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https://www.readbyqxmd.com/read/28734966/development-of-new-ganglioside-probes-and-unraveling-of-raft-domain-structure-by-single-molecule-imaging
#1
REVIEW
Kenichi G N Suzuki, Hiromune Ando, Naoko Komura, Takahiro Fujiwara, Makoto Kiso, Akihiro Kusumi
Gangliosides are involved in a variety of biological roles and are a component of lipid rafts found in cell plasma membranes (PMs). Gangliosides are especially abundant in neuronal PMs and are essential to their physiological functions. However, the dynamic behaviors of gangliosides have not been investigated in living cells due to a lack of fluorescent probes that behave like their parental molecules. We have recently developed, using an entirely chemical method, four new ganglioside probes (GM1, GM2, GM3, and GD1b) that act similarly to their parental molecules in terms of raft partitioning and binding affinity...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28718265/haemoglobinuria-and-portal-venous-thrombosis-in-a-young-male
#2
Zain Ul Abideen, Munnam Sohail Jafar, Nasir Hameed, Ahmad Malik
Paroxysmal nocturnal haemoglobinuria is a non-malignant stem cell disorder due to acquired somatic mutations in cell surface anchored proteins CD55 and CD59. Both have a compliment inhibitory role and their deficiency leads to intravascular haemolysis. This paper reports a challenging case of a 25 years old male who presented with generalized weakness, exertional dyspnoea and episodic early morning haematuria. Recently, he started developing progressive abdominal distention and dull generalized abdominal pain...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28714084/applying-the-erythrocyte-pig-a-assay-concept-to-rat-epididymal-sperm-for-germ-cell-mutagenicity-evaluation
#3
Zhiying Ji, Matthew J LeBaron
The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry...
July 17, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28680334/expression-of-cd55-cd59-and-cd35-on-red-blood-cells-of-%C3%AE-thalassaemia-patients
#4
Ayşegül Uǧur Kurtoǧllu, Belkls Koçtekin, Erdal Kurtoǧlu, Mustafa Yildiz, Selen Bozkurt
AIM OF THE STUDY: β-thalassaemia (β-Thal) is considered a severe, progressive haemolytic anaemia, which needs regular blood transfusions for life expectancy. Complement-mediated erythrocyte destruction can cause both intravascular and extravascular haemolysis. Complement regulatory proteins protect cells from such effects of the complement system. We aimed to perform quantitative analysis of membrane-bound complement regulators, CD55 (decay accelerating factor - DAF), CD35 (complement receptor type 1 - CR1), and CD59 (membrane attack complex inhibitory factor - MACIF) on peripheral red blood cells by flow cytometry...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28658265/enhanced-cdc-of-b-cell-chronic-lymphocytic-leukemia-cells-mediated-by-rituximab-combined-with-a-novel-anti-complement-factor-h-antibody
#5
Mark T Winkler, Ryan T Bushey, Elizabeth B Gottlin, Michael J Campa, Eross S Guadalupe, Alicia D Volkheimer, J Brice Weinberg, Edward F Patz
Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody...
2017: PloS One
https://www.readbyqxmd.com/read/28629435/eculizumab-treatment-stochastic-occurrence-of-c3-binding-to-individual-pnh-erythrocytes
#6
Michela Sica, Tommaso Rondelli, Patrizia Ricci, Maria De Angioletti, Antonio M Risitano, Rosario Notaro
BACKGROUND: C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding. METHODS: To investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28622911/demyelination-strokes-and-eculizumab-lessons-from-the-congenital-cd59-gene-mutations
#7
Adi Tabib, Netanel Karbian, Dror Mevorach
Neurological symptoms of patients with p.Cys89Tyr mutation in the CD59 gene include recurrent peripheral neuropathy resembling Guillain-Barré syndrome, characterized by sensory-motor demyelinating neuropathy with secondary axonal damage and moderate enhancement of the nerve roots on spine MRI, together with recurrent strokes and retinal involvement. Three additional mutations in CD59, leading to loss of function, have been described, and overall, 12/12 (100%) of patients with any mutation presented with neurological symptoms; 11/12 (92%) patients presented with recurrent peripheral neuropathy, 6/12 (50%) with recurrent strokes, and 1/12 (8%) with retinal involvement...
June 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28620953/molecular-characterisation-of-%C3%AE-and-%C3%AE-thalassaemia-among-indigenous-senoi-orang-asli-communities-in-peninsular-malaysia
#8
Danny Xuan Rong Koh, Raja Zahratul Azma Raja Sabudin, Malisa Mohd Yusoff, Noor Hamidah Hussin, Rahimah Ahmad, Ainoon Othman, Endom Ismail
Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn)...
June 16, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28612574/-optimization-ofpig-agene-mutation-in-rats-and-assessment-of-time-dependent-and-dose-response-relationship-of-n-ethyl-n-nitrosourea
#9
Si-Jia Ma, Jiao Huo, Jin-Yao Chen, Qi-Yan Chen, Li-Shi Zhang
OBJECTIVES: To optimize the method of Pig-a mutation assay, and to explore the time-dependent and dose-response relationship of N-ethyl-N-nitrosourea (ENU). METHODS: Thirty rats were randomly assigned to 5 groups: treated with PBS (control group)or different doses of ENU (10, 20, 40 and 80 mg/kg) for 3 d by oral gavage. Blood samples were collected at 0 d, 15 d, 30 d, 45 d, 60 d, 75 d and 90 d. After enrichment, erythrocytes were incubated with Anti-CD59-APC and SYTO 13 nucleic acid dye solution...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28574201/standardized-high-sensitivity-flow-cytometry-testing-for-paroxysmal-nocturnal-hemoglobinuria-in-children-with-acquired-bone-marrow-failure-disorders-a-single-center-us-study
#10
Rachel E Donohue, Andrea N Marcogliese, Ghadir S Sasa, M Tarek Elghetany, Alka A Redkar, Alison A Bertuch, Choladda V Curry
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder that has not been well-documented in children, particularly those with acquired bone marrow failure disorders (ABMFD)-acquired aplastic anemia (AAA) and myelodysplastic syndrome (MDS). Therefore, we sought to determine the prevalence of PNH populations in children with ABMFD. METHODS: PNH testing was performed in children with an ABMFD diagnosis using high sensitivity (≥0...
June 2, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28551767/does-rarity-mean-imparity-biological-characteristics-of-osteosarcoma-cells-originating-from-the-spine
#11
Zhenhua Zhou, Yan Li, Xu Yan, Xudong Wang, Cheng Yang, Haifeng Wei, Xinghai Yang, Jianru Xiao
PURPOSE: Osteosarcoma is one of the most common malignancies in bones and is often found in limbs. Until now, it is not clear why osteosarcoma is rare in the spine. On the other hand, previous biological characteristics study about osteosarcoma of spine was also rare because of its low incidence. To explore the biology of spinal osteosarcoma, a stable osteosarcoma cell line derived from spine is necessary. METHODS: A novel osteosarcoma cell line named NEO217 was established from spinal osteosarcoma tissues obtained from a Chinese male patient...
May 27, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28545132/proteomics-investigation-of-oscc-specific-salivary-biomarkers-in-a-hungarian-population-highlights-the-importance-of-identification-of-population-tailored-biomarkers
#12
Éva Csősz, Péter Lábiscsák, Gergő Kalló, Bernadett Márkus, Miklós Emri, Adrienn Szabó, Ildikó Tar, József Tőzsér, Csongor Kiss, Ildikó Márton
Oral squamous cell carcinoma (OSCC) accounting for about 90% of malignant oral lesions is the 6th most common malignancy worldwide. Diagnostic delay may contribute to dismal survival rate therefore, there is a need for developing specific and sensitive biomarkers to improve early detection. Hungarian population occupies the top places of statistics regarding OSCC incidence and mortality figures therefore, we aimed at finding potential salivary protein biomarkers suitable for the Hungarian population. In this study we investigated 14 proteins which were previously reported as significantly elevated in saliva of patients with OSCC...
2017: PloS One
https://www.readbyqxmd.com/read/28542228/alteration-of-membrane-complement-regulators-is-associated-with-transporter-status-in-patients-on-peritoneal-dialysis
#13
Daniel Kitterer, Dagmar Biegger, Stephan Segerer, Niko Braun, M Dominik Alscher, Joerg Latus
INTRODUCTION: A growing body of evidence from animal models and cell culture studies indicate an important role of a local regulatory complement system (CS) in peritoneal injury during peritoneal dialysis (PD). We investigated the expression of the local regulatory CS (reflected by CD46,CD55,CD59) in the peritoneal tissue of patients with different membrane function characteristics. PATIENTS AND METHODS: Biopsies from the parietal peritoneum were taken from 24 patients on PD, 22 uremic patients prior to PD...
2017: PloS One
https://www.readbyqxmd.com/read/28534443/cd59-polymorphisms-are-associated-with-gene-expression-and-different-sexual-susceptibility-to-pemphigus-foliaceus
#14
Amanda Salviano-Silva, Maria Luiza Petzl-Erler, Angelica Beate Winter Boldt
Pemphigus foliaceus (PF) is an autoimmune disease, endemic in Brazilian rural areas, characterized by acantholysis and accompanied by complement activation, with generalized or localized distribution of painful epidermal blisters. CD59 is an essential complement regulator, inhibiting formation of the membrane attack complex, and mediating signal transduction and activation of T lymphocytes. CD59 has different transcripts by alternative splicing, of which only two are widely expressed, suggesting the presence of regulatory sites in their noncoding regions...
May 23, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28533125/markers-of-immune-mediated-inflammation-in-the-brains-of-young-adults-and-adolescents-with-type-1-diabetes-and-fatal-diabetic-ketoacidosis-is-there-a-difference
#15
William H Hoffman, Carol M Artlett, Dallas Boodhoo, Mary G F Gilliland, Luis Ortiz, Dries Mulder, David H T Tjan, Alvaro Martin, Alexandru Tatomir, Horea Rus
Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0...
May 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28518050/acetylcholinesterase-provides-new-insights-into-red-blood-cell-ageing-in-vivo-and-in-vitro
#16
Joames K Freitas Leal, Merel J W Adjobo-Hermans, Roland Brock, Giel J C G M Bosman
BACKGROUND: During its 120 days sojourn in the circulation, the red blood cell (RBC) remodels its membrane. Acetylcholinesterase (AChE) is a glycosylphosphatidylinositol (GPI)-linked enzyme that may serve as a marker for membrane processes occurring this ageing-associated remodelling process. MATERIALS AND METHODS: Expression and enzymatic activity of AChE were determined on RBCs of various ages, as obtained by separation based on volume and density (ageing in vivo), and on RBCs of various times of storage in blood bank conditions (ageing in vitro), as well as on RBC-derived vesicles...
May 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28516949/paroxysmal-nocturnal-haemoglobinuria
#17
REVIEW
Anita Hill, Amy E DeZern, Taroh Kinoshita, Robert A Brodsky
Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors...
May 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28500075/overexpression-of-human-cd55-and-cd59-or-treatment-with-human-cd55-protects-against-renal-ischemia-reperfusion-injury-in-mice
#18
Anjan K Bongoni, Bo Lu, Evelyn J Salvaris, Veena Roberts, Doreen Fang, Jennifer L McRae, Nella Fisicaro, Karen M Dwyer, Peter J Cowan
Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of increasing CD55 and CD59 activity has not been examined. In this study, we investigated the impact of overexpression of human (h) CD55 ± hCD59 or treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm renal ischemia, and analyzed 24 h after reperfusion for renal function (serum creatinine and urea), complement deposition (C3b/c and C9), and infiltration of neutrophils and macrophages...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28484166/molecular-genetics-biochemistry-and-biology-of-pnh
#19
Taroh Kinoshita
Paroxysmal nocturnal hemoglobinuria (PNH) manifests by clonal expansion of mutant hematopoietic stem cells (HSCs) bearing a somatic mutation in the X-linked PIGA gene. PIGA mutations cause defective biosynthesis of GPI and cell surface deficiency of GPI-anchored proteins such as DAF and CD59, leading to intravascular hemolysis and thrombosis. These two major symptoms of PNH can be controlled by eculizumab, an anti-C5 monoclonal antibody. Bone marrow failure, the third major symptom of PNH, is autoimmune-mediated and contributes to the clonal expansion of GPI-defective HSCs by selectively attacking GPI-positive wild-type HSCs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28476858/mutating-a-conserved-cysteine-in-gpihbp1-reduces-amounts-of-gpihbp1-in-capillaries-and-abolishes-lpl-binding
#20
Christopher M Allan, Cris J Jung, Mikael Larsson, Patrick J Heizer, Yiping Tu, Norma P Sandoval, Tiffany Ly P Dang, Rachel S Jung, Anne P Beigneux, Pieter J de Jong, Loren G Fong, Stephen G Young
Mutation of conserved cysteines in proteins of the Ly6 family cause human disease-chylomicronemia in the case of glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1) and paroxysmal nocturnal hemoglobinuria in the case of CD59. A mutation in a conserved cysteine in CD59 prevented the protein from reaching the surface of blood cells. In contrast, mutation of conserved cysteines in human GPIHBP1 had little effect on GPIHBP1 trafficking to the surface of cultured CHO cells. The latter findings were somewhat surprising and raised questions about whether CHO cell studies accurately model the fate of mutant GPIHBP1 proteins in vivo...
July 2017: Journal of Lipid Research
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