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https://www.readbyqxmd.com/read/28212662/marked-central-nervous-system-pathology-in-cd59-knockout-rats-following-passive-transfer-of-neuromyelitis-optica-immunoglobulin-g
#1
Xiaoming Yao, Alan S Verkman
Neuromyelitis optica spectrum disorders (herein called NMO) is an inflammatory demyelinating disease of the central nervous system in which pathogenesis involves complement-dependent cytotoxicity (CDC) produced by immunoglobulin G autoantibodies targeting aquaporin-4 (AQP4-IgG) on astrocytes. We reported evidence previously, using CD59(-/-) mice, that the membrane-associated complement inhibitor CD59 modulates CDC in NMO (Zhang and Verkman, J. Autoimmun. 53:67-77, 2014). Motivated by the observation that rats, unlike mice, have human-like complement activity, here we generated CD59(-/-) rats to investigate the role of CD59 in NMO and to create NMO pathology by passive transfer of AQP4-IgG under conditions in which minimal pathology is produced in normal rats...
February 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28197649/dose-response-relationship-of-temozolomide-determined-by-the-pig-a-comet-and-micronucleus-assay
#2
M Guérard, G Johnson, S Dertinger, G Duran-Pacheco, J Funk, A Zeller
Temozolomide (TMZ), a monofunctional alkylating agent, was selected as a model compound to determine its quantitative genotoxic dose-response relationship in different tissues (blood, liver, and jejunum) and endpoints [Pig-a-, comet-, and micronucleus assay (MNT)] in male rats. TMZ was administered p.o. over 5 consecutive days (day 1-5), followed by a treatment-free period of 50 days (day 6-56) and a final administration prior to necropsy (day 57-59). TMZ showed a dose-dependent increase in DNA damage in all interrogated endpoints...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28154563/host-immune-evasion-by-lyme-and-relapsing-fever-borreliae-findings-to-lead-future-studies-for-borrelia-miyamotoi
#3
REVIEW
Brandee L Stone, Catherine A Brissette
The emerging pathogen, Borrelia miyamotoi, is a relapsing fever spirochete vectored by the same species of Ixodes ticks that carry the causative agents of Lyme disease in the US, Europe, and Asia. Symptoms caused by infection with B. miyamotoi are similar to a relapsing fever infection. However, B. miyamotoi has adapted to different vectors and reservoirs, which could result in unique physiology, including immune evasion mechanisms. Lyme Borrelia utilize a combination of Ixodes-produced inhibitors and native proteins [i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28140725/complement-dependent-cytotoxicity-induced-by-therapeutic-antibodies-in-b-cell-acute-lymphoblastic-leukemia-is-dictated-by-target-antigen-expression-levels-and-augmented-by-loss-of-membrane-bound-complement-inhibitors
#4
Floris C Loeff, H M Esther van Egmond, Bart A Nijmeijer, J H Frederik Falkenburg, Constantijn J Halkes, Inge Jedema
To optimally utilize therapeutic monoclonal antibodies in the treatment of B-cell acute lymphoblastic leukemia (B-ALL) understanding their mechanisms of action and the factors influencing these mechanisms is required. We show strong correlations between target antigen expression levels and sensitivity to complement-dependent cytotoxicity (CDC) induced by rituximab, ofatumumab, or alemtuzumab in a panel of cell lines derived from primary B-ALL cells and in primary B-ALL samples. Simultaneous loss of expression of membrane-bound complement regulatory proteins (mCRP) CD55 and CD59 due to glycophosphatidylinositol-anchor deficiency, significantly increased sensitivity to CDC...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28036279/proteins-that-interact-with-calgranulin-b-in-the-human-colon-cancer-cell-line-hct-116
#5
Jae Kyung Myung, Seung-Gu Yeo, Kyung Hee Kim, Kwang-Soo Baek, Daye Shin, Jong Heon Kim, Jae Youl Cho, Byong Chul Yoo
Calgranulin B is released from immune cells and can be internalized into colon cancer cells to prevent proliferation. The present study aimed to identify proteins that interact with calgranulin B to suppress the proliferation of colon cancer cells, and to obtain information on the underlying anti-tumor mechanism(s) of calgranulin B. Calgranulin B expression was induced in colon cancer cell line HCT-116 by infection with calgranulin B-FLAG expressing lentivirus, and it led to a significant suppression of cell proliferation...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28017655/cd59-regulation-by-sox2-is-required-for-epithelial-cancer-stem-cells-to-evade-complement-surveillance
#6
Jianfeng Chen, Peipei Ding, Ling Li, Hongyu Gu, Xin Zhang, Long Zhang, Na Wang, Lu Gan, Qi Wang, Wei Zhang, Weiguo Hu
Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/27994808/effects-of-benzo-e-pyrene-on-reactive-oxygen-nitrogen-species-and-inflammatory-cytokines-induction-in-human-rpe-cells-and-attenuation-by-mitochondrial-involved-mechanism
#7
M Fernanda Estrago-Franco, M Tarek Moustafa, Mohammad Riazi-Esfahani, Ashish U Sapkal, Rhina Piche-Lopez, A Jayaprakash Patil, Ashish Sharma, Payam Falatoonzadeh, Marilyn Chwa, Georgia Luczy-Bachman, Baruch D Kuppermann, M Cristina Kenney
PURPOSE: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay...
October 2016: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/27979168/differences-in-proteomic-profiles-of-milk-fat-globule-membrane-in-yak-and-cow-milk
#8
Xiaoxi Ji, Xisheng Li, Ying Ma, Day Li
Milk fat globule membrane (MFGM) is an important milk component which is rich in bioactive proteins. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach was used to investigate the differences in the MFGM proteins between yak and cow milk. Over 450 proteins were identified between the yak and cow MFGM. The MFGM proteins with significant differences were compared based on the relative abundance. Proteins such as Glycosylation-dependent cell adhesion molecule 1 (GlyCAM1), CD59 molecule and lactadherin, were identified having a much higher abundance (4...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27942176/identification-of-urinary-proteins-potentially-associated-with-diabetic-kidney-disease
#9
R K Marikanty, M K Gupta, S V B Cherukuvada, S S S Kompella, A K Prayaga, S Konda, R V Polisetty, M M Idris, P V Rao, G R Chandak, K V Dakshinamurty
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Although several parameters are used to evaluate renal damage, in many instances, there is no pathological change until damage is already advanced. Mass spectrometry-based proteomics is a novel tool to identify newer diagnostic markers. To identify urinary proteins associated with renal complications in diabetes, we collected urine samples from 10 type 2 diabetes patients each with normoalbuminuria, micro- and macro-albuminuria and compared their urinary proteome with that of 10 healthy individuals...
November 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27932991/cannabidiol-modulates-the-immunophenotype-and-inhibits-the-activation-of-the-inflammasome-in-human-gingival-mesenchymal-stem-cells
#10
Rosaliana Libro, Domenico Scionti, Francesca Diomede, Marco Marchisio, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5 μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27931820/evaluation-for-a-mutagenicity-of-aristolochic-acid-by-pig-a-and-pigret-assays-in-rats
#11
Naomi Koyama, Yutaka Yonezawa, Michi Nakamura, Hisakazu Sanada
The Pig-a assay, which uses the endogenous phosphatidylinositol glycan, class A gene (Pig-a) as a reporter of mutation, has been developed as a method for evaluating in vivo mutagenicity. Pig-a gene mutation can be detected by identifying the presence of CD59, the glycosylphosphatidylinositol anchor protein, on the surface of erythrocytes (RBC Pig-a assay) and reticulocytes (PIGRET assay). The International Workshop on Genotoxicity Testing (IWGT) showed the usefulness of the RBC Pig-a assay through the evaluation of several compounds...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27931818/evaluation-of-the-pigret-assay-as-a-short-term-test-using-a-single-dose-of-diethylnitrosamine
#12
Kunio Wada, Risako Nishino, Tomoki Fukuyama, Kyomu Matsumoto
The PIGRET assay, which was developed as the Pig-a assay in reticulocytes, can detect mutagenicity of compounds earlier than the Pig-a assay in total red blood cells (RBC; RBC Pig-a assay). The usefulness of the PIGRET assay as a short-term test has been confirmed in a collaborative study in Japan with 24 chemicals. One of these chemicals, diethylnitrosamine (DEN), which mainly induces liver tumors in both sexes of rats, was tested. To determine the appropriate doses, DEN was dissolved in physiological saline and administered orally with a single dose to male 8-week-old Sprague-Dawley rats in a preliminary dose-range finding study...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27931814/pyrene-did-not-induce-gene-mutation-in-red-blood-cell-pig-a-assay-and-pigret-assay-in-rats
#13
Ikuma Yoshida, Akemi Matsumoto, Yumi Sakai, Yumiko Harada, Tsuneo Hashizume
A new in vivo gene mutation assay has been developed based on the phosphatidylinositol glycan anchor biosynthesis, Class A gene (Pig-a in rodents) as an endogenous reporter. Although a large number of chemicals have been evaluated in the rat Pig-a assay in 28-day repeat dose regimens, there was limited reporting of rat Pig-a assay after a single dose. A collaborative study by the Mammalian Mutagenicity Study group, which is a subgroup of the Japanese Environmental Mutagen Society, was conducted to verify the usefulness of the rat Pig-a assay after a single dose as a short-term genotoxicity test...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27910935/disentangling-the-roles-of-cholesterol-and-cd59-in-intermedilysin-pore-formation
#14
Courtney M Boyd, Edward S Parsons, Richard A G Smith, John M Seddon, Oscar Ces, Doryen Bubeck
The plasma membrane provides an essential barrier, shielding a cell from the pressures of its external environment. Pore-forming proteins, deployed by both hosts and pathogens alike, breach this barrier to lyse target cells. Intermedilysin is a cholesterol-dependent cytolysin that requires the human immune receptor CD59, in addition to cholesterol, to form giant β-barrel pores in host membranes. Here we integrate biochemical assays with electron microscopy and atomic force microscopy to distinguish the roles of these two receptors in mediating structural transitions of pore formation...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891564/a-homozygous-pign-missense-mutation-in-soft-coated-wheaten-terriers-with-a-canine-paroxysmal-dyskinesia
#15
Ana L Kolicheski, Gary S Johnson, Tendai Mhlanga-Mutangadura, Jeremy F Taylor, Robert D Schnabel, Taroh Kinoshita, Yoshiko Murakami, Dennis P O'Brien
Hereditary paroxysmal dyskinesias (PxD) are a heterogeneous group of movement disorders classified by frequency, duration, and triggers of the episodes. A young-adult onset canine PxD has segregated as an autosomal recessive trait in Soft-Coated Wheaten Terriers. The medical records and videos of episodes from 25 affected dogs were reviewed. The episodes of hyperkinesia and dystonia lasted from several minutes to several hours and could occur as often as >10/day. They were not associated with strenuous exercise or fasting but were sometimes triggered by excitement...
January 2017: Neurogenetics
https://www.readbyqxmd.com/read/27820950/the-ingenious-interactions-between-macrophages-and-functionally-plastic-retinal-pigment-epithelium-cells
#16
Takahiro Yamawaki, Eiko Ito, Atsushi Mukai, Morio Ueno, Jun Yamada, Chie Sotozono, Shigeru Kinoshita, Junji Hamuro
Purpose: The purpose of this study was to clarify the interactions between macrophages (MPs) and RPE cells in coculture systems to investigate the functional plasticity of RPE cells. Methods: Adherent peritoneal cells or murine MP cell line Raw 264.7 was cocultured with primary RPE cells taken from C57BL/6 mice, with or without lipopolysaccharide (LPS) or TNF-α stimulation. The cytokine levels of the culture supernatants (CSs) were then analyzed with the Bio-Plex murine 23-Plex Panel Assay Kit (Bio-Rad Laboratories)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27812245/paroxysmal-nocturnal-hemoglobinuria-from-bench-to-bed
#17
REVIEW
Amrallah A Mohammed, Hani El-Tanni, Tariq Al-Malki Atiah, Arwa Al-Malki Atiah, Marwan Al-Malki Atiah, Ayman A Rasmy
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia with highly variable clinical symptoms making the diagnosis and prediction of its outcome difficult. It is caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene that results in deficiency of the glycosylphosphatidylinositol anchor structure responsible for fixing a wide spectrum of proteins particularly CD55 and CD59. The clinical features of this disease arise as a result of complement-mediated hemolysis in unprotected red cells, leukocytes, and platelets as well as the release of free hemoglobin...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27780113/the-dysfunction-of-platelets-in-paroxysmal-nocturnal-hemoglobinuria
#18
Rong Fu, Yinping Meng, Yihao Wang, Hui Liu, Yi Liu, Lijuan Li, Shaoxue Ding, Guojin Wang, Jia Song, Zonghong Shao
INTRODUCTION: Thrombosis is a dangerous complication of paroxysmal nocturnal hemoglobinuria (PNH) and has a high mortality rate. However, the mechanism underlying the development of thrombosis in PNH remains unclear. To explore this, platelet function and serum complement activity were investigated in 14 patients with classical PNH, 11 with PNH aplastic anemia (AA) and 30 healthy controls. MATERIAL AND METHODS: Serum concentrations of the terminal complement complex (sC5b-9) were determined by enzyme-linked immunofluorescence assay (ELISA), and the levels of C5b-9, CD61 and CD62p on platelet membranes were determined by flow cytometry...
December 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27770464/in-vivo-pig-a-gene-mutation-assay-guidance-for-3rs-friendly-implementation
#19
Marian Raschke, Bernd-W Igl, Julia Kenny, Joanne Collins, Stephen D Dertinger, Carson Labash, Javed A Bhalli, Cameron C M Tebbe, Kylie M McNeil, Andreas Sutter
The rodent Pig-a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol-anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig-a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti-CD59 antibodies and flow cytometry. The Pig-a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal rodent 28-day general toxicology studies...
December 2016: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/27736290/antibodies-against-complement-regulatory-proteins-on-platelets-in-immune-thrombocytopenia
#20
Ursula Unterberger, Beate Eichelberger, Anja Ulz, Simon Panzer
In immune thrombocytopenia (ITP), antibodies reacting with platelet membrane glycoproteins (GP) mediate premature platelet cleavage, resulting in thrombocytopenia and therefore a risk of bleeding. These antibodies may induce complement activation, thus mediating complement-induced platelet destruction. In this study, we investigated the possibility of an additional complement-related pathogenic mechanism, where antibodies against the complement-regulatory factors CD55 and CD59 may directly interfere with normal complement function...
October 13, 2016: Platelets
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