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https://www.readbyqxmd.com/read/29775720/diagnosing-human-blood-clotting-deficiency
#1
REVIEW
Chong Cheen Ong, Subash C B Gopinath, Leong Wei Xian Rebecca, Veeradasan Perumal, Thangavel Lakshmipriya, Mohamed Shuaib Mohamed Saheed
There are different clotting factors present in blood, carries the clotting cascade and excessive bleeding may cause a deficiency in the clotting. Diagnosis of deficiency in clotting reduces the potential fatality. For enabling a sensor to detect the clotting factors, suitable probes such as antibody and aptamer have been used to capture the clotting factors on the sensing surface. Two major clotting factors were widely studied in detail for the diagnosis of clotting deficiency, which includes factor IX and thrombin...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29769092/mineralization-of-alpha-1-antitrypsin-inclusion-bodies-in-mmalton-alpha-1-antitrypsin-deficiency
#2
Francesco Callea, Isabella Giovannoni, Paola Francalanci, Renata Boldrini, Gavino Faa, Daniela Medicina, Valerio Nobili, Valeer J Desmet, Kamal Ishak, Kuniaki Seyama, Emanuele Bellacchio
BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency (AATD) of Z, Mmalton, Siiyama type is associated with liver storage of the mutant proteins and liver disease. The Z variant can be diagnosed on isoelectric focusing (IEF) while Mmalton and Siiyama may be missed or misdiagnosed with this technique. Therefore, molecular analysis is mandatory for their characterization. In particular, that holds true for the Mmalton variant as on IEF profile it resembles the wild M2 subtype. METHODS: This is a retrospective analysis involving review of medical records and of liver biopsy specimens from a series of Mmalton, Z and Siiyama Alpha-1-antitrypsin deficiency patients...
May 16, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29765910/a-promising-ifn-deficient-system-to-manufacture-ifn-sensitive-influenza-vaccine-virus
#3
Can Chen, Wenhui Fan, Jing Li, Weinan Zheng, Shuang Zhang, Limin Yang, Di Liu, Wenjun Liu, Lei Sun
Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29765016/b-cell-activation-and-plasma-cell-differentiation-are-inhibited-by-de-novo-dna-methylation
#4
Benjamin G Barwick, Christopher D Scharer, Ryan J Martinez, Madeline J Price, Alexander N Wein, Robert R Haines, Alexander P R Bally, Jacob E Kohlmeier, Jeremy M Boss
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#5
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763589/%C3%AE-1-antitrypsin-polymerizes-in-alveolar-macrophages-of-smokers-with-and-without-%C3%AE-1-antitrypsin-deficiency
#6
Erica Bazzan, Mariaenrica Tinè, Davide Biondini, Riccardo Benetti, Simonetta Baraldo, Graziella Turato, Stefano Fagiuoli, Aurelio Sonzogni, Chiara Rigobello, Federico Rea, Fiorella Calabrese, Maria Pia Foschino-Barbaro, Elena Miranda, David A Lomas, Marina Saetta, Manuel G Cosio
BACKGROUND: The deficiency of α1 -antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. AIMS: To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation...
May 12, 2018: Chest
https://www.readbyqxmd.com/read/29760157/methyl-cpg-binding-protein-2-mediates-antifibrotic-effects-in-scleroderma-fibroblasts
#7
Ye He, Pei-Suen Tsou, Dinesh Khanna, Amr H Sawalha
OBJECTIVE: Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. METHODS: Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro...
May 14, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29757592/the-profile-of-toll-like-receptor-2-tlr2-tlr4-and-their-cytosolic-downstream-signaling-pathway-in-common-variable-immunodeficiency-cvid-patients
#8
Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Mahdi Mahmoudi, Mohammad Mehdi Amiri, Farimah Masoumi, Saied Bokaie, Parsova Tavasolian, Rouzbeh Sanaei, Mona Moshiri, Naeimeh Tavakolinia, Tina Alinia, Gholamreza Azizi, Abbas Mirshafiey
Common variable immunodeficiency (CVID) is the most common clinical primary antibody deficiency, characterized by increased susceptibility to recurrent bacterial infections. Since Toll-like receptors (TLRs) play an important role in the maturation and differentiation of B-cells, TLRs' defect can be involved in the pathogenesis of CVID. Therefore, we evaluated the expression of TLR2 and TLR4 and their signaling pathway; also their association with autoimmunity, B-cell subtypes and response to pneumovax-23 were assessed in CVID patients...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29756268/does-rotational-thromboelastometry-accurately-predict-coagulation-status-in-patients-with-lupus-anticoagulant
#9
L Hensch, V Kostousov, K Bruzdoski, M Losos, M Pereira, M de Guzman, S Hui, J Teruya
INTRODUCTION: Rotational thromboelastometry (ROTEM) is increasingly used as a tool for monitoring coagulation status. However, ROTEM is susceptible to misinterpretation due to particular coagulation abnormalities. Here, we report the effects of lupus anticoagulant (LA) on ROTEM. METHODS: A prospective observational analysis was performed on 16 children with prior studies indicating the presence of LA or antiphospholipid antibodies. ROTEM analysis was performed, and samples were further analyzed by adding phospholipids (PL) to repeat ROTEM analysis if clotting time (CT) abnormalities were discovered with comparison to ROTEM using an equal volume of isotonic saline...
May 13, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29755980/importance-of-validating-antibodies-and-small-compound-inhibitors-using-genetic-knockout-studies-t-cell-receptor-induced-cyld-phosphorylation-by-ikk%C3%AE%C2%B5-tbk1-as-a-case-study
#10
Marie Lork, Marja Kreike, Jens Staal, Rudi Beyaert
CYLD is a deubiquitinating enzyme that plays a crucial role in immunity and inflammation as a negative regulator of NF-κB transcription factor and JNK kinase signaling. Defects in either of these pathways contribute to the progression of numerous inflammatory and autoimmune disorders. Therefore, we set out to unravel molecular mechanisms that control CYLD activity in the context of T cell receptor (TCR) signaling. More specifically, we focused on CYLD phosphorylation at Ser418, which can be detected upon immunoblotting of cell extracts with phospho(Ser418)-CYLD specific antibodies...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29755958/gut-microbiota-contributes-to-resistance-against-pneumococcal-pneumonia-in-immunodeficient-rag-mice
#11
Krysta M Felix, Ivan A Jaimez, Thuy-Vi V Nguyen, Heqing Ma, Walid A Raslan, Christina N Klinger, Kristian P Doyle, Hsin-Jung J Wu
Streptococcus pneumoniae causes infection-related mortality worldwide. Immunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable, yet little is known regarding S. pneumoniae- related pathogenesis and protection in immunocompromised hosts. Recently, strong interest has emerged in the gut microbiota's impact on lung diseases, or the "gut-lung axis." However, the mechanisms of gut microbiota protection against gut-distal lung diseases like pneumonia remain unclear...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29755476/transitional-b-cells-and-tlr9-responses-are-defective-in-selective-iga-deficiency
#12
Andri L Lemarquis, Helga K Einarsdottir, Rakel N Kristjansdottir, Ingileif Jonsdottir, Bjorn R Ludviksson
Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755449/immunization-elicits-antigen-specific-antibody-sequestration-in-dorsal-root-ganglia-sensory-neurons
#13
Manojkumar Gunasekaran, Prodyot K Chatterjee, Andrew Shih, Gavin H Imperato, Meghan Addorisio, Gopal Kumar, Annette Lee, John F Graf, Dan Meyer, Michael Marino, Christopher Puleo, Jeffrey Ashe, Maureen A Cox, Tak W Mak, Chad Bouton, Barbara Sherry, Betty Diamond, Ulf Andersson, Thomas R Coleman, Christine N Metz, Kevin J Tracey, Sangeeta S Chavan
The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754249/trpa1-channels-expression-in-non-neuronal-murine-lung-tissues-and-dispensability-for-hyperoxia-induced-alveolar-epithelial-hyperplasia
#14
Martina Kannler, Robin Lüling, Ali Önder Yildirim, Thomas Gudermann, Dirk Steinritz, Alexander Dietrich
Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells...
May 12, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29754190/allergic-and-immunologic-perspectives-of-inflammatory-bowel-disease
#15
REVIEW
Kofi Clarke, Jayakrishna Chintanaboina
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn's disease (CD), ulcerative colitis (UC), and a less common phenotype-indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut...
May 12, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29753791/obstructive-lymphangitis-precedes-colitis-in-murine-norovirus-infected-stat1-deficient-mice
#16
Audrey Seamons, Piper M Treuting, Stacey Meeker, Charlie Hsu, Jisun Paik, Thea Brabb, Sabine S Escobar, Jonathan S Alexander, Aaron Ericsson, Jason G Smith, Lillian Maggio-Price
Murine norovirus (MNV) is an RNA virus that can prove lethal in mice with impaired innate immunity. We found that MNV-4 infection of Stat1-/- mice was not lethal, but produced a 100% penetrant, previously undescribed lymphatic phenotype characterized by chronic-active lymphangitis with hepatitis, splenitis, and chronic cecal and colonic inflammation. Lesion pathogenesis progressed from early ileal enteritis and regional dilated lymphatics to lymphangitis, granulomatous changes in the liver and spleen, and ultimately, typhlocolitis...
May 10, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29752428/angiopoietin-like-protein-3-angptl3-deficiency-and-familial-combined-hypolipidemia
#17
Tarugi Patrizia, Bertolini Stefano, Calandra Sebastiano
Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase...
April 12, 2018: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29748606/cd47-ligation-induced-cell-death-in-t-acute-lymphoblastic-leukemia
#18
Pascal Leclair, Chi-Chao Liu, Mahdis Monajemi, Gregor S Reid, Laura M Sly, Chinten James Lim
CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748549/genotype-i-of-japanese-encephalitis-virus-virus-like-particles-elicit-sterilizing-immunity-against-genotype-i-and-iii-viral-challenge-in-swine
#19
Yi-Chin Fan, Jo-Mei Chen, Jen-Wei Lin, Yi-Ying Chen, Guan-Hong Wu, Kuan-Hsuan Su, Ming-Tang Chiou, Shang-Rung Wu, Ji-Hang Yin, Jiunn-Wang Liao, Gwong-Jen J Chang, Shyan-Song Chiou
Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29746581/human-neuroglial-cells-internalize-borrelia-burgdorferi-by-coiling-phagocytosis-mediated-by-daam1
#20
Shanna K Williams, Zachary P Weiner, Robert D Gilmore
Borrelia burgdorferi, the agent of Lyme borreliosis, can elude hosts' innate and adaptive immunity as part of the course of infection. The ability of B. burgdorferi to invade or be internalized by host cells in vitro has been proposed as a mechanism for the pathogen to evade immune responses or antimicrobials. We have previously shown that B. burgdorferi can be internalized by human neuroglial cells. In this study we demonstrate that these cells take up B. burgdorferi via coiling phagocytosis mediated by the formin, Daam1, a process similarly described for human macrophages...
2018: PloS One
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