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https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#1
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720697/inhibition-of-complement-c5-protects-against-organ-failure-and-reduces-mortality-in-a-baboon-model-of-escherichia-coli-sepsis
#2
Ravi Shankar Keshari, Robert Silasi, Narcis Ioan Popescu, Maulin Mukeshchandra Patel, Hala Chaaban, Cristina Lupu, K Mark Coggeshall, Tom Eirik Mollnes, Steven J DeMarco, Florea Lupu
Bacterial sepsis triggers robust activation of the complement system with subsequent generation of anaphylatoxins (C3a, C5a) and the terminal complement complex (TCC) that together contribute to organ failure and death. Here we tested the effect of RA101295, a 2-kDa macrocyclic peptide inhibitor of C5 cleavage, using in vitro whole-blood assays and an in vivo baboon model of Escherichia coli sepsis. RA101295 strongly inhibited E. coli-induced complement activation both in vitro and in vivo by blocking the generation of C5a and the soluble form of TCC, sC5b-9...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716517/lethal-suicide-attempt-with-a-mixed-drug-intoxication-of-metoprolol-and-propafenone-a-first-pediatric-case-report
#3
Ivana Kacirova, Milan Grundmann, Martin Kolek, Erika Vyskocilova-Hrudikova, Romana Urinovska, Petr Handlos
INTRODUCTION: The β1 adrenergic receptor blocker metoprolol is often prescribed together with the antiarrhythmic drug propafenone. Both are metabolized by cytochrome P450 2D6 and propafenone is also an inhibitor of this enzyme. We present a pediatric case showing metoprolol and propafenone intoxication in combination. CASE: A 14-year-old girl was admitted to a local emergency department after ingestion of metoprolol (probably 1g) and propafenone (probably 1.5-3g) in a suicide attempt...
June 29, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28713774/epic-immune-battles-of-history-neutrophils-vs-staphylococcus-aureus
#4
REVIEW
Fermin E Guerra, Timothy R Borgogna, Delisha M Patel, Eli W Sward, Jovanka M Voyich
Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28710749/express-fret-labeling-and-analysis-of-phagocytic-clearance
#5
Vladimir V Didenko
Lysosomal DNase II in phagocytic digestion produces DNA ends with 3'PO4/5'OH, which differ from those created in apoptotic DNA fragmentation, and can be used to label phagocytic clearance of cell death. Here, we describe the use of these specific DNA ends as selective markers of phagocytic reaction in cell suspensions. The approach does not require cell fixation. It selectively labels blunt-ended DNA breaks with terminal 5'OH. The detection is performed by ultra-fast FRET probes in a single step, closed-tube procedure...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28709650/anticoagulation-control-in-warfarin-treated-patients-undergoing-cardioversion-of-atrial-fibrillation-from-the-edoxaban-versus-enoxaparin-warfarin-in-patients-undergoing-cardioversion-of-atrial-fibrillation-trial
#6
Gregory Y H Lip, Naab Al-Saady, James Jin, Ming Sun, Michael Melino, Shannon M Winters, Dmitry Zamoryakhin, Andreas Goette
In the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation (ENSURE-AF) study (NCT 02072434), edoxaban was compared with enoxaparin-warfarin in 2,199 patients undergoing electrical cardioversion of nonvalvular atrial fibrillation (AF). In this multicenter prospective randomized open blinded end-point trial, we analyzed patients randomized to enoxaparin-warfarin. We determined time to achieve therapeutic range (TtTR); time in therapeutic range (TiTR); their clinical determinants; relation to sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) score; and impact on primary end points (composite of stroke, systemic embolic event[SEE], myocardial infarction [MI], and cardiovascular death [CVD] and composite of major + clinically relevant nonmajor bleeding)...
June 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#7
Derong Cui, Dawei Sun, Xintao Wang, Liye Yi, Ewa Kulikowicz, Michael Reyes, Junchao Zhu, Zeng-Jin Yang, Wei Jiang, Raymond C Koehler
To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702878/recent-trends-in-clot-retrieval-devices-a-review
#8
REVIEW
Aamir Hameed, Haroon Zafar, Darren Mylotte, Faisal Sharif
Stroke is the second leading cause of death worldwide and in Europe. Even with gold standard medical management of acute ischemic stroke, which is intravenous (IV) thrombolysis by administration of recombinant tissue plasminogen activator (rt-PA), the mortality rate remains the same. Intra-arterial (IA) thrombolysis therapy also did not achieve significant results and was not approved by the US Food and Drug Administration (FDA) because of limited sample size. This encouraged scientists and engineers to develop endovascular clot retrieval devices for the mechanical recanalization of the occluded arteries in stroke patients...
July 12, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28693501/knowledge-and-practice-of-immediate-newborn-care-among-health-care-providers-in-eastern-zone-public-health-facilities-tigray-ethiopia-2016
#9
Abadi Kidanemariam Berhe, Fitiwi Tinsae, Gebremedhin Gebreegziabher
BACKGROUND: According to WHO (2013) report the number of under five-year mortality in Ethiopia was 195,504, out of this 84,437 was from neonatal death and this mortality is related to immediate obstetric and newborn care of babies provided by health care providers; But little was known about the level of knowledge and practice related to immediate newborn care and their associated factors among health care providers generally in Tigray region and specifically in the Eastern Zone so the aim of this study was to assess knowledge and practice of immediate newborn care and associated factors among health care providers in the Eastern zone public health facilities, Tigray, Ethiopia...
July 11, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28692529/cyp2b6-genotypes-and-early-efavirenz-based-hiv-treatment-outcomes-in-botswana
#10
Robert Gross, Scarlett L Bellamy, Bakgaki Ratshaa, Xiaoyan Han, Marijana Vujkovic, Richard Aplenc, Andrew P Steenhoff, Mosepele Mosepele, Ganesh Moorthy, Athena F Zuppa, Brian L Strom, Gregory P Bisson
OBJECTIVES: To determine the association between cytochrome p450 2B6 genotypes and efavirenz-based HIV treatment outcomes. DESIGN: Observational cohort study of HIV infected adults initiating efavirenz-based regimens in Botswana. METHODS: The primary endpoint was a composite of death or loss to care or HIV RNA>25 copies/ml at 6 months. CYP2B6 516G>T and 983T>C genotyping was done with Taqman Open Array platform. Adverse experiences were measured using the Subject Experience Questionnaire...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28691411/kupffer-cell-in-the-immune-activation-and-tolerance-toward-hbv-hcv-infection
#11
REVIEW
Yuan Fangchao, Zhang Wenfeng, Mu Di, Gong Jianping
Kupffer cells(KCs) largely found in the sinusoids are the macrophages which specifically reside in liver. KC is a crucial part of innate immune system, acting as scavenger and phagocyte. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in immune response, but also facilitate the pathogenesis of type B and type C hepatitis through their antigen-presenting function and secretion of soluble mediators. KCs can express TLRs (Toll-like receptors), FasL, Programmed cell death ligand 1 (PD-L1) and secrete large amount of inflammatory factors to lead to the tolerant state of immune response toward HBV/HCV...
June 27, 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28686526/in-life-there-is-death-how-epithelial-tissue-barriers-are-preserved-despite-the-challenge-of-apoptosis
#12
Kinga Duszyc, Guillermo A Gomez, Kate Schroder, Matthew J Sweet, Alpha S Yap
Apoptosis is a ubiquitous mode of programmed cell death that is found in healthy organs and can be stimulated by many toxic stresses. When it occurs in epithelia, apoptosis presents major challenges to tissue integrity. Apoptotic corpses can promote inflammatory and autoimmune responses if they are retained, and the cellular fragmentation that accompanies apoptosis can potentially compromise the epithelial barrier. Here we discuss 2 homeostatic mechanisms that allow epithelia to circumvent these potential risks: clearance of apoptotic corpses by professional and non-professional phagocytes and physical expulsion of apoptotic cells by apical extrusion...
June 28, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28682899/simple-resection-of-the-lesion-bile-duct-branch-for-treatment-of-regional-hepatic-bile-duct-stones
#13
Li Enliang, Wu Rongshou, Shi Shidai, Zhang Jingling, Feng Qian, Liao Wenjun, Wu Linquan
To evaluate the effectiveness and safety of simple resections of bile duct branch lesions for the treatment of regional hepatic bile duct stones.A retrospective analysis of the clinical data from patients in our hospital from November 2008 to November 2015, who only underwent a simple resection of the lesion bile duct branch. The patients' clinical characteristics, surgical features, postoperative complications, stone clear rate, residual stone rate, and recurrence stone rate were analyzed.This study of 32 patients included 13 males and 19 females with intrahepatic bile duct stones confined to the right hepatic bile duct branch...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28679745/maternal-antiviral-immunoglobulin-accumulates-in-neural-tissue-of-neonates-to-prevent-hsv-neurological-disease
#14
Yike Jiang, Chaya D Patel, Richard Manivanh, Brian North, Iara M Backes, David A Posner, Francesca Gilli, Andrew R Pachner, Lananh N Nguyen, David A Leib
While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection...
July 5, 2017: MBio
https://www.readbyqxmd.com/read/28679535/small-molecule-based-inhibition-of-mek1-2-proteins-dampens-inflammatory-responses-to-malaria-reduces-parasite-load-and-mitigates-pathogenic-outcomes
#15
Xianzhu Wu, Kiran K Dayanand, Ramesh P Thylur, Christopher C Norbury, D Channe Gowda
Malaria infections cause several systemic and severe single or multi-organ pathologies, killing hundreds of thousands of people annually. Considering the existing widespread resistance of malaria parasites to antiparasitic drugs and their high propensity to develop drug resistance, alternative strategies are required to manage malaria infections. Since malaria is a host immune response-driven disease, one approach is based on gaining a detailed understanding of the molecular and cellular processes that modulate malaria-induced innate and adaptive immune responses...
July 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28672087/interventions-for-chronic-kidney-disease-in-people-with-sickle-cell-disease
#16
REVIEW
Noemi Ba Roy, Patricia M Fortin, Katherine R Bull, Carolyn Doree, Marialena Trivella, Sally Hopewell, Lise J Estcourt
BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD.Chronic kidney disease is defined as abnormalities of kidney structure or function, present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD...
July 3, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28669393/eryptosis-in-health-and-disease-a-paradigm-shift-towards-understanding-the-patho-physiological-implications-of-programmed-cell-death-of-erythrocytes
#17
REVIEW
Syed M Qadri, Rosi Bissinger, Ziad Solh, Per-Arne Oldenborg
During the course of their natural ageing and upon injury, anucleate erythrocytes can undergo an unconventional apoptosis-like cell death, termed eryptosis. Eryptotic erythrocytes display a plethora of morphological alterations including volume reduction, membrane blebbing and breakdown of the membrane phospholipid asymmetry resulting in phosphatidylserine externalization which, in turn, mediates their phagocytic recognition and clearance from the circulation. Overall, the eryptosis machinery is tightly orchestrated by a wide array of endogenous mediators, ion channels, membrane receptors, and a host of intracellular signaling proteins...
June 17, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28667037/a-programmed-cell-death-1-haplotype-is-associated-with-clearance-of-hepatitis-b-virus
#18
Zhouhua Hou, Qing Zhou, Menghou Lu, Deming Tan, Xuwen Xu
PURPOSE: Programmed cell death 1 (PD-1) is an important immune checkpoint of T cells response and plays a critical role in chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the associations between PD-1 polymorphisms and susceptibility and disease progression of chronic HBV infection. METHODS: In this case-control study, 299 cases with chronic HBV infection comprised of 99 asymptomatic carriers (ASCs), 96 patients with chronic hepatitis B (CHB), and 104 patients with HBV-related acute on chronic liver failure (HBV-ACLF) were enrolled...
May 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28665999/analysis-of-the-role-of-intratecal-liposomal-cytarabine-in-the-prophylaxis-and-treatment-of-central-nervous-system-lymphomatosis-the-balearic-lymphoma-group-experience
#19
Marta García-Recio, Antonia Cladera, Leyre Bento, Julia Dominguez, Silvia Ruiz de Gracia, Francesca Sartori, Raquel Del Campo, Lucia García, Carmen Ballester, Jordi Gines, Joan Bargay, Antonia Sampol, Antonio Gutiérrez
Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20-30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28663335/mitochondrial-quality-control-in-alveolar-epithelial-cells-damaged-by-s-aureus-pneumonia-in-mice
#20
Hagir B Suliman, Bryan D Kraft, Raquel R Bartz, Lingye Chen, Karen E Welty-Wolf, Claude A Piantadosi
(242 words) Mitochondrial damage is often overlooked in acute lung injury (ALI), but most of the lung's physiological processes, such as airway tone, muco-ciliary clearance, Va/Q matching, and immune surveillance require aerobic energy provision. Because the cell's processes of mitochondrial quality control (QC) regulate the elimination and replacement of damaged mitochondria to support cell survival, we evaluated mitochondrial biogenesis and mitophagy in the alveolar region of mice in a validated S. aureus pneumonia model...
June 29, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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