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Petra D Cravens, Rehana Z Hussain, William A Miller-Little, Li-Hong Ben, Benjamin M Segal, Emily Herndon, Olaf Stüve
BACKGROUND: Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS...
2016: PloS One
Irene Vacca, Elena Del Tordello, Gianmarco Gasperini, Alfredo Pezzicoli, Martina Di Fede, Silvia Rossi Paccani, Sara Marchi, Tsisti D Mubaiwa, Lauren E Hartley-Tassell, Michael P Jennings, Kate L Seib, Vega Masignani, Mariagrazia Pizza, Davide Serruto, Beatrice Aricò, Isabel Delany
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through a conserved Arg-rich region that is the target of two proteases, the meningococcal NalP and human lactoferrin (hLf). In this work, in vitro studies showed that recombinant NHBA protein was able to bind epithelial cells and mutations of the Arg-rich tract abrogated this binding. All N-terminal and C-terminal fragments generated by NalP or hLf cleavage, regardless of the presence or absence of the Arg-rich region, did not bind to cells, indicating that a correct positioning of the Arg-rich region within the full length protein is crucial...
2016: PloS One
Teresa E Twaroch, Mirela Curin, Katja Sterflinger, Margit Focke-Tejkl, Ines Swoboda, Rudolf Valenta
BACKGROUND: The mould Alternaria alternata is an important source of respiratory allergens. A. alternata extracts show great variations regarding allergenic potency. The aim of this study was to generate antibody probes specific for important Alternaria allergens and to use them to study allergen expression, depending on different culture conditions, as well as to search for cross-reactive allergens in other mould species. METHODS: Synthetic peptides from antigenic regions of A...
October 26, 2016: International Archives of Allergy and Immunology
Liyan Kong, Jiaming Zhu, Wen Wang, Lehe Jin, Yanjiao Fu, Bohui Duan, Liang Tan
As an integral glycoprotein on the surface of endothelial cells, thrombomodulin (TM) has very high affinity for thrombin. TM has been regarded to be a marker of endothelial damage since it can be released during endothelial cell injury. In this work, a highly sensitive fluorescence method for the quantitative detection of TM was developed. TM antibody (Ab) and bovine serum albumin (BSA) were bound on gold nanoparticles (AuNPs) to construct BSA-AuNPs-Ab nanocomposites and they were characterized by transmission electron microscope and UV-vis spectrophotometry...
October 17, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Jay N Lozier, Mark T Kloos, Elizabeth P Merricks, Nathaly Lemoine, Margaret H Whitford, Robin A Raymer, Dwight A Bellinger, Timothy C Nichols
Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons...
2016: Comparative Medicine
Marina C Pils, Karla Dreckmann, Katharina Jansson, Silke Glage, Nadine Held, Wiebke Sommer, Florian Länger, Murat Avsar, Gregor Warnecke, André Bleich
Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 Göttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation model and received tacrolimus and steroids as well as irradiation or CD8 antibody for immunosuppression...
2016: Comparative Medicine
Adrian Guthals, Yutian Gan, Laura Murray, Yongmei Chen, Jeremy Stinson, Gerald R Nakamura, Jennie R Lill, Wendy Sandoval, Nuno Bandeira
One direct route for the discovery of therapeutic human monoclonal antibodies (mAbs) involves the isolation of peripheral B cells from survivors/sero-positive individuals after exposure to an infectious reagent or disease etiology followed by single-cell sequencing or hybridoma generation. Peripheral B cells, however, are not always easy to obtain and only represent a small percentage of the total B cell population across all bodily tissues. Although it has been demonstrated that tandem mass spectrometry (MS/MS) techniques can interrogate the expressed polyclonal antibody (pAb) response to an antigen in vivo, all current approaches identify MS/MS spectra against databases derived from genetic sequencing of B cells from the same patient...
October 25, 2016: Journal of Proteome Research
Dian Su, Carl K Ng, Mehraban Khosraviani, Shang-Fan Yu, Ely Cosino, Surinder Kaur, Keyang Xu
Affinity capture liquid chromatography-mass spectrometry (LC-MS) intact antibody assay has been widely used for direct drug-to-antibody ratio (DAR) and catabolite characterization of antibody-drug conjugates (ADCs). However, the intact mass spectra of new ADCs, which incorporate new types of linkers and/or payloads other than maytansines and auristatins, are more complex than those examined previously. The current method has showed some limitations in elucidating certain structural modifications. Herein, we report an alternative analytical approach for ADCs, such as THIOMABTM antibody-drug conjugates (TDCs), where the linker-drugs are site-specifically conjugated in the Fab region...
October 25, 2016: Analytical Chemistry
Trinh L Dinh, Kevin C Ngan, Charles B Shoemaker, David R Walt
This paper provides insights into the performance of single-molecule array (Simoa) immunoassay by examining the effects of various capture and detector antibody-antigen binding kinetic parameters. Simoa is similar to other immunoassays in that the overall Simoa performance is heavily dependent on the choice of antibodies; however, little is known about how the different properties of the antibodies result in the wide variations in assay performance. Here, we focus on antibody-antigen binding kinetics and demonstrate how the association (kon) and dissociation (koff) rate constants of the capture and detection antibodies affect Simoa performance...
October 25, 2016: Analytical Chemistry
L Hepburn, D J Hijnen, B R Sellman, T Mustelin, M A Sleeman, R D May, I Strickland
Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of UK children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonised with Staphylococcus aureus (S. aureus) and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitisation, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection...
October 25, 2016: British Journal of Dermatology
Hiroko Kitahara, Mariko Hirai, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition...
October 21, 2016: Oncology Reports
Liyan Wen, Sha Yang, Ping Zhu, Yingxin Yu, Xiaoyan Qiu, Ning Fu, Yanjun Liu
Cancer-associated antigen 215 (CA215) is an immunoglobulin molecule expressed by numerous tumor types. Membrane‑bound and soluble CA215 have been detected in the majority of cancer cells and rarely identified in normal tissues. In addition, CA215C is a carbohydrate‑associated epitope in the variable region of CA215, which is specifically recognized by the monoclonal antibody, RP215. However, CA215C is not a suitable vaccine candidate as it is a thymus‑independent antigen. In the present study, RP215 was used as a target to screen short peptide mimics of CA215C from a phage display peptide library...
October 19, 2016: Molecular Medicine Reports
Efrem S Lim, Daniel Brennan
No abstract text is available yet for this article.
October 24, 2016: Transplantation
Matthew C Choy, Kumar Visvanathan, Peter De Cruz
Inflammatory bowel diseases (IBDs) are thought to develop as a result of complex interactions between host genetics, the immune system and the environment including the gut microbiome. Although an improved knowledge of the immunopathogenesis of IBDs has led to great advances in therapy such as the highly effective anti-tumor necrosis factor class of medications, a significant proportion of patients with Crohn's disease and ulcerative colitis do not respond to anti-tumor necrosis factor antibodies. Further understanding of the different immune pathways involved in the genesis of chronic intestinal inflammation is required to help find effective treatments for IBDs...
October 21, 2016: Inflammatory Bowel Diseases
E Lepiarczyk, A Dudek, J Kaleczyc, M Majewski, W Markiewicz, P Radziszewski, A Bossowska
Resiniferatoxin (RTX) is used as experimental drug therapy for a range of neurogenic urinary bladder disorders. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine urinary bladder after intravesical RTX instillation. The CaMG neurons were visualized with retrograde tracer Fast Blue (FB) and their chemical profile was disclosed with double-labelling immunohistochemistry using antibodies against tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), calbindin (CB), galanin (GAL) and neuronal nitric oxide synthase (nNOS)...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
A Rybicka, C Eyileten, B Taciak, J Mucha, K Majchrzak, E Hellmen, M Krol
Cancer stem-like cells as cells with ability to self-renewal and potential to differentiate into various types of cells are known to be responsible for tumour initiation, recurrence and drug resistance. Hence a comprehensive research is concentrated on discovering cancer stem-like cells biology and interdependence between them and other cells. The aim of our study was to evaluate the impact of macrophages on cancer stem-like cells in canine mammary carcinomas. As recent studies indicated presence of macrophages in cancer environment stimulates cancer cells into more motile and invasive cells by acquisition of macrophage phenotypes...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Sujin Ahn, Peng Zhang, Hyunung Yu, Seungah Lee, Seong Ho Kang
Super-localization of immunoplasmonic nanotags on antibody-bound gold-nanoislands (GNIs) along the x, y coordinates was determined using total internal reflection scattering-based super-resolution microscopy (TIRS-SRM) at subdiffraction limit resolu-tion. Individual immunoplasmonic nanotags (20-nm silver nanoparticles) and 100-nm GNIs were selectively acquired in the eva-nescent field layer by wavelength-dependent plasmonic scattering using two illumination lasers (405 nm and 635 nm, respectively). Alpha-fetoprotein (AFP), a liver cancer-related model protein, was immobilized as a target molecule on the GNI arrays...
October 25, 2016: Analytical Chemistry
Bryan H Norman, Jeff S McDermott
The neurotrophin nerve growth factor (NGF) has been implicated as a key mediator of chronic pain. NGF binds the tropomysin receptor kinase A (TrkA) and p75, resulting in the activation of downstream signaling pathways that have been linked to pro-nociception. While anti-NGF antibodies have demonstrated analgesia both preclinically and in patients, the mechanism of action of these agents remains unclear. We describe ligands targeting NGF, its receptors, and downstream/related targets. This Perspective highlights large and small molecule approaches to targeting the NGF-TrkA pathway both extra- and intracellularly...
October 25, 2016: Journal of Medicinal Chemistry
Zdenka Cicova, Mario Dejung, Tomas Skalicky, Nicole Eisenhuth, Steffen Hanselmann, Brooke Morriswood, Luisa M Figueiredo, Falk Butter, Christian J Janzen
Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study...
October 25, 2016: Scientific Reports
Der-Shan Sun, Pei-Hsun Ho, Hsin-Hou Chang
Venomous snakebites are lethal and occur frequently worldwide each year, and receiving the antivenom antibody is currently the most effective treatment. However, the specific antivenom might be unavailable in remote areas. Snakebites by Viperidae usually lead to hemorrhage and mortality if untreated. In the present study, challenges of rattlesnake (Crotalus atrox) venom markedly increased the circulating soluble P-selectin (sP-sel) level, but not P-selectin (P-sel, Selp(-/-)) mutants, in wild-type mice. Because sP-sel enhances coagulation through the P-selectin ligand 1 (PSGL-1, Selplg) pathway to produce tissue factor-positive microparticles, we hypothesized that increasing the plasma sP-sel level can be a self-rescue response in hosts against snake venom-mediated suppression of the coagulation system...
October 25, 2016: Scientific Reports
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