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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
#1
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
#2
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...
January 2, 2017: Virology
https://www.readbyqxmd.com/read/28054735/initial-study-of-%C3%AE-1-3-galactosyltransferase-gene-knockout-cd46-pig-full-thickness-corneal-xenografts-in-rhesus-monkeys
#3
Xiaojuan Dong, Hidetaka Hara, Ying Wang, Li Wang, Yingnan Zhang, David K C Cooper, Yifan Dai, Zhiqiang Pan
BACKGROUND: To investigate graft survival after full-thickness corneal xenotransplantation from α1,3-galactosyltransferase gene-knockout (GTKO) pigs expressing a human complement regulatory protein (GTKO/CD46 pigs) in rhesus monkeys. METHODS: Rhesus monkeys (n=10) were transplanted with full-thickness corneas from wild-type (WT; n=4) and GTKO/CD46 (n=4) pigs or from monkeys (n=2). All recipient monkeys received post-transplant subconjunctival injections of betamethasone...
January 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28042780/modulation-of-the-type-i-interferon-response-defines-the-sensitivity-of-human-melanoma-cells-to-oncolytic-measles-virus
#4
Ferdaous Allagui, Carole Achard, Clarisse Panterne, Chantal Combredet, Nathalie Labarrière, Brigitte Dréno, Amel Benammar Elgaaied, Daniel Pouliquen, Frédéric Tangy, Jean-François Fonteneau, Marcela Grégoire, Nicolas Boisgerault
BACKGROUND: Oncolytic viruses such as live-attenuated, vaccine strains of measles virus (MV) have recently emerged as promising cancer treatments, having shown significant antitumor activity against a large variety of human tumors. OBJECTIVE: Our study aims at determining which parameters define the sensitivity of human melanoma cells to oncolytic MV infection. METHOD: We analyzed both in vitro and in vivo the oncolytic activity of MV against a panel of human melanoma cell lines established in our laboratory...
January 2, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/27974740/a-case-report-and-literature-review-of-eculizumab-withdrawal-in-atypical-hemolytic-uremic-syndrome
#5
Borja Quiroga, Alberto de Lorenzo, Cristina Vega, Fernando de Alvaro
BACKGROUND Recent advances in the treatment of atypical hemolytic-uremic syndrome (aHUS) have resulted to better long-term survival rates for patients with this life-threatening disease. However, many questions remain such as whether or not long-term treatment is necessary in some patients and what are the risks of prolonged therapy. CASE REPORT Here, we discuss the case of a 37-year-old woman with CFH and CD46 genetic abnormalities who developed aHUS with severe renal failure. She was successfully treated with three doses of rituximab and a three month treatment with eculizumab...
December 15, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27932991/cannabidiol-modulates-the-immunophenotype-and-inhibits-the-activation-of-the-inflammasome-in-human-gingival-mesenchymal-stem-cells
#6
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/27932211/a-novel-class-of-somatic-mutations-in-blood-detected-preferentially-in-cd8-cells
#7
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
December 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
#8
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/27921411/association-of-cd46-ivs1-1724-c-g-single-nucleotide-polymorphism-in-iranian-women-with-unexplained-recurrent-spontaneous-abortion-ursa
#9
Shiva Abdi-Shayan, Amir Monfaredan, Zahra Moradi, Mehrangiz Rajaii Oskoui, Tohid Kazemi
There are several known and unknown factors for unexplained recurrent spontaneous abortion (URSA). Among them, complement regulatory protein CD46 plays a pivotal role in preventing uncontrolled activation of complement and successful continuation of pregnancy. We aimed in this study to investigate the possible association of CD46 IVS1-1724 C>G polymorphism with RSA in Iranian women. 141 women with RSA and 153 women with normal pregnancy were enrolled in this study. RSA was confirmed as the history of having at least three consecutive abortions without any known immunologic, pathologic and genetic reason...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27901098/tumor-specific-delivery-of-biologics-by-a-novel-t-cell-line-hozot
#10
Teppei Onishi, Hiroshi Tazawa, Yuuri Hashimoto, Makoto Takeuchi, Takeshi Otani, Shuji Nakamura, Fuminori Sakurai, Hiroyuki Mizuguchi, Hiroyuki Kishimoto, Yuzo Umeda, Yasuhiro Shirakawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
"Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27865262/soluble-forms-of-cd46-are-detected-in-bos-taurus-plasma-and-neutralize-bvdv-the-bovine-pestivirus
#11
Nidal Alzamel, Calixte Bayrou, Annabelle Decreux, Daniel Desmecht
The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides, 66EQIV69 and 82GQVLAL87, located on antiparallel beta sheets in the most distal complement control protein module (CCP1), provide the attachment platform. In the present study, we reveal new CD46-encoding transcripts that are predicted to encode CCP1-containing soluble forms. Further, we show that the serum of most adult cattle contains soluble CD46 (sCD46) and that a recombinant soluble isoform neutralizes BVDV infectivity in an in vitro assay...
December 2016: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/27794168/cd46-accelerates-macrophage-mediated-host-susceptibility-to-meningococcal-sepsis-in-a-murine-model
#12
Xiao Wang, Ding Zhang, Mikael Sjölinder, Yi Wan, Hong Sjölinder
CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygous mice (CD46(+/+) ) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46(+/+) mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1β In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation...
October 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27782084/measles-to-the-rescue-a-review-of-oncolytic-measles-virus
#13
REVIEW
Sarah Aref, Katharine Bailey, Adele Fielding
Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis...
October 22, 2016: Viruses
https://www.readbyqxmd.com/read/27739531/non-random-pairing-of-cd46-isoforms-with-skewing-towards-bc2-and-c2-in-activated-and-memory-effector-t-cells
#14
Aida S Hansen, Bettina B Bundgaard, Bjarne K Møller, Per Höllsberg
CD46 is a glycoprotein with important functions in innate and adaptive immune responses. Functionally different isoforms are generated by alternative splicing at exons 7-9 (BC and C isoforms) and exon 13 (CYT-1 and CYT-2 isoforms) giving rise to BC1, BC2, C1 and C2. We developed a novel real-time PCR assay that allows quantitative comparisons between these isoforms. Their relative frequency in CD4(+) T cells from 100 donors revealed a distribution with high interpersonally variability. Importantly, the distribution between the isoforms was not random and although splicing favoured inclusion of exon 8 (BC isoforms), exclusion of exon 8 (C isoforms) was significantly linked to exclusion of exon 13 (CYT-2 isoforms)...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27718086/serological-and-genetic-complement-alterations-in-infection-induced-and-complement-mediated-hemolytic-uremic-syndrome
#15
Dineke Westra, Elena B Volokhina, Renate G van der Molen, Thea J A M van der Velden, Annelies Jeronimus-Klaasen, Joop Goertz, Valentina Gracchi, Eiske M Dorresteijn, Antonia H M Bouts, Mandy G Keijzer-Veen, Joanna A E van Wijk, Jaap A Bakker, Anja Roos, Lambert P van den Heuvel, Nicole C A J van de Kar
BACKGROUND: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. METHODS: Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS...
February 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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
#16
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/27666019/characterization-of-cd46-and-%C3%AE-1-integrin-dynamics-during-sperm-acrosome-reaction
#17
Michaela Frolikova, Natasa Sebkova, Lukas Ded, Katerina Dvorakova-Hortova
The acrosome reaction (AR) is a process of membrane fusion and lytic enzyme release, which enables sperm to penetrate the egg surroundings. It is widely recognized that specific sperm proteins form an active network prior to fertilization, and their dynamic relocation is crucial for the sperm-egg fusion. The unique presence of the membrane cofactor protein CD46 in the sperm acrosomal membrane was shown, however, its behaviour and connection with other sperm proteins has not been explored further. Using super resolution microscopy, we demonstrated a dynamic CD46 reorganisation over the sperm head during the AR, and its interaction with transmembrane protein integrins, which was confirmed by proximity ligation assay...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27645610/role-of-cd46-polymorphisms-in-the-occurrence-of-disease-in-young-chinese-men-with-human-adenovirus-type-55-infection
#18
Qi Lv, Hui Ding, Zi-Quan Liu, Hong-Wei Gao, Bao-Guo Yu, Zhou-Wei Wu, Hao-Jun Fan, Shi-Ke Hou
OBJECTIVE: Human adenovirus type 55 (HAdV-55) has recently caused multiple outbreaks. This study examined polymorphisms in CD46 to determine their involvement in HAdV-55 infection. METHODS: A total of 214 study subjects infected with HAdV-55 were included in our study. The study subjects were divided into those with silent infections (n=91), minor infections (n=85), and severe infections (n=38). Ten single nucleotide polymorphisms (SNPs) from CD46 were examined...
September 20, 2016: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/27604429/safety-study-intraventricular-injection-of-a-modified-oncolytic-measles-virus-into-measles-immune-hcd46-transgenic-ifn%C3%AE-rko-mice
#19
Sangeet Lal, Kah-Whye Peng, Michael B Steele, Nathan Jenks, Hong Ma, Gary Kohanbash, Joanna J Phillips, Corey Raffel
The modified Edmonston vaccine strain of measles virus (MV) has shown potent oncolytic efficacy against various tumor types and is being investigated in clinical trials. Our laboratory showed that MV effectively kills medulloblastoma tumor cells in both localized disease and when tumor cells are disseminated through cerebrospinal fluid (CSF). Although the safety of repeated intracerebral injection of modified MV in rhesus macaques has been established, the safety of administering MV into CSF has not been adequately investigated...
December 2016: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/27554082/in-vivo-transduction-of-primitive-mobilized-hematopoietic-stem-cells-after-intravenous-injection-of-integrating-adenovirus-vectors
#20
Maximilian Richter, Kamola Saydaminova, Roma Yumul, Rohini Krishnan, Jing Liu, Eniko-Eva Nagy, Manvendra Singh, Zsuzsanna Izsvák, Roberto Cattaneo, Wolfgang Uckert, Donna Palmer, Philip Ng, Kevin G Haworth, Hans-Peter Kiem, Anja Ehrhardt, Thalia Papayannopoulou, André Lieber
Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35(++)) vector system...
November 3, 2016: Blood
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