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Candy S Hwang, Lauren C Smith, Yoshihiro Natori, Beverly Ellis, Bin Zhou, Kim D Janda
The sharp increase in overdose deaths involving illicit opioid use has been declared a national crisis in the United States. This growing number of overdose deaths can in part be attributed to the increased frequency of fentanyl contamination in the US heroin supply. To combat this growing trend, we designed a vaccine containing a mixture of heroin and fentanyl hapten-conjugates as a proof-of-concept immunotherapy targeting a combination of these drugs. Rodents immunized with the admixture vaccine showed drug retention in serum and reduced distribution in the brain after administration of an intravenous bolus of heroin co-administered with fentanyl (10% w/w)...
March 20, 2018: ACS Chemical Neuroscience
De-Xin Kong, Fang Lv, Ben Hu, Li-Min Cao
Detection of triphenylmethane dyes (TDs), especially the widely used malachite green (MG) and crystal violet (CV), plays an important role in safety control of aquatic products. There are two chromatic forms of TDs: oxidized or reduced. Usually, only one form can be detected by reported ELISA antibodies. In this article, molecular shape superimposing and quantum mechanics calculation were employed to elucidate the differences between MG, CV, and their reduced chromatic forms (leucomalachite green, LMG and leucocrystal violet, LCV)...
March 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Inna A Galvidis, Zhanhui Wang, Rinat I Nuriev, Maksim A Burkin
The recognition spectrum of immunoassays developed on the basis of class-specific antibodies can include the several nearest analytes but rarely all of the desired representatives of the group. The situation may be sufficiently improved using a hybrid assay combining two antibodies with specificities that complement each other. Two monoclonal antibodies (mAb) with broad but different specificities towards sulfonamides were examined for their binding to a panel of hapten conjugates. MAb - hapten pairs without mutual cross-reactions were identified, and classical direct antigen-coated and mAb-coated ELISAs were developed as formats with referent specificities...
March 13, 2018: Analytical Chemistry
David A Rafei-Shamsabadi, Saskia van de Poel, Britta Dorn, Stefanie Kunz, Stefan F Martin, Christoph S N Klose, Sebastian J Arnold, Yakup Tanriver, Karolina Ebert, Andreas Diefenbach, Timotheus Y F Halim, Andrew N J McKenzie, Thilo Jakob
Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of TNCB-induced CHS using EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice. Ear swelling responses, cutaneous ILC numbers and cytokine production were determined at different time points. Functional analyses were performed in a CD90...
March 8, 2018: Journal of Investigative Dermatology
Hajime Suto, Aya Nambu, Hideaki Morita, Sachiko Yamaguchi, Takafumi Numata, Takamichi Yoshizaki, Eri Shimura, Ken Arae, Yousuke Asada, Kenichiro Motomura, Mari Kaneko, Takaya Abe, Akira Matsuda, Yoichiro Iwakura, Ko Okumura, Hirohisa Saito, Kenji Matsumoto, Katsuko Sudo, Susumu Nakae
BACKGROUND: As well as thymic stromal lymphopoietin (TSLP) and IL-33, IL-25 is known to induce Th2 cytokine production by various cell types-including Th2 cells, Th9 cells, invariant NKT cells and group 2 innate lymphoid cells-involved in Th2-type immune responses. Since both Th2-type and Th17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 may contribute to this by enhancing Th2-type immune responses. However, the precise role of IL-25 in the pathogenesis of FITC-induced CHS is poorly understood...
March 6, 2018: Journal of Allergy and Clinical Immunology
Zhibin Liang, Qing X Li
The π-cation interaction that differs from the cation-π interaction is a valuable concept in molecular design of pharmaceuticals and pesticides. In this Perspective we present an up-to-date review (from 1995 to 2017) on bioactive molecules involving π-cation interactions with the recognition site, and categorize into systems of inhibitor-enzyme, ligand-receptor, ligand-transporter, and hapten-antibody. The concept of π-cation interactions offers use of π systems in a small molecule to enhance the binding affinity, specificity, selectivity, lipophilicity, bioavailability, and metabolic stability, which are physiochemical features desired for drugs and pesticides...
March 9, 2018: Journal of Agricultural and Food Chemistry
Marie J Ducrotoy, Pilar M Muñoz, Raquel Conde-Álvarez, José M Blasco, Ignacio Moriyón
Brucellosis is a worldwide extended zoonosis with a heavy economic and public health impact. Cattle, sheep and goats are infected by smooth Brucella abortus and Brucella melitensis, and represent a common source of the human disease. Brucellosis diagnosis in these animals is largely based on detection of a specific immunoresponse. We review here the immunological tests used for the diagnosis of cattle brucellosis. First, we discuss how the diagnostic sensitivity (DSe) and specificity (DSp), balance should be adjusted for brucellosis diagnosis, and the difficulties that brucellosis tests specifically present for the estimation of DSe/DSp in frequentistic (gold standard) and Bayesian analyses...
March 1, 2018: Preventive Veterinary Medicine
Orapin Udomsin, Supaluk Krittanai, Tharita Kitisripanya, Hiroyuki Tanaka, Waraporn Putalun
Background: Puerarin (PUE) is a phytoestrogen found in Pueraria candollei and Pueraria lobata. These plants are substantial for traditional medicine in various Asian countries. PUE is a key marker that can be found only in the Pueraria species. Objective: To establish the method for determination of PUE content which is required for quality control of pharmaceutical products. Materials and Methods: PUE-cationized bovine serum albumin conjugate was created via Mannich reaction...
January 2018: Pharmacognosy Magazine
Kai Yao, Kai Wen, Wenchong Shan, Sanlei Xie, Tao Peng, Jianyi Wang, Haiyang Jiang, Bing Shao
An immunoaffinity clean-up material based on a monoclonal antibody (mAb) has been prepared for concentrating and purifying bisphenol A (BPA) in 14 kinds of foodstuffs at trace level. Haptens and immunogen of bisphenol A have been synthesized and comprehensively characterized. An mAb towards BPA was prepared and cross-reactivities with 14 BPA analogues were below 5%. The prepared antibody was coupled to N-hydroxysuccinimide-activated Sepharose 4B to manufacture an immunoaffinity column (IAC), which was applied to purify BPA in 14 kinds of foodstuffs...
February 13, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Congmin Liu, Xiaowen Dou, Lei Zhang, Weijun Kong, Liu Wu, Yaping Duan, Meihua Yang
In the present study, molecular modeling and principle component analysis (PCA) were used to select appropriate haptens for group detection of triazine herbicides. Four new structures together with three reported triazine derivatives were chosen for the screening of immunizing and coating haptens. A total of 31 triazines coupled with a 3D-QSAR methodology were employed to investigate the relationship between antigen-antibody recognition and molecular structures, the results of which revealed that the antibodies may recognize triazines from the side of molecules with the distinguishing atom and a steric volume matching with the spatial structure of antibodies...
July 5, 2018: Analytica Chimica Acta
Daan Dittmar, Wolfgang Uter, Andrea Bauer, Anna B Fortina, Andreas J Bircher, Magdalena Czarnecka-Operacz, Aleksandra Dugonik, Peter Elsner, Rosella Gallo, Sharizan A Ghaffar, Anna Giménez-Arnau, Graham A Johnston, Beata Kręcisz, Francesca L Filon, Thomas Rustemeyer, Anna Sadowska-Przytocka, Javier Sánchez-Pérez, Axel Schnuch, Dagmar Simon, Radoslaw Spiewak, Philipp Spring, Maria T Corradin, Skaidra Valiukevičienė, Marko Vok, Elke Weisshaar, Mark Wilkinson, Marie L Schuttelaar
BACKGROUND: Polysensitization, defined as being allergic to three or more haptens from the European baseline series, is considered to reflect increased susceptibility to developing a contact allergy, and is likely to be associated with an impaired quality of life. OBJECTIVES: To evaluate the prevalences of polysensitization across Europe and to analyse factors associated with polysensitization. METHODS: Patch test data collected by the European Surveillance System on Contact Allergies (ESSCA; www...
February 22, 2018: Contact Dermatitis
Daniela Schmid, Annette Buntz, Thi Ngoc Hanh Phan, Klaus Mayer, Eike Hoffmann, Irmgard Thorey, Jens Niewöhner, Katrin Vasters, Ranjan Sircar, Olaf Mundigl, Roland E Kontermann, Ulrich Brinkmann
A transcellular shuttle system was generated for delivery of non-covalently linked payloads across blood-brain-barrier (BBB) endothelial cells. Transcytosis enabling shuttles are composed of bispecific antibodies (bsAbs) that simultaneously bind transferrin receptor (TfR) and haptens such as digoxigenin or biocytinamide. Haptenylated payloads are attached to these vehicles via non-covalent hapten-antibody complexation. This enables targeting to and internalization into human BBB-derived microvascular endothelial HCMEC/D3 cells...
December 20, 2017: Biological Chemistry
Fuyuan Zhang, Bing Liu, Guozhen Liu, Yan Zhang, Junping Wang, Shuo Wang
Based on the structural features of fluometuron, an immunizing hapten was synthesized and conjugated to bovine serum albumin as an immunogen to prepare a polyclonal antibody. However, the resultant antibody indicated cross-reactivity with 6 structurally similar phenylurea herbicides, with binding activities (expressed by IC 50 values) ranging from 1.67 µg/L to 42.71 µg/L. All 6 phenylurea herbicides contain a common moiety and three different substitutes. To understand how these three different chemical groups affect the antibody-phenylurea recognition activity, quantum chemistry, using density function theory (DFT) at the B3LYP/6-311++ G(d,p) level of theory, was employed to optimize all phenylurea structures, followed by determination of the 3D conformations of these molecules, pharmacophore analysis, and molecular electrostatic potential (ESP) analysis...
February 15, 2018: Scientific Reports
Isabella Karlsson, Kristin Samuelsson, Carl Simonsson, Anna-Lena Stenfeldt, Ulrika Nilsson, Leopold L Ilag, Charlotte Jonsson, Ann-Therese Karlberg
Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system...
February 13, 2018: Scientific Reports
Zoltan Beck, Oscar B Torres, Gary R Matyas, David E Lanar, Carl R Alving
Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA)...
February 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xiaoli Meng, Zaid Al-Attar, Fiazia S Yaseen, Rosalind Jenkins, Caroline Earnshaw, Paul Whitaker, Daniel Peckham, Neil S French, Dean J Naisbitt, B Kevin Park
No abstract text is available yet for this article.
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Andrew Gibson, Lee Faulkner, Maike Lichtenfels, Monday Ogese, Zaid Al-Attar, Ana Alfirevic, Philipp R Esser, Stefan F Martin, Munir Pirmohamed, B Kevin Park, Dean J Naisbitt
No abstract text is available yet for this article.
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Qizhao Huang, Haoqiang Wang, Lifan Xu, Jianjun Hu, Pengcheng Wang, Yiding Li, Lilin Ye
B lymphocytes and their differentiated daughter cells are charged with responding to invading pathogens and producing protective antibodies against these pathogens. The physiology of B cells is intimately connected with the function of the B cell antigen receptor (BCR). Upon activation of BCR, transmembrane signals are generated, and several downstream pathways are activated, which provide a primary directive for the cell's subsequent response. mTOR is a serine/threonine kinase that controls cell proliferation and metabolism in response to a diverse range of extracellular stimuli...
2018: Methods in Molecular Biology
Yasuyuki Fujimoto, Takashi Fujita, Nobuyuki Kuramoto, Mitsuru Kuwamura, Takeshi Izawa, Kazuhiro Nishiyama, Natsuho Yoshida, Hidemitsu Nakajima, Tadayoshi Takeuchi, Yasu-Taka Azuma
Interleukin (IL)-19 is a member of the IL-10 family of interleukins and is an immuno-modulatory cytokine produced by the main macrophages. The gastrointestinal tissues of IL-19 knockout mice show exacerbated experimental colitis mediated by the innate immune system and T cells. There is an increasing focus on the interaction and relationship of IL-19 with the function of T cells. Contact hypersensitivity (CHS) is T cell-mediated cutaneous inflammation. Therefore, we asked whether IL-19 causes CHS. We investigated the immunological role of IL-19 in CHS induced by 1-fluoro-2,4-dinitrofluorobenzene as a hapten...
2018: Biological & Pharmaceutical Bulletin
Karen M Haas, Kristen L Johnson, James P Phipps, Cardinal Do
CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22-/- mice generate significantly impaired Ab responses to T cell-independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22-/- mice. However, mice expressing a mutant form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab responses, despite significantly reduced MZ B cells...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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