-Dong Liao, Cesar A Romero, Edward L Peterson, Oscar A Carretero
Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE-Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac-SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE-Hyp, Ac-SDKP prevents hypertension and renal damage by modulating T cells...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28121722/omega-3-supplementation-and-the-neural-correlates-of-negative-affect-and-impulsivity-a-double-blind-randomized-placebo-controlled-trial-in-midlife-adults
#19
Annie T Ginty, Matthew F Muldoon, Dora C H Kuan, Brittney Schirda, Thomas W Kamarck, J Richard Jennings, Stephen B Manuck, Peter J Gianaros
OBJECTIVE: In clinical trials, omega-3 fatty acid supplementation improves symptoms in psychiatric disorders involving dysregulated mood and impulse control, yet it is unclear whether in healthy adults omega-3 fatty acid supplementation affects mood, impulse control and the brain systems supporting these processes. Accordingly, this study tested the hypotheses that eciosapentaenoic (EPA) and docosahexaenoic (DHA) acid supplementation reduces negative affect and impulsive behaviors in healthy adults and that these changes correspond to alterations in corticolimbic and corticostriatal brain systems which support affective and impulsive processes...
January 24, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#20
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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