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https://www.readbyqxmd.com/read/28709828/augmenting-the-efficacy-of-anti-cocaine-catalytic-antibodies-through-chimeric-hapten-design-and-combinatorial-vaccination
#1
Cody J Wenthur, Xiaoqing Cai, Beverly A Ellis, Kim D Janda
Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28705917/curative-multi-cycle-radioimmunotherapy-monitored-by-quantitative-spect-ct-based-theranostics-using-bispecific-antibody-pretargeting-strategy-in-colorectal-cancer
#2
Sarah M Cheal, Edward K Fung, Miteshkumar V Patel, Blesida Punzalan, Hong Xu, Hong-Fen Guo, Pat B Zanzonico, Sebastien Monette, Karl Dane Wittrup, Nai-Kong Cheung, Steven M Larson
Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been limited by low therapeutic indices (TI). We recently reported a novel three-step pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)-targeting bispecific antibody (bsAb) and a small-molecule radioactive hapten, a complex of lutetium-177 ((177)Lu) and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid ((177)Lu-DOTA-Bn) that leads to high TIs for radiosensitive tissues such as blood (TI = 73) and kidney (TI = 12)...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28695412/-basis-for-the-treatment-of-eczematous-diseases-in-otorhinolaryngology
#3
REVIEW
R Fölster-Holst, A Sperl, T Albrecht, L Klimek
According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. In otorhinolaryngology, delayed allergic hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis, auricle and ear canal eczema as well as perioral eczema belong to the most common forms of contact dermatitis in ENT patients...
July 10, 2017: HNO
https://www.readbyqxmd.com/read/28688361/a-survey-of-17%C3%AE-ethinylestradiol-and-mestranol-residues-in-hawkesbury-river-australia-using-a-highly-specific-enzyme-linked-immunosorbent-assay-elisa-demonstrates-the-levels-of-potential-biological-significance
#4
Chatchaporn Uraipong, Robin D Allan, Chunhua Li, Ivan R Kennedy, Victor Wong, Nanju Alice Lee
This study reports on the potential status of 17α-ethinylestradiol (EE2) and mestranol (MeEE2) residues in aquatic environments in New South Wales (NSW), Australia, based on the analysis by a specific ELISA we developed. Polyclonal antibodies were raised against the EE2 hapten with a linker attached at the C3-position to direct the antibody binding towards the ring D of EE2/MeEE2. Using this approach, an ELISA highly specific to EE2 and MeEE2 was successfully developed, showing less than 3.1% cross-reactivity (% CR) with other major steroidal sex hormones and their derivatives...
July 5, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28687658/the-effect-of-inhibitory-signals-on-the-priming-of-drug-hapten-specific-t-cells-that-express-distinct-v%C3%AE-receptors
#5
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
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28687491/site-specific-regulation-of-oral-mucosa-recruiting-cd8-t-cells-in-a-mouse-contact-allergy-model
#6
Worawalun Hirunwidchayarat, Emi Furusawa, Siwen Kang, Tatsukuni Ohno, Shunsuke Takeuchi, Sorasun Rungsiyanont, Miyuki Azuma
Contact allergy is a T cell-mediated, delayed-type hypersensitivity generated by contact exposure of an allergen to the skin and mucosal surface. The clinical manifestations of allergic responses between the skin and oral mucosa vary and the differences in immunopathology have not been clarified. We generated hapten-induced contact hypersensitivity (CH) of the buccal mucosa (BM) in parallel studies with ear skin (ES) CH, and observed several characteristic findings of BM CH. The BM challenge induced more rapid and more severe inflammation than the ES challenge, with abundant granulocyte and CD8(+) T cell infiltration...
July 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28670256/contact-allergy-in-the-population-of-patients-with-chronic-inflammatory-dermatoses-and-contact-hypersensitivity-to-corticosteroids
#7
Marek Kot, Jarosław Bogaczewicz, Beata Kręcisz, Anna Woźniacka
INTRODUCTION: Clinical studies indicate that contact allergy to glucocorticosteroids (GCS) is not rare and has been increasingly reported over the past decade. Among the risk factors for developing contact hypersensitivity to topical corticosteroids, chronic inflammatory skin diseases and polyvalent contact allergy seem to be most important. AIM: To present the structure of contact allergy in the population of patients with chronic inflammatory dermatoses (CID) and contact hypersensitivity to corticosteroids...
June 2017: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28667471/topical-application-of-dermatophagoides-farinae-or-oxazolone-induces-symptoms-of-atopic-dermatitis-in-the-rabbit-ear
#8
Jingling Zhao, Shengxian Jia, Ping Xie, Gabriel A Arenas, Robert D Galiano, Seok Jong Hong, Thomas A Mustoe
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the epidermis, and dermal infiltration of inflammatory cells. Appropriate animal models that recapitulate human AD and allow the analysis of disease processes in a reliable manner are essential to the study of AD. In this study, we established two AD models in rabbits by applying an allergen, Dermatophagoides farinae (Der f), or a hapten, oxazolone (OXZ). Application of the allergen or hapten induced a rapid onset and a chronically sustained AD-like skin lesion...
June 30, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28634286/conjugate-vaccine-immunotherapy-for-substance-use-disorder
#9
REVIEW
Paul T Bremer, Kim D Janda
Substance use disorder, especially in relation to opioids such as heroin and fentanyl, is a significant public health issue and has intensified in recent years. As a result, substantial interest exists in developing therapeutics to counteract the effects of abused drugs. A promising universal strategy for antagonizing the pharmacology of virtually any drug involves the development of a conjugate vaccine, wherein a hapten structurally similar to the target drug is conjugated to an immunogenic carrier protein...
July 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28629263/mass-spectrometry-based-analysis-of-murine-bronchoalveolar-lavage-fluid-following-respiratory-exposure-to-4-4-methylene-diphenyl-diisocyanate-aerosol
#10
Justin M Hettick, Brandon F Law, Chen-Chung Lin, Adam V Wisnewski, Paul D Siegel
Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products, and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI)...
June 20, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28629026/multistate-proteinous-biomemory-device-based-on-redox-controllable-hapten-cross-linker
#11
Remziye Güzel, Arzu Ersöz, İbrahim Dolak, Rıdvan Say
A multistate biomemory device consisting of cytochrome c (Cyt-c) photosensitively cross-linked by MACys-Ru(bipyr)2-MACys hapten molecules, which have memory effect through a charge transfer mechanism, has been developed. In this study, it has suggested a highly resolute surface-confined switch composed a signal-enhanced electro-active protein (Cyt-c) co-polymerized on the gold substrates that can be controlled by redox property through Ruthenium based cysteine monomer hapten, MACys-Ru(bipyr)2-MACys as an ANADOLUCA photosensitive cross-linker...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28622663/sensitive-immunoassay-for-simultaneous-determination-of-tetrabromobisphenol-a-bis-2-hydroxyethyl-ether-and-tetrabromobisphenol-a-mono-hydroxyethyl-ether-an-effective-and-reliable-strategy-to-estimate-the-typical-tetrabromobisphenol-a-derivative-and-byproduct
#12
Zhen Zhang, Nuanfei Zhu, Menglu Huang, Yaru Liang, Kun Zeng, Xiangyang Wu, Zhenjiang Liu, Qianchi Ma, Guangbo Qu, Jianbo Shi
Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA DHEE), as one of the TBBPA derivatives, is frequently applied as a flame retardant. To date, however, little evidence has been gathered regarding its environmental behavior and fate. This is mainly attributed to the lack of an analytical approach available to measure it. Mass spectrometry cannot determine levels of TBBPA DHEE. LC-MS could not ionize TBBPA DHEE to yield enough fragments, while GC-MS could not be applied for the analysis either, due to the thermal degradation of TBBPA DHEE...
June 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28611939/selective-targeting-of-the-l858r-mutation-egfr-in-non-small-cell-lung-cancer-a-mechanism-for-advancing-targeted-chemotherapy
#13
Rohan Arora, Venkat Krishnan
Lung cancer remains one of today's most deadly and intractable cancers. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancers, with an extremely poor survival rate. To ensure patient comfort and survival, the development of a selective therapy is imperative. However, lung cancer does not display surface proteins associated uniquely with tumor cells; thus, it is very difficult to develop a tumor-specific drug. Current techniques that target overexpression of proteins or inhibit growth pathways are either non-specific or prone to rapid drug resistance...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28605688/enzyme-less-electrochemical-displacement-heterogeneous-immunosensor-for-diclofenac-detection
#14
T T K Nguyen, T T Vu, G Anquetin, H V Tran, S Reisberg, V Noël, G Mattana, Q V Nguyen, Tran Dai Lam, M C Pham, B Piro
We describe an electrochemical immunosensor based on functionalization of a working electrode by electrografting two functional diazonium salts. The first one is a molecular probe, diclofenac, coupled with an arylamine onto which a specific antibody is immobilized by affinity interactions; the second is a redox probe (a quinone) also coupled with an arylamine, able to transduce the hapten-antibody association into a change in electroactivity. The steric hindrance induced by the antibody leads to a current decrease upon binding of the antibody on the grafted molecular probe; conversely, when diclofenac is present in solution, a displacement equilibrium occurs between the target diffusing into the solution and the grafted probe...
June 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28603847/tight-molecular-recognition-of-benzo-a-pyrene-by-a-high-affinity-antibody
#15
Andreas Eichinger, Irmgard Neumaier, Michael Pschenitza, Reinhard Nießner, Dietmar Knopp, Arne Skerra
Benzo[a]pyrene, produced during the combustion of organic material, is an abundant noxious pollutant because of its carcinogenic metabolic degradation products. The high affinity (KD ≈ 3 nM) monoclonal antibody 22F12 allows facile bioanalytical quantification of benzo[a]pyrene even in complex matrices. Here, we report its functional and X-ray crystallographic analysis in complex with 3-hydroxybenzo[a]pyrene after cloning of the V-genes and production as a recombinant Fab fragment. The polycyclic aromatic hydrocarbon is bound in a deep pocket beween the light and heavy chains surrounded mainly by aromatic and aliphatic amino acid side chains...
June 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28602621/binary-test-battery-with-keratinosens%C3%A2-and-h-clat-as-part-of-a-bottom-up-approach-for-skin-sensitization-hazard-prediction
#16
Yuki Otsubo, Taku Nishijo, Masaaki Miyazawa, Kazutoshi Saito, Hideyuki Mizumachi, Hitoshi Sakaguchi
Skin sensitization is one of the key safety endpoints for chemicals applied directly to the skin. Several integrated testing strategies (ITS) using multiple non-animal test methods have been developed to accurately evaluate the sensitizing potential of chemicals, but there is no regulatory-accepted ITS to classify a chemical as a non-sensitizer. In this study, the predictive performance of a binary test battery with KeratinoSens™ and h-CLAT compared to the local lymph node assay (LLNA) and human data was examined using comprehensive dataset of 203 chemicals...
June 7, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28598600/protein-free-hapten-carbon-nanotube-constructs-induce-the-secondary-immune-response
#17
Eric Ceballos-Alcantarilla, Antonio Abad-Somovilla, Consuelo Agulló, Antonio Abad-Fuentes, Josep V Mercader
Carbon nanotubes are novel technological tools with multiple applications. The interaction between such nanoparticles and living organisms is nowadays a matter of keen research by academic and private institutions. In this study, carbon nanotube constructs were investigated as delivery vehicles for immunostimulation and induction of the secondary immune response to a small organic molecule, namely, a hapten. Two types of nanoconstructs were prepared: on one hand, carbon nanotubes carrying a protein bioconjugate of a hapten covalently linked to the carbon surface, and on the other hand, covalent carbon nanotube constructs of the same model chemical compound without the carrier protein...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28589358/somatic-hypermutation-and-affinity-maturation-analysis-using-the-4-hydroxy-3-nitrophenyl-acetyl-np-system
#18
Nicole Heise, Ulf Klein
Somatic hypermutation of immunoglobulin variable region (IgV) genes and affinity maturation of the antibody response are the hallmarks of the germinal center (GC) reaction in T cell-dependent immune responses. Determining the consequences of the experimental manipulation of the GC response on somatic hypermutation and affinity maturation requires the availability of a system that allows measuring these parameters. Immunization of mice of the C57/Bl6 genetic background with the hapten 4-hydroxy-3-nitrophenyl-acetyl (NP) coupled to a carrier protein leads to the predominant usage of one particular IgV heavy chain gene segment, V186...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28583370/prostaglandin-e2-stimulates-adaptive-il-22-production-and-promotes-allergic-contact-dermatitis
#19
Calum T Robb, Henry J McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M Felton, Nicholas Parkinson, Adane Ayele, Richard M Breyer, Stephen M Anderton, Shuh Narumiya, Adriano G Rossi, Sarah E Howie, Emma Guttman-Yassky, Richard B Weller, Chengcan Yao
BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of Th22-derived IL-22 in their pathogenesis. Although prostaglandin E2 (PGE2) is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 up-regulation. OBJECTIVES: To investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD...
June 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28574716/development-of-a-clinically-viable-heroin-vaccine
#20
Paul T Bremer, Joel E Schlosburg, Matthew L Banks, Floyd F Steele, Bin Zhou, Justin L Poklis, Kim D Janda
Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin "immunoantagonism", reducing heroin potency by >15-fold...
June 20, 2017: Journal of the American Chemical Society
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