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https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#1
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28292372/clinico-haematological-features-of-paroxysmal-nocturnal-haemoglobinuria
#2
Maria Khan, Saqib Qayyum Ahmad, Mukarram Bashir, Parvez Ahmed, Muhammad Ayyub
The aim of this study was to determine the frequency of various clinico-haematological features in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). It was an observational study carried out from October 2008 - January 2016. All the patients of PNH, diagnosed on the basis of clinical and laboratory findings and confirmed by CD55 and CD59 deficiency on red cells by means of flow cytometry, were included in the study. A total of 22 patients were diagnosed which included 18 (81.8%) males and 4 (18...
January 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
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
#3
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/28104671/lack-of-association-of-cd55-receptor-genetic-variants-and-severe-malaria-in-ghanaian-children
#4
Kathrin Schuldt, Christa Ehmen, Juergen Sievertsen, Jennifer Evans, Juergen May, Daniel Ansong, Birgit Muntau, Gerd Ruge, Christian Timmann, Tsiri Agbenyega, Rolf D Horstmann, Thorsten Thye
In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes...
March 10, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#5
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/28008159/a-common-cd55-rs2564978-variant-is-associated-with-the-susceptibility-of-non-small-cell-lung-cancer
#6
Yanyan Zhang, Zhi Zhang, Lei Cao, Jia Lin, Zhenbang Yang, Xuemei Zhang
CD55, as one of key membrane-bound complement-regulatory proteins (mCRPs), is crucial for the progression of various cancers. This study aims to investigate the role of CD55 variants in the development of non-small cell lung cancer (NSCLC). A case-control study, including 706 lung cancer cases and 706 health controls, was conducted in a Chinese population. The odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression. We found that significantly higher lung cancer risk was linked with CD55 rs2564978 CC genotype (OR = 1...
January 24, 2017: Oncotarget
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/27932991/cannabidiol-modulates-the-immunophenotype-and-inhibits-the-activation-of-the-inflammasome-in-human-gingival-mesenchymal-stem-cells
#8
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/27931512/xenotransplanted-pig-sertoli-cells-inhibit-both-the-alternative-and-classical-pathways-of-complement-mediated-cell-lysis-while-pig-islets-are-killed
#9
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SCs) survive xenotransplantation long term (90 days) without immunosuppression, making SCs an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies and the activation of the complement cascade. Using an in vitro cytotoxicity assay, wherein cells were cultured with human serum and complement, we demonstrated that neonatal pig SCs (NPSCs) are resistant to complement-mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46), and decay-accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPIs), which served as non-immune-privileged controls...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27929130/identification-of-a-cd133-cd55-population-functions-as-a-fetal-common-skeletal-progenitor
#10
Lihong Weng, Xingbin Hu, Bijender Kumar, Mayra Garcia, Ivan Todorov, Xiaoman Jung, Guido Marcucci, Stephen J Forman, Ching-Cheng Chen
In this study, we identified a CD105+CD90.1-CD133-CD55- (CD133-CD55-) population in the fetal skeletal element that can generate bone and bone marrow. Besides osteoblasts and chondrocytes, the CD133-CD55- common progenitors can give rise to marrow reticular stromal cells and perivascular mesenchymal progenitors suggesting they function as the fetal common skeletal progenitor. Suppression of CXCL12 and Kitl expression in CD133-CD55- common progenitors severely disrupted the BM niche formation but not bone generation...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27812245/paroxysmal-nocturnal-hemoglobinuria-from-bench-to-bed
#11
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/27736290/antibodies-against-complement-regulatory-proteins-on-platelets-in-immune-thrombocytopenia
#12
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/27694521/mutations-in-the-phosphatidylinositol-glycan-c-pigc-gene-are-associated-with-epilepsy-and-intellectual-disability
#13
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
#14
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/27667587/expression-pattern-of-cd55-and-cd59-on-red-blood-cells-in-sickle-cell-disease
#15
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...
March 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27604318/exploration-and-detection-of-potential-regulatory-variants-in-refractive-error-gwas
#16
Xuan Liao, ChangJun Lan, Dan Liao, Jing Tian, XiuQi Huang
Refractive error (RE) is a complex multifactorial disease. Genome-wide association studies (GWAS) have provided significant insight into the genetic architecture and identified plenty of robust genetic variations or single nucleotide polymorphisms (SNPs) associated with complex disease. A major current challenge is to convert those resources into causal variants and target genes. We used RegulomeDB and HaploReg to annotate regulatory information onto associated SNPs derived from the two largest RE GWAS, and additional SNPs in linkage disequilibrium (LD) with GWAS significant SNPs...
2016: Scientific Reports
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
#17
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/27566455/pulmonary-sarcoidosis-is-associated-with-exosomal-vitamin-d-binding-protein-and-inflammatory-molecules
#18
Maria-Jose Martinez-Bravo, Casper J E Wahlund, Khaleda Rahman Qazi, Robert Moulder, Ana Lukic, Olof Rådmark, Riitta Lahesmaa, Johan Grunewald, Anders Eklund, Susanne Gabrielsson
BACKGROUND: Sarcoidosis is an inflammatory granulomatous disorder characterized by accumulation of TH1-type CD4(+) T cells and immune effector cells within affected organs, most frequently the lungs. Exosomes are extracellular vesicles conveying intercellular communication with possible diagnostic and therapeutic applications. OBJECTIVES: We aimed to provide an understanding of the proinflammatory role of bronchoalveolar lavage fluid (BALF) exosomes in patients with sarcoidosis and to find candidates for disease biomarkers...
August 23, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27521598/activation-of-cd35-and-cd55-in-hiv-associated-normal-and-pre-eclamptic-pregnant-women
#19
R Khan, K Maduray, J Moodley, T Naicker
OBJECTIVE: The delicate balance which exists between complement activation and its regulation is altered in HIV infection and pregnancy disorders such as pre-eclampsia. Therefore, the purpose of this study was to investigate the expression of complement regulatory (Creg) proteins (CD35 and CD55) in HIV associated normal and pre-eclamptic pregnancies. STUDY DESIGN: The total study population (n=100) consisted of normotensive pregnant (n=50) and pre-eclamptic (n=50) women...
September 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27517501/genetic-strategies-to-bring-islet-xenotransplantation-to-the-clinic
#20
Wayne J Hawthorne, Andrew M Lew, Helen E Thomas
PURPOSE OF REVIEW: Despite the benefits of islet and pancreas allotransplantation, their widespread use in type 1 diabetes is limited because of the paucity of suitable donors. Porcine xenotransplantation offers an alternative, and advances in genetic modification of pigs have opened up new potential for its clinical use. This review outlines the barriers to successful islet xenotransplantation, and genetic modifications that have been tested to overcome these. RECENT FINDINGS: Islets from pigs lacking α1,3-galactosyltransferase, to prevent hyperacute rejection, are now used as a background strain for further genetic modifications...
October 2016: Current Opinion in Organ Transplantation
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