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https://www.readbyqxmd.com/read/28797937/immunohistochemical-characterization-and-sensitivity-to-human-adenovirus-serotypes-3-5-and-11p-of-new-cell-lines-derived-from-human-diffuse-grade-ii-to-iv-gliomas
#1
Minna Niittykoski, Mikael von Und Zu Fraunberg, Miika Martikainen, Tuomas Rauramaa, Arto Immonen, Susanna Koponen, Ville Leinonen, Markus Vähä-Koskela, Qiwei Zhang, Florian Kühnel, Ya-Fang Mei, Seppo Ylä-Herttuala, Juha E Jääskeläinen, Ari Hinkkanen
BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p...
August 3, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28789701/a-novel-bladder-cancer-specific-oncolytic-adenovirus-by-cd46-and-its-effect-combined-with-cisplatin-against-cancer-cells-of-car-negative-expression
#2
Wenjuan Cao, Junqiang Tian, Chong Li, Yanjun Gao, Xingchen Liu, Jianzhong Lu, Yuhan Wang, Zhiping Wang, Robert S Svatek, Ronald Rodriguez
BACKGROUND: Conditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can't be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. METHODS: We utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule...
August 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28752844/routine-use-of-clinical-exome-based-next-generation-sequencing-for-evaluation-of-patients-with-thrombotic-microangiopathies
#3
Joseph P Gaut, Sanjay Jain, John D Pfeifer, Katinka A Vigh-Conrad, Meagan Corliss, Mukesh K Sharma, Jonathan W Heusel, Catherine E Cottrell
Next-generation sequencing is increasingly used for clinical evaluation of patients presenting with thrombotic microangiopathies because it allows for simultaneous interrogation of multiple complement and coagulation pathway genes known to be associated with disease. However, the diagnostic yield is undefined in routine clinical practice. Historic studies relied on case-control cohorts, did not apply current guidelines for variant pathogenicity assessment, and used targeted gene enrichment combined with next-generation sequencing...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28715486/anti-neu5gc-and-anti-non-neu5gc-antibodies-in-healthy-humans
#4
Bingsi Gao, Cassandra Long, Whayoung Lee, Zhongqiang Zhang, Xiaotian Gao, Doug Landsittel, Mohamed Ezzelarab, David Ayares, Yuliang Huang, David K C Cooper, Yi Wang, Hidetaka Hara
Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28666265/cap-dependent-translational-control-of-oncolytic-measles-virus-infection-in-malignant-mesothelioma
#5
Blake A Jacobson, Ahad A Sadiq, Shaogeng Tang, Joe Jay-Dixon, Manish R Patel, Jeremy Drees, Brent S Sorenson, Stephen J Russell, Robert A Kratzke
Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28626544/atypical-hemolytic-uremic-syndrome-a-brief-review
#6
REVIEW
Kuixing Zhang, Yuxin Lu, Kevin T Harley, Minh-Ha Tran
Atypical hemolytic uremic syndrome (aHUS) is a disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The histopathologic lesions of aHUS include thrombotic microangiopathy involving the glomerular capillaries and thrombosis involving arterioles or interlobar arteries. Extra-renal manifestations occur in up to 20% of patients. The majority of aHUS is caused by complement system defects impairing ordinary regulatory mechanisms. Activating events therefore lead to unbridled, ongoing complement activity producing widespread endothelial injury...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28542228/alteration-of-membrane-complement-regulators-is-associated-with-transporter-status-in-patients-on-peritoneal-dialysis
#7
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/28476687/alternative-polyadenylation-expands-the-mrna-isoform-repertoire-of-human-cd46
#8
Phuong Thao Ly, Sze Jing Tang, Xavier Roca
Alternative polyadenylation is a prevalent mechanism regulating mammalian gene expression. While tandem 3'-Untranslated-Region (3'UTR) polyadenylation changes expression levels, Intronic PolyAdenylation generates shorter transcripts encoding truncated proteins. Intronic PolyAdenylation regulates 20% of genes and is especially common in receptor tyrosine-kinase transcripts, generating soluble repressors. Here we report that human CD46, encoding a TransMembrane repressor of complement and T-cell co-stimulator, expresses multiple isoforms by alternative polyadenylation...
August 20, 2017: Gene
https://www.readbyqxmd.com/read/28474373/angiopoietin-1-and-angiopoietin-2-protect-porcine-iliac-endothelial-cells-from-human-antibody-mediated-complement-dependent-cytotoxicity-through-phosphatidylinositide-3-kinase-akt-pathway-activation
#9
Hanchao Gao, Pengfei Chen, Ling Wei, Jia Xu, Lu Liu, Yanli Zhao, Hidetaka Hara, Dengke Pan, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
Cytokines play crucial roles in inflammation, but their role in xenotransplantation remains elusive. We assessed the role of several cytokines using an in vitro model of human antibody-mediated complement-dependent cytotoxicity (CDC). Recombinant human angiopoietin-1 (Ang-1) protected porcine iliac endothelial cells (PIECs) from human antibody-mediated CDC. Interestingly, human angiopoietin-2 (Ang-2) had a similar protective effect on PIECs. By flow cytometry analysis, the extent of human IgM and IgG binding to PIECs did not decrease when PIECs were exposed to Ang-1/Ang-2...
July 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28446314/-changes-of-neutrophil-cd64-in-patients-with-hematological-mali-gnancies-combined-with-bacterial-infections
#10
Xin Dai, Jian-Ping Li, Wen-Qian Li, Jian-Ming Feng
OBJECTIVE: To explore the changes of CD64 on surface of neutrophils in patients with hematological malignancies combined with bacterial infections. METHODS: Ninety-seven patients with hematological tumor admitted in our hospital from August 2014 to February 2016 were selected and divided into 2 groups: infection group(50 cases) and noninfection group(47 cases) according to their symptoms, physical sings and blood culture results for microbiologic detection. The CD46 index on surface of neutrophils, serum C- reactive protein (CRP), neutrophil count (NC) and procalcitonin (PCT) level were detected by flow cytometry...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28444759/dysregulated-cd46-shedding-interferes-with-th1-contraction-in-systemic-lupus-erythematosus
#11
Ursula Ellinghaus, Andrea Cortini, Christopher L Pinder, Gaelle Le Friec, Claudia Kemper, Timothy J Vyse
IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase...
July 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28413120/endosome-to-trans-golgi-network-transport-of-proprotein-convertase-7-is-mediated-by-a-cluster-of-basic-amino-acids-and-palmitoylated-cysteines
#12
Jeroen Declercq, Bruno Ramos-Molina, Ragna Sannerud, Bas Brouwers, Vincent P E G Pruniau, Sandra Meulemans, Evelyn Plets, Wim Annaert, John W M Creemers
Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network (TGN) but it shuttles between the plasma membrane and the TGN depending on sequences in the cytoplasmic tail. A short region containing a three amino acids motif, P(724)-L(725)-C(726), is essential and sufficient for internalization of PC7 but not for TGN localization, which requires the additional presence of the juxtamembrane region. In this study we have investigated the contribution of a cluster of basic amino acids and two reversibly palmitoylated cysteine residues to endocytic trafficking...
April 7, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#13
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 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28289848/genome-wide-associations-of-cd46-and-ifi44l-genetic-variants-with-neutralizing-antibody-response-to-measles-vaccine
#14
Iana H Haralambieva, Inna G Ovsyannikova, Richard B Kennedy, Beth R Larrabee, Michael T Zimmermann, Diane E Grill, Daniel J Schaid, Gregory A Poland
Population-based studies have revealed 2-10% measles vaccine failure rate even after two vaccine doses. While the mechanisms behind this remain unknown, we hypothesized that host genetic factors are likely to be involved. We performed a genome-wide association study of measles specific neutralizing antibody and IFNγ ELISPOT response in a combined sample of 2872 subjects. We identified two distinct chromosome 1 regions (previously associated with MMR-related febrile seizures), associated with vaccine-induced measles neutralizing antibody titers...
April 2017: Human Genetics
https://www.readbyqxmd.com/read/28273946/dysregulation-of-mcd46-and-scd46-contribute-to-the-pathogenesis-of-bullous-pemphigoid
#15
Pei Qiao, Erle Dang, Tianyu Cao, Hui Fang, Jieyu Zhang, Hongjiang Qiao, Gang Wang
Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199366/micrornas-regulating-cluster-of-differentiation-46-cd46-in-cardioembolic-and-non-cardioembolic-stroke
#16
Jun Rong Tan, Kay Sin Tan, Fung Lin Yong, Arunmozhiarasi Armugam, Chee Woon Wang, Kandiah Jeyaseelan, Peter Tsun-Hon Wong
Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5...
2017: PloS One
https://www.readbyqxmd.com/read/28187980/patients-with-hypertension-associated-thrombotic%C3%A2-microangiopathy-may-present-with%C3%A2-complement-abnormalities
#17
Sjoerd A M E G Timmermans, Myrurgia A Abdul-Hamid, Joris Vanderlocht, Jan G M C Damoiseaux, Chris P Reutelingsperger, Pieter van Paassen
Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28176476/recurrent-atypical-haemolytic-uraemic-syndrome-post-kidney-transplant-due-to-a-cd46-mutation-in-the-setting-of-smarcal1-mediated-inherited-kidney-disease
#18
REVIEW
Samuel Chan, Andrew J Mallett, Chirag Patel, Ross S Francis, David W Johnson, David W Mudge, Nicole M Isbel
Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28076980/status-of-sperm-born-oocyte-activating-factors-pawp-plc%C3%AE-and-sperm-chromatin-in-uncapacitated-capacitated-and-acrosome-reacted-conditions
#19
Marziyeh Tavalaee, Kazem Parivar, Abdol-Hossein Shahverdi, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
The aim of this study was to investigate the value of sperm factors PAWP and PLCζ involved in oocyte activation and sperm chromatin status, as indicators of sperm quality during uncapacitated, capacitated and acrosome-reacted conditions. Semen samples collected from 10 normozoospermic men and sperm factors PAWP, PLCζ, protamine deficiency and DNA fragmentation evaluated in fresh samples, processed sample by DGC (density gradient centrifugation), capacitated and acrosome reacted sperm, using immunofluorescence and flow cytometry...
January 12, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28056415/divergent-tropism-of-hhv-6ags-and-hhv-6bpl1-in-t-cells-expressing-different-cd46-isoform-patterns
#20
COMPARATIVE STUDY
Aida S Hansen, Bettina B Bundgaard, Mette Biltoft, Litten S Rossen, Per Höllsberg
CD46 is a receptor for HHV-6A, but its role as a receptor for HHV-6B is controversial. The significance of CD46 isoforms for HHV-6A and HHV-6B tropism is unknown. HHV-6AGS was able to initiate transcription of the viral genes U7 and U23 in the CD46(+)CD134(-) T-cell lines Peer, Jurkat, Molt3, and SupT1, whereas HHV-6BPL1 was only able to do so in Molt3 and SupT1, which expressed a CD46 isoform pattern different from Peer and Jurkat. The HHV-6BPL1-susceptible T-cell lines were characterized by low expression of the CD46 isoform BC2 and domination of isoforms containing the cytoplasmic tail, CYT-1...
February 2017: Virology
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