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https://www.readbyqxmd.com/read/29678656/complement-mediated-activation-of-the-nlrp3-inflammasome-and-its-inhibition-by-aav-mediated-delivery-of-cd59-in-a-model-of-uveitis
#1
Binit Kumar, Siobhan M Cashman, Rajendra Kumar-Singh
Uveitis is an inflammatory disorder of the eye responsible for approximately 10%-15% of blindness in the US. In this study, we examined the role of the complement membrane attack complex (MAC) and the NLRP3 inflammasome in the pathogenesis of experimental autoimmune uveitis (EAU) in normal and C9-/- mice that are incapable of assembling the MAC. We discovered that the MAC and the NLRP3 inflammasome and associated production of IL-1β are elevated in EAU mice and that MAC may be involved in regulation of Th1 and Th17 cell differentiation...
March 19, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29643245/recombinant-porcine-reproductive-and-respiratory-syndrome-virus-expressing-membrane-bound-il-15-as-immunomodulatory-adjuvant-enhances-nk-and-%C3%AE-%C3%AE-t-cell-responses-and-confers-heterologous-protection
#2
Qian M Cao, Yan-Yan Ni, Dianjun Cao, Debin Tian, Danielle M Yugo, C Lynn Heffron, Christopher Overend, Sakthivel Subramaniam, Adam J Rogers, Nicholas Catanzaro, Tanya LeRoith, Paul C Roberts, Xiang-Jin Meng
Cytokines are often used as adjuvants to improve vaccine immunogenicity, since they are important in initiating and shaping the immune response. The available commercial modified live-attenuated vaccines (MLVs) against porcine reproductive and respiratory syndrome virus (PRRSV) are unable to mount sufficient heterologous protection, as they typically induce weak innate and inadequate T cell responses. In this study, we investigated the immunogenicity and vaccine efficacy of recombinant PRRSV MLVs incorporated with porcine cytokine IL-15 or IL-18 gene fusing to a glycophosphatidylinositol (GPI) modification signal that can anchor the cytokines to cell membrane...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29595916/the-complement-system-in-hypertension-and-renal-damage-in-the-dahl-ss-rat
#3
Jean F Regal, Connor F Laule, Luke McCutcheon, Kate M Root, Hayley Lund, Shireen Hashmat, David L Mattson
Evidence indicates the immune system is important in development of hypertension and kidney disease. In the Dahl Salt-Sensitive (SS) rat model, lymphocytes play a role in development of hypertension and kidney damage after increased sodium intake. Recent transcriptomic analyses demonstrate upregulation of the innate immune complement system in the kidney of Dahl SS rat fed a high-salt diet, leading us to hypothesize that inhibition of complement activation would attenuate development of hypertension and kidney damage...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29581232/distinct-cargo-specific-response-landscapes-underpin-the-complex-and-nuanced-role-of-galectin-glycan-interactions-in-clathrin-independent-endocytosis
#4
Mohit P Mathew, Julie G Donaldson
Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting from the outside, could be a part of that endocytic machinery. We show that the perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects CIE. Interestingly, these changes in glycosylation had cargo-specific effects. For example, in HeLa cells, N-acetylglucosamine treatment, which increases glycan branching, increased major histocompatibility complex class I (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule (CD59)...
March 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29541246/a-role-for-gpi-cd59-in-promoting-t-cell-signal-transduction-via-lat
#5
Li-Na Wang, Mei-Hua Gao, Bing Wang, Bei-Bei Cong, Shu-Chao Zhang
Cluster of differentiation 59 (CD59) is a glycosylphosphatidylinositol-anchored protein. Cross-linking of CD59 with specific monoclonal antibodies can cause a series of intracellular signal transduction events. However, the underlying molecular mechanisms are poorly understood. Linker for activation of T-cells (LAT) is a crucial adaptor protein in T-cell signaling, and its phosphorylation and palmitoylation are essential for its localization and function. In a previous study by the present authors, it was demonstrated that CD59 may be responsible for LAT palmitoylation, thereby regulating T-cell signal transduction...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29521526/cd59-a-promising-target-for-tumor-immunotherapy
#6
Ronghua Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
CD59 has been identified as a glycosylphosphatidylinositol-anchored membrane protein that acts as an inhibitor of the formation of the membrane attack complex to regulate complement activation. Recent studies have shown that CD59 is highly expressed in several cancer cell lines and tumor tissues. CD59 also regulates the function, infiltration and phenotypes of a variety of immune cells in the tumor microenvironment. Herein, we summarized recent advances related to the functions and mechanisms of CD59 in the tumor microenvironment...
March 9, 2018: Future Oncology
https://www.readbyqxmd.com/read/29504353/a-case-of-thrombosis-due-to-paroxysmal-nocturnal-haemoglobinuria-presenting-at-an-early-age
#7
Qurrat Ul Ain, Huzaifa Saleem, Sarwat Iqbal, Rabia Ghayas
Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired, rare life-threatening disorder characterised by compliment mediated hemolytic anemia, thrombosis and impaired bone marrow function. It occasionally presents in childhood or adolescence. This is a case of a 14-year old female presented with complaints of shortness of breath, palpitation and abdominal pain whose laboratory test results were consistent with Coomb's test negative haemolytic anaemia. Contrast enhanced Computed Tomography Scan (CT scan) of abdomen revealed splanchnic circulation thrombosis as well as partially occluding thrombus in the inferior vena cava...
January 2018: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/29486674/renal-involvement-in-paroxysmal-nocturnal-hemoglobinuria-an-update-on-clinical-features-pathophysiology-and-treatment
#8
Styliani I Kokoris, Eleni Gavriilaki, Aggeliki Miari, Αnthi Travlou, Elias Kyriakou, Achilles Anagnostopoulos, Elissavet Grouzi
OBJECTIVES: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment. METHODS: A thorough PubMed search was performed using as main keywords: 'paroxysmal nocturnal hemoglobinuria', 'acute kidney injury', 'chronic kidney disease' and 'eculizumab'. RESULTS: PNH's etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease's major clinical features, like intravascular hemolysis, cytopenias and thrombosis...
February 28, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29476661/epigenomic-signature-of-adrenoleukodystrophy-predicts-compromised-oligodendrocyte-differentiation
#9
Agatha Schlüter, Juan Sandoval, Stéphane Fourcade, Angel Díaz-Lagares, Montserrat Ruiz, Patrizia Casaccia, Manel Esteller, Aurora Pujol
Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids...
February 24, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29467851/proteinase-3-expression-on-the-neutrophils-of-patients-with-paroxysmal-nocturnal-hemoglobinuria
#10
Hui Liu, Yi Liu, Yi Li, Zhaoyun Liu, Liyan Li, Shaoxue Ding, Yihao Wang, Tian Zhang, Lijuan Li, Zonghong Shao, Rong Fu
Proteinase 3 (PR3) is released from neutrophils and regulates platelet activity, which is associated with cluster of differentiation (CD)177 antigen (NB1), a glycosylphosphatidylinositol-linked protein. In the present study, the effect of PR3 on thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) and PNH-aplastic anemia (AA) syndrome was explored. The expression of PR3 and NB1 on CD59- neutrophils was detected by flow cytometry, immunofluorescence (IF), reverse transcription-quantitative polymerase chain reaction analysis and western blotting...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29466390/the-role-of-complement-activation-in-rhabdomyolysis-induced-acute-kidney-injury
#11
XuDong Huang, Wei Zhao, LiXia Zhang, XinJun Yang, LiHui Wang, YunShuang Chen, JingHua Wang, Chao Zhang, GuangLi Wu
Rhabdomyolysis (RM) may cause kidney damage and results primarily in acute kidney injury (AKI). Complement is implicated in the pathogenesis of renal diseases and ischemia-reperfusion injury (IRI), but the role of complement, especially its activation pathway(s) and its effect in RM-induced AKI, is not clear. This study established a rat model of AKI induced by RM via intramuscular treatment with glycerol. Cobra venom factor (CVF) was administered via tail vein injection to deplete complement 12 h prior to intramuscular injection of glycerol...
2018: PloS One
https://www.readbyqxmd.com/read/29447841/crispr-cas9-generated-human-cd46-cd55-and-cd59-knockout-cell-lines-as-a-tool-for-complement-research
#12
Astrid J F Thielen, Iris M van Baarsen, Marlieke L Jongsma, Sacha Zeerleder, Robbert M Spaapen, Diana Wouters
BACKGROUND: To prevent unwanted complement activation and subsequent damage, complement activation must be tightly regulated on healthy host cells. Dysregulation of the complement system contributes to the pathology of diseases like Paroxysmal Nocturnal Hemoglobinuria and atypical Hemolytic Uremic Syndrome. To investigate complement regulator deficiencies, primary patient cells may be used, but access to patient cells may be limited and cells are heterogeneous between different patients...
February 12, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29421990/measurement-of-soluble-cd59-in-csf-in-demyelinating-disease-evidence-for-an-intrathecal-source-of-soluble-cd59
#13
Wioleta M Zelek, Lewis M Watkins, Owain W Howell, Rhian Evans, Sam Loveless, Neil P Robertson, Marijke Beenes, Loek Willems, Ricardo Brandwijk, B Paul Morgan
BACKGROUND: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). OBJECTIVES: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated...
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29406582/high-complement-levels-in-astrocyte-derived-exosomes-of-alzheimer-disease
#14
Edward J Goetzl, Janice B Schwartz, Erin L Abner, Gregory A Jicha, Dimitrios Kapogiannis
OBJECTIVE: Astrocytes fulfill neuronal trophic roles normally, but are transformed in Alzheimer disease (AD) into A1-type reactive astrocytes that may destroy neurons through unknown mechanisms. METHODS: To investigate astrocyte inflammatory mechanisms, astrocyte-derived exosomes (ADEs) were isolated immunochemically from plasma samples of AD patients and matched controls for enzyme-linked immunosorbent assay quantification of complement proteins. RESULTS: ADE levels of C1q, C4b, C3d, factor B, factor D, Bb, C3b, and C5b-C9 terminal complement complex, but not mannose-binding lectin, normalized by the CD81 exosome marker were significantly higher for AD patients (n = 28) than age- and gender-matched controls (all p < 0...
February 6, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29355143/value-of-cd16-cd66b-cd45-in-comparison-to-cd55-cd59-cd45-in-diagnosis-of-paroxysmal-nocturnal-haemoglobinuria-an-indian-experience
#15
Mrinalini Kotru, Rahul Sharma, Suman Kumar Pramanik, Abhishek Purohit, Gurmeet Singh, Avinash Kumar Singh, Deepti Muterja, Pravas Mishra, Tulika Seth, Seema Tyagi, Manoranjan Mahapatra, Hara Prasad Pati, Renu Saxena
BACKGROUND & OBJECTIVES: Diagnosis of paroxysmal nocturnal haemoglobinuria (PNH), a rare haematopoietic stem cell disorder, is challenging in patients with bone marrow failure (BMF) syndrome like aplastic anaemia (AA). This study was conducted with the aim to test the efficacy of the newly recommended markers viz. anti-CD16 and CD66b antibody over the existing anti-CD55 and CD59 antibody for PNH diagnosis in India. METHODS: This study was conducted on 193 suspected cases of PNH by flow cytometry using lyse wash technique to stain the granulocytes with CD16/CD66b and CD55/CD59...
September 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29338788/high-throughput-immunophenotypic-characterization-of-bone-marrow-and-cord-blood-derived-mesenchymal-stromal-cells-reveals-common-and-differentially-expressed-markers-identification-of-angiotensin-converting-enzyme-cd143-as-a-marker-differentially-expressed
#16
Eliana Amati, Omar Perbellini, Gianluca Rotta, Martina Bernardi, Katia Chieregato, Sabrina Sella, Francesco Rodeghiero, Marco Ruggeri, Giuseppe Astori
BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking...
January 16, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29306438/revealing-the-raft-domain-organization-in-the-plasma-membrane-by-single-molecule-imaging-of-fluorescent-ganglioside-analogs
#17
Kenichi G N Suzuki, Hiromune Ando, Naoko Komura, Miku Konishi, Akihiro Imamura, Hideharu Ishida, Makoto Kiso, Takahiro K Fujiwara, Akihiro Kusumi
Gangliosides have been implicated in a variety of physiological processes, particularly in the formation and function of raft domains in the plasma membrane. However, the scarcity of suitable fluorescent ganglioside analogs had long prevented us from determining exactly how gangliosides perform their functions in the live-cell plasma membrane. With the development of new fluorescent ganglioside analogs, as described by Komura et al. (2017), this barrier has been broken. We can now address the dynamic behaviors of gangliosides in the live-cell plasma membrane, using fluorescence microscopy, particularly by single-fluorescent molecule imaging and tracking...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29306055/trimethoprim-sulfamethoxazole-treatment-increases-the-pig-a-mutant-frequency-in-peripheral-blood-from-severely-malnourished-rats
#18
M Monserrat Pacheco-Martínez, Elsa Cervantes-Ríos, María Del Carmen García-Rodríguez, Rocío Ortiz-Muñiz
Severe malnutrition is a complex condition that increases susceptibility to infections. Thus, drugs are extensively used in malnutrition cases. In the present study, we assessed the mutagenic effects of combined trimethoprim and sulfamethoxazole (TMP-SMX) treatment in undernourished (UN) and well-nourished (WN) rats. Six-week-old UN and WN Han-Wistar rats were treated with TMP-SMX at a daily dose of 10 mg/kg/d TMP and 50 mg/kg/d SMX for 5 or 10 days. Blood was collected from the tail vein one day before (day -1) and 15, 30, and 45 days after TMP-SMX administration...
January 2018: Mutation Research
https://www.readbyqxmd.com/read/29296844/potential-impact-of-complement-regulator-deficiencies-on-hemolytic-reactions-due-to-minor-abo-mismatched-transfusions
#19
Priyanka Pandey, Waseem Q Anani, Jerome L Gottschall, Gregory A Denomme
Minor ABO-mismatched transfusions are a common occurrence, although infrequent transfusion reactions occur. We sought to investigate the regulation of complement C3 activation induced by anti-A. In vitro complement C3 activation was observed with 10 of 30 group O samples and correlated with immunoglobulin M (IgM) anti-A titers. We developed an in vitro paroxysmal nocturnal hemoglobinuria (PNH) model of hemolysis in which group A1 red blood cells (RBCs) were chemically treated with 2-aminoethylisothiouronium (AET) to alter regulators of complement C3 activation...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29237063/spectrum-of-pig-a-mutations-in-t-lymphocytes-of-rats-treated-with-procarbazine
#20
Javier Revollo, Javed A Bhalli, Cameron Tebbe, Jessica Noteboom, Demetria Thomas, Page McKinzie, Nicholas Felton, Mason G Pearce, Vasily N Dobrovolsky
Procarbazine is a primary component of antineoplastic combination chemotherapy often used for the treatment of Hodgkin's lymphoma. It is believed that cytostatic and cytotoxic properties of procarbazine are mediated via its interaction with genomic DNA. Procarbazine is a carcinogen in animal models; it is classified as Group 2A compound by IARC. Also it is known as an in vitro and in vivo mutagen and genotoxicant. However, the molecular mechanism by which procarbazine induces mutations is not thoroughly understood and the spectrum of procarbazine-induced in vivo mutations is described insufficiently...
December 8, 2017: Mutagenesis
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