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https://www.readbyqxmd.com/read/27910935/disentangling-the-roles-of-cholesterol-and-cd59-in-intermedilysin-pore-formation
#1
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
#2
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...
November 28, 2016: Neurogenetics
https://www.readbyqxmd.com/read/27820950/the-ingenious-interactions-between-macrophages-and-functionally-plastic-retinal-pigment-epithelium-cells
#3
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
#4
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
#5
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...
July 22, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27770464/in-vivo-pig-a-gene-mutation-assay-guidance-for-3rs-friendly-implementation
#6
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
#7
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
https://www.readbyqxmd.com/read/27729184/deficiency-of-the-complement-regulatory-protein-cd59-accelerates-the-development-of-diabetes-induced-atherosclerosis-in-mice
#8
Fengming Liu, Rupam Sahoo, Xiaowen Ge, Lin Wu, Pamela Ghosh, Xuebin Qin, Jose A Halperin
AIMS: Clinical and experimental evidence supports a strong link between the complement system, complement regulatory proteins and the pathogenesis of diabetes vascular complications. We previously reported that the complement regulatory protein CD59 is inactivated by glycation in humans with diabetes. Our objective for this study is to assess experimentally how the deficiency of CD59 impacts the development of diabetic atherosclerosis in vivo. METHODS: We crossed mCD59 sufficient and deficient mice into the ApoE(-/-) background to generate mCd59ab(+/+)/ApoE(-/-) and mCd59ab(-/-)/ApoE(-/-) mice, and induced diabetes by multiple low dose injections of streptozotocin...
August 28, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27725820/hide-and-seek-how-lyme-disease-spirochetes-overcome-complement-attack
#9
Peter Kraiczy
Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully survive in diverse host environments for a prolonged period of time. In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27725586/pathogenesis-of-paroxysmal-nocturnal-hemoglobinuria
#10
Yoshiko Murakami
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired GPI deficiency caused by somatic mutation of the PIGA gene in one or several hematopoietic stem cells. Recently, PNH caused by somatic mutation of one allele of the PIGT gene in combination with a germline mutation of the other allele was reported, showing that PIGA is not the only gene responsible for PNH, though other causes are rare. These mutant cells become GPI deficient, expand clonally and differentiate into all of the hematopoietic lineages. When GPI deficient erythrocytes increase in proportion, massive hemolysis occurs due to activated complement attack during infection...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27694521/mutations-in-the-phosphatidylinositol-glycan-c-pigc-gene-are-associated-with-epilepsy-and-intellectual-disability
#11
Simon Edvardson, Yoshiko Murakami, Thi Tuyet Mai Nguyen, Maher Shahrour, Anik St-Denis, Avraham Shaag, Nadira Damseh, Françoise Le Deist, Yenan Bryceson, Bassam Abu-Libdeh, Philippe M Campeau, Taroh Kinoshita, Orly Elpeleg
BACKGROUND: Of our 1400 exome-studied patients, 67% originate from consanguineous families. ∼80% suffer from variable degree of intellectual disability (ID). The search for disease causing genes using homozygosity mapping was progressing slowly until 2010, then markedly accelerated by the introduction of exome analysis. OBJECTIVES: To identify the disease causing mutation(s) in three patients from two unrelated families who suffered from global developmental delay, severe ID and drug-responsive seizure disorder...
September 30, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27693177/correlation-between-cellular-expression-of-complement-regulatory-proteins-with-depletion-and-repopulation-of-b-lymphocytes-in-peripheral-blood-of-patients-with-rheumatoid-arthritis-treated-with-rituximab
#12
Daniela Viecceli, Mariana Pires Garcia, Laiana Schneider, Ana Paula Alegretti, Cristiano Kohler Silva, André Lucas Ribeiro, Claiton Viegas Brenol, Ricardo Machado Xavier
OBJECTIVES: To correlate the basal expression of complement regulatory proteins (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with depletion and time repopulation of such cells. METHODS: Ten patients with RA received two infusions of 1g of RTX with an interval of 14 days. Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B-lymphocytes was carried out immediately before the first infusion...
September 17, 2016: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/27688119/tongue-sole-cynoglossus-semilaevis-cd59-a-complement-inhibitor-that-binds-bacterial-cells-and-promotes-bacterial-escape-from-the-killing-of-fish-serum
#13
Zhi-Hai Sui, Mo-Fei Li, Li Sun
CD59 is a complement regulatory protein that inhibits the formation of membrane attack complex of complement. In this study, we examined the expression and activity of tongue sole (Cynoglossus semilaevis) CD59 (CsCD59). CsCD59 possesses the conserved structural features of CD59 and shares 33%-46% sequence identities with other fish CD59. Expression of CsCD59 was high in liver, spleen, and muscle, and was stimulated by infection of bacterial pathogens. Recombinant CsCD59 (rCsCD59) exhibited an apparent inhibition effect on the activation of tongue sole serum complement...
September 26, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27667587/expression-pattern-of-cd55-and-cd59-on-red-blood-cells-in-sickle-cell-disease
#14
Lama Al-Faris, Monera Al-Rukhayes, Salah Al-Humood
OBJECTIVES: To investigate the pattern of CD55 and CD59 expression on RBCs of SCD patients, and its association with anemia, biochemical parameters of hemolysis, level of erythropoietin, and pro-inflammatory markers. METHODS: Flow cytometric analysis was performed on RBCs from 71 adult SCD patients and 53 healthy controls, using the commercial REDQUANT kit. RESULTS: CD59 deficiency was significantly higher among SCD patients than among healthy controls...
September 25, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27638160/isolation-of-autologous-adipose-tissue-derived-mesenchymal-stem-cells-for-bone-repair
#15
E Raposio, S Bonomini, F Calderazzi
INTRODUCTION: Adipose tissue represents an abundant and accessible source of adult stem cells that can differentiate into cells and tissues of mesodermal origin, including osteogenic cells. METHODS: This paper describes the procedure to obtain a 5-cm(3) saline sample, containing the adipose-derived stem cells (ASCs) pellet, starting from lipoaspirate obtained from a conventional abdominal liposuction. RESULTS: A mean of 2.5×10(6) cells is isolated for each procedure; 35% (875000) of these are CD34+/CD45- cells, which express a subset of both positive (CD10, CD13, CD44, CD59, CD73, CD90, HLAABC) and negative (CD33, CD39, CD102, CD106, CD146, HLADR) cell-associated surface antigens, characterizing them as ASCs...
September 13, 2016: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/27637482/monitoring-genotoxicity-in-patients-receiving-chemotherapy-for-cancer-application-of-the-pig-a-assay
#16
Katsuyoshi Horibata, Akiko Ukai, Shigeo Ishikawa, Ayako Sugano, Masamitsu Honma
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
https://www.readbyqxmd.com/read/27590276/a-strategy-to-ensure-safety-of-stem-cell-derived-retinal-pigment-epithelium-cells
#17
Parul Choudhary, Paul John Whiting
Cell replacement and regenerative therapy using embryonic stem cell-derived material holds promise for the treatment of several pathologies. However, the safety of this approach is of prime importance given the teratogenic potential of residual stem cells, if present in the differentiated cell product. Using the example of embryonic stem cell-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration, we present a novel strategy for ensuring the absence of stem cells in the RPE population...
September 2, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27588825/role-of-igm-and-angiotensin-ii-type-i-receptor-autoantibodies-in-local-complement-activation-in-placental-ischemia-induced-hypertension-in-the-rat
#18
Jean F Regal, Megan E Strehlke, Jenna M Peterson, Cameron R Wing, Jordan E Parker, Noel Fernando Nieto, Lynne T Bemis, Jeffrey S Gilbert, Sherry D Fleming
Preeclampsia is characterized by development of hypertension during pregnancy and reduced placental perfusion. Previous studies in a rat model of placental ischemia-induced hypertension demonstrated that inhibiting complement activation attenuated increased maternal blood pressure with C3a and C5a identified as the important products of complement activation. Given that in other forms of ischemia both natural IgM and antigen antibody complexes initiate complement activation, we hypothesized that placental ischemia exposes neoepitopes recognized by IgM to cause local complement activation and hypertension...
October 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27581231/a-population-study-using-the-human-erythrocyte-pig-a-assay
#19
Yiyi Cao, Li Yang, Nannan Feng, Oumin Shi, Jing Xi, Xinyue You, Chunrong Yin, Huan Yang, Katsuyoshi Horibata, Masamitsu Honma, Biyun Qian, Wei Weng, Yang Luan
Erythrocyte-based PIG-A assay is sensitive and reliable in detecting exposure to mutagenetic agents in animal studies, but there are few data from human populations. In this study, we employed a method for detecting CD59 phenotypic variants, resulting from mutation in the PIG-A gene, in human red blood cells (RBCs), and determined the CD59-deficient RBC (RBC(CD59-) ) frequencies in 217 subjects from general population. The majority of subjects had a relatively low mutant frequencies (MFs) (average, 5.25 ± 3...
October 2016: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/27568864/therapy-with-eculizumab-for-patients-with-cd59-p-cys89tyr-mutation
#20
Dror Mevorach, Inna Reiner, Amir Grau, Uri Ilan, Yackov Berkun, Asaf Ta-Shma, Orly Elpeleg, Zamir Shorer, Simon Edvardson, Adi Tabib
OBJECTIVE: The objective of this work was to report on the outcome of eculizumab treatment in pediatric patients with recurrent acute predominantly motor, demyelinating neuropathy with conduction block, and chronic hemolysis attributed to p.Cys89Tyr mutation in the CD59 gene. METHODS: Four patients were recruited from our new registry of patients with homozygosity for the p.Cys89Tyr mutation on CD59. Participants received repeated intravenous eculizumab. In this 24-month open-label phase IIa study, we aimed to determine whether eculizumab reduces chronic hemolysis, and cumulative doses of steroids and intravenous immunoglobulin (IVIG), and ameliorates neurological deficits, compared to pretreatment status...
August 29, 2016: Annals of Neurology
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