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https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#1
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914090/measuring-antibody-orientation-at-the-bacterial-surface
#2
Oonagh Shannon, Pontus Nordenfelt
Many bacteria have the ability to interact with antibodies as a means to circumvent the immune response. This includes binding to the Fc portion of antibodies, effectively reversing the antibody orientation and thus decreasing the Fc-mediated immune signaling. Since antibody orientation at the bacterial surface has been shown to be important in human disease, it is valuable to be able to assess how antibodies are interacting with bacterial pathogens. Here, we describe a method to measure the proportion of human IgG that are bound via their Fc or Fabs to a bacterial surface...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914089/generating-and-purifying-fab-fragments-from-human-and-mouse-igg-using-the-bacterial-enzymes-ides-speb-and-kgp
#3
Jonathan Sjögren, Linda Andersson, Malin Mejàre, Fredrik Olsson
Fab fragments are valuable research tools in various areas of science including applications in imaging, binding studies, removal of Fc-mediated effector functions, mass spectrometry, infection biology, and many others. The enzymatic tools for the generation of Fab fragments have been discovered through basic research within the field of molecular bacterial pathogenesis. Today, these enzymes are widely applied as research tools and in this chapter, we describe methodologies based on bacterial enzymes to generate Fab fragments from both human and mouse IgG...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913990/sirukumab-a-potential-treatment-for-mood-disorders
#4
REVIEW
Aileen J Zhou, Yena Lee, Giacomo Salvadore, Benjamin Hsu, Trehani M Fonseka, Sidney H Kennedy, Roger S McIntyre
Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation...
December 2, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#5
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27913434/a-study-of-tp53-rna-splicing-illustrates-pitfalls-of-rna-seq-methodology
#6
Sunali Mehta, Peter Tsai, Annette Lasham, Hamish Campbell, Roger Reddel, Antony Braithwaite, Cristin Print
TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913140/comparative-analysis-of-tcdd-induced-ahr-mediated-gene-expression-in-human-mouse-and-rat-primary-b-cells
#7
Natalia Kovalova, Rance Nault, Robert Crawford, Timothy R Zacharewski, Norbert E Kaminski
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation...
November 29, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27912986/a-phase-iii-observer-blind-randomized-controlled-study-to-evaluate-the-immune-response-and-the-correlation-with-nasopharyngeal-carriage-after-immunization-of-university-students-with-a-quadrivalent-meningococcal-acwy-glycoconjugate-or-serogroup-b-meningococcal
#8
Robert C Read, Peter Dull, Xilian Bai, Kate Nolan, Jamie Findlow, Rohit Bazaz, Annett Kleinschmidt, Maggie McCarthy, Huajun Wang, Daniela Toneatto, Ray Borrow
BACKGROUND: University students have high rates of pharyngeal carriage of Neisseria meningitidis. Interruption of carriage acquisition is an important mechanism of vaccines for inducing herd protection. 4CMenB and MenACWY-CRM vaccines have been shown to be immunogenic against meningococcal serogroups B and ACWY respectively in younger age groups, and also to elicit a modest impact on meningococcal carriage in vaccinated students. However, vaccine responses in university students and the impact of serum bactericidal antibody (SBA) titers on meningococcal carriage are undetermined...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#9
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27912789/dynamics-of-antigenemia-and-transmission-intensity-of-wuchereria-bancrofti-following-cessation-of-mass-drug-administration-in-a-formerly-highly-endemic-region-of-mali
#10
Yaya I Coulibaly, Siaka Y Coulibaly, Housseini Dolo, Siaka Konate, Abdallah A Diallo, Salif S Doumbia, Lamine Soumaoro, Michel E Coulibaly, Ilo Dicko, Moussa B Sangare, Benoit Dembele, Modibo Sangare, Massitan Dembele, Yeya T Touré, Louise Kelly-Hope, Katja Polman, Dominique Kyelem, Sekou F Traore, Moses Bockarie, Amy D Klion, Thomas B Nutman
BACKGROUND: After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. METHODS: Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6-7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012...
December 3, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27911694/seroprevalence-of-babesia-microti-in-individuals-with-lyme-disease
#11
Sabino R Curcio, Laurel P Tria, Azad L Gucwa
INTRODUCTION: Babesiosis is an emerging tick-borne disease (TBD) caused by Babesia microti, an intracellular parasite of red blood cells. Currently, it is the highest ranked pathogen transmitted by blood transfusion. Most healthy individuals infected with B. microti are asymptomatic, but may be at risk for chronic infection. Similar to Lyme disease transmitted by Borrelia burgdorferi, B. microti is spread by Ixodes scapularis ticks. The rate of coinfection with these TBDs in humans is unclear as most studies have focused their prevalence in ticks or rodent reservoirs...
December 2016: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/27911254/neutralizing-and-enhancing-antibody-responses-to-five-genotypes-of-dengue-virus-type-1-denv-1-in-denv-1-patients
#12
Atsushi Yamanaka, Meng Ling Moi, Tomohiko Takasaki, Ichiro Kurane, Eiji Konishi
Dengue virus has four distinct serotypes, DENV-1-4, with 4-6 genotypes in each serotype. The World Health Organization recommends tetravalent formulations including one genotype of each serotype as safe and effective dengue vaccines. Here, we investigated the impact of genotype on the neutralizing antibody responses to DENV-1 in humans. Convalescent sera collected from patients with primary infection of DENV-1 were examined for neutralizing antibody against single-round infectious particles of the five DENV-1 genotypes (GI-GV)...
December 2, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27911216/validation-of-antibody-reagents-for-mucin-analysis-in-chronic-inflammatory-airway-diseases
#13
Thorsten Krause, Niels Röckendorf, Karoline I Gaede, Katrin Ramaker, Heike Sinnecker, Andreas Frey
In chronic inflammatory airway diseases, mucins display disease-related alterations in quantity, composition and glycosylation. This opens the possibility to diagnose and monitor inflammatory airway disorders and their exacerbation based on mucin properties. For such an approach to be reasonably versatile and diagnostically meaningful, the mucin of interest must be captured in a reliable, patient-independent way. To identify appropriate mucin-specific reagents, we tested anti-mucin antibodies on mucin-content-standardized, human bronchoalveolar lavage fluid samples in immunoblot assays...
December 2, 2016: MAbs
https://www.readbyqxmd.com/read/27911041/impact-of-rabies-vaccination-history-on-attainment-of-an-adequate-antibody-titre-among-dogs-tested-for-international-travel-certification-israel-2010-2014
#14
B Yakobson, N Taylor, N Dveres, S Rotblat, Ż Spero, E W Lankau, J Maki
Rabies is endemic in wildlife or domestic carnivore populations globally. Infection of domestic dogs is of particular concern in many areas. In regions where domestic animals are at risk of exposure to rabies virus, dogs should be routinely vaccinated against rabies to protect both pet and human populations. Many countries require demonstration of an adequate level of serum rabies neutralizing antibodies to permit entry of dogs during international travel. We analysed rabies titres of dogs seeking travel certification in Israel to assess demographic and vaccine history factors associated with antibody titres below the acceptable threshold for travel certification...
December 2, 2016: Zoonoses and Public Health
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#15
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910950/human-antibody-3e1-targets-the-ha-stem-region-of-h1n1-and-h5n6-influenza-a-viruses
#16
Wenshuai Wang, Xiaoyu Sun, Yanbing Li, Jinpeng Su, Zhiyang Ling, Tianlong Zhang, Fang Wang, Hong Zhang, Hualan Chen, Jianping Ding, Bing Sun
As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27909576/zika-antiviral-chemotherapy-identification-of-drugs-and-promising-starting-points-for-drug-discovery-from-an-fda-approved-library
#17
Bruno S Pascoalino, Gilles Courtemanche, Marli T Cordeiro, Laura H V G Gil, Lucio Freitas-Junior
Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account...
2016: F1000Research
https://www.readbyqxmd.com/read/27909397/novel-non-phosphorylated-serine-9-21-gsk3%C3%AE-%C3%AE-antibodies-expanding-the-tools-for-studying-gsk3-regulation
#18
Tessa Grabinski, Nicholas M Kanaan
Glycogen synthase kinase 3 (GSK3) β and α are serine/threonine kinases involved in many biological processes. A primary mechanism of GSK3 activity regulation is phosphorylation of N-terminal serine (S) residues (S9 in GSK3β, S21 in GSK3α). Phosphorylation is inhibitory to GSK3 kinase activity because the phosphorylated N-terminus acts as a competitive inhibitor for primed substrates. Despite widespread interest in GSK3 across most fields of biology, the research community does not have reagents that specifically react with nonphosphoS9/21 GSK3β/α (the so-called "active" form)...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27909097/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#19
Bianca N Mason, Eric A Kaiser, Adisa Kuburas, Maria-Cristina M Loomis, John A Latham, Leon F Garcia-Martinez, Andrew F Russo
: The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. While migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the central nervous system, we used CGRP-induced light aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal, IP) injection of CGRP resulted in light aversive behavior in wild-type CD1 mice similar to aversion previously seen following central (intracerebroventricular, ICV) injection...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909085/a-negative-antinuclear-antibody-does-not-indicate-autoantibody-negativity-in-myositis-role-of-anticytoplasmic-antibody-as-a-screening-test-for-antisynthetase-syndrome
#20
Rohit Aggarwal, Namrata Dhillon, Noreen Fertig, Diane Koontz, Zengbiao Qi, Chester V Oddis
OBJECTIVE: To evaluate the utility of anticytoplasmic autoantibody (anti-CytAb) in antisynthetase antibody-positive (anti-SynAb+) patients. METHODS: Anti-SynAb+ patients were evaluated for antinuclear antibody (ANA) and anti-CytAb [cytoplasmic staining on indirect immunofluorescence (IIF)] positivity. Anti-SynAb+ patients included those possessing anti-Jo1 and other antisynthetase autoantibodies. Control groups included scleroderma, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and healthy subjects...
December 1, 2016: Journal of Rheumatology
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