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https://www.readbyqxmd.com/read/29150704/evaluation-of-immune-mediated-idiosyncratic-drug-toxicity-using-chimeric-hla-transgenic-mice
#1
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29149705/toll-like-receptor-4-deficiency-increases-resistance-in-sepsis-induced-immune-dysfunction
#2
Chao Cao, Yanfen Chai, Songtao Shou, Jun Wang, Ying Huang, Tao Ma
Sepsis constitutes a serious life-threatening syndrome associated with complications of deregulated inflammatory response against endotoxin/lipopolysaccharide (LPS)-mediated severe infection. Toll-like receptor 4 (TLR4) plays a critical role in the activation of innate immunity through recognition of LPS. However, the impact of TLR4 signaling on the development of sepsis-induced immune dysfunction remains unclear. The aim of this study was to investigate the effect of TLR4 on regulatory T cells (Tregs) and its potential mechanism...
November 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#3
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146495/polysaccharides-from-citrus-grandis-l-osbeck-suppress-inflammation-and-relieve-chronic-pharyngitis
#4
Liyan Chen, Yongfeng Lai, Lei Dong, Shasha Kang, Xiumei Chen
Chronic pharyngitis, a common inflammation of the pharyngeal mucosa, is often caused by bacteria, viruses, alcohol abuse, overuse of the voice and cigarettes. This study aimed to explore the effects of polysaccharides of Citrus grandis L. Osbeck (PCG) in relieving chronic pharyngitis and illustrate the underlying mechanisms. Polysaccharides were obtained from PCG by column chromatographic extraction. Six clinical symptom scores, such as the severity of itchy throat, hoarseness, pain, odynophagia, cough and otalgia were evaluated in chronic pharyngitis patients after the oral intake of PCG...
November 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29145965/increased-cytokine-levels-and-histological-changes-in-cartilage-synovial-cells-and-synovial-fluid-after-malleolar-fractures
#5
Alexandre L Godoy-Santos, Lucas Ranzoni, Walcy R Teodoro, Vera Capelozzi, Pedro Giglio, Tulio Diniz Fernandes, Stefan Rammelt
BACKGROUND: Malleolar fractures are among the most common fractures in the human skeleton with a high risk of later development of post-traumatic osteoarthritis (OA). The acute ankle injury initiates a sequence of events potentially leading to progressive articular surface damage resulting from inflammatory changes in cartilage, synovial tissue and synovial fluid. We hypothesised that in the acute phase of ankle fracture, these changes occur at the same time in the different tissues. METHODS: Specimens of chondral tissue, synovial tissue and synovial fluid were collected from 16 patients with acute articular ankle fracture (study group)...
October 2017: Injury
https://www.readbyqxmd.com/read/29145467/adenosine-lidocaine-and-mg2-alm-fluid-therapy-attenuates-systemic-inflammation-platelet-dysfunction-and-coagulopathy-after-non-compressible-truncal-hemorrhage
#6
Hayley Letson, Geoffrey Dobson
BACKGROUND: Systemic inflammation and coagulopathy are major drivers of injury progression following hemorrhagic trauma. Our aim was to examine the effect of small-volume 3% NaCl adenosine, lidocaine and Mg2+ (ALM) bolus and 0.9% NaCl/ALM 'drip' on inflammation and coagulation in a rat model of hemorrhagic shock. METHODS: Sprague-Dawley rats (429±4 g) were randomly assigned to: 1) shams, 2) no-treatment, 3) saline-controls, 4) ALM-therapy, and 5) Hextend®. Hemorrhage was induced in anesthetized-ventilated animals by liver resection (60% left lateral lobe and 50% medial lobe)...
2017: PloS One
https://www.readbyqxmd.com/read/29144585/therapeutic-potential-of-low-dose-il-2-in-immune-thrombocytopenia-an-analysis-of-3-cases
#7
Jiakui Zhang, Yanjie Ruan, Xuanxuan Xu, Huiping Wang, Qianshan Tao, Jun Lu, Linhuan Xia, Qiuye Zhang, Jeffrey Wang, Yiping Wang, Zhimin Zhai
Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder with regulatory T cells (Tregs) reduction. Recent studies have shown that low-dose interleukin-2 can preferentially induce regulatory T cell expansion in vivo, and therefore offers a therapeutic strategy against immune thrombocytopenia. We have demonstrated in a previous study that Tregs and platelet counts significantly improve in an adult with ITP following low-dose IL-2 treatment. Here we report the efficacy of low-dose interleukin-2 in another three adults with immune thrombocytopenia who failed the first-line treatment...
November 16, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29142605/aviscumine-a-recombinant-ribosomal-inhibitor-increases-the-antitumor-activity-of-natural-killer-cells
#8
Gabriele Gamerith, Arno Amann, Bettina Schenk, Thomas Auer, Hans Lentzen, Dirk O Mügge, Katharina M Cima, Judith Löffler-Ragg, Wolfgang Hilbe, Heinz Zwierzina
Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142417/inhibition-of-phosphorylated-c-jun-nh-2-terminal-kinase-by-2-4-dihydroxy-6-methoxy-3-5-dimethylchalcone-isolated-from-eugenia-aquea-burm-f-leaves-in-jurkat-t-cells
#9
Melisa I Barliana, Ajeng Diantini, Anas Subarnas, Rizky Abdulah, Takashi Izumi
Background: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted considerable attention. Our previous study found that 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone, an active compound isolated from leaves of Indonesian medicinal plants Eugenia aquea Burm f...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#10
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141157/the-devastating-effect-of-exposure-to-high-irradiation-dose-on-liver-and-the-performance-of-synthesized-nano-hap-in-relieve-the-associated-symptoms-in-rats
#11
Eman Ismail Gheriany, Sameh A Awwad
Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction by a mechanism involving oxidative stress. The present investigation was undertaken to study the possible therapeutic effect of nano-HAp on whole body gamma irradiation induced hepatotoxicity in rats. The study consisted of three groups of 10 rats each. Group 1 (control), whereas group 2 received a single dose of γ-radiation (10Gy). The animals in groups 3 was treated with nano-HAp (100 mg/kg b.w.) once / week for three weeks starting in the next day of γ radiation...
November 15, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29140228/co-factor-independent-phosphoglycerate-mutase-of-leishmania-donovani-modulates-macrophage-signalling-and-promotes-t-cell-repertoires-bearing-epitopes-for-both-mhc-i-and-mhc-ii
#12
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
https://www.readbyqxmd.com/read/29138220/antibodies-targeting-surface-membrane-antigens-in-patients-with-chronic-graft-versus-host-disease
#13
Kathy S Wang, Haesook T Kim, Sarah Nikiforow, Alexander T Heubeck, Vincent T Ho, John Koreth, Edwin P Alyea, Philippe Armand, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Corey S Cutler, Jerome Ritz
Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) reflects a complex immune response resulting in chronic damage to multiple tissues. Previous studies indicated that donor B cells and the antibodies they produce play an important role in the development of cGVHD. To understand the pathogenic role of antibodies in cGVHD, we focused our studies on post-transplant production of IgG antibodies targeting cell surface antigens expressed in multiple cGVHD affected tissues, due to their potential functional impact on living cells in vivo...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29133633/altered-tear-inflammatory-profile-in-indian-keratoconus-patients-the-2015-col-rangachari-award-paper
#14
Rohit Shetty, Rashmi Deshmukh, Arkasubhra Ghosh, Swaminathan Sethu, Chaitra Jayadev
PURPOSE: Conventionally, keratoconus (KC) has been considered a noninflammatory corneal ectatic disorder. Recent evidence suggests a possible role of inflammation in the pathogenesis of KC. Hence, we analyzed the levels of inflammatory factors in the tear fluid of Indian KC patients. METHODS: Tear fluid samples were collected from age- and sex-matched healthy controls and KC patients (with different grades). The levels of the inflammatory factors in tears were analyzed using cytometric bead array (Human Soluble Protein Flex Set System, BD Biosciences) for levels of interleukin-1α (IL-1α), IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12p70, IL-23p40, IL-13, IL-17A, IL-17F, IL-21, interferon-α (IFNα), IFNγ, tumor necrosis factor-α, CCL2/monocyte chemotactic protein-1, CCL4/macrophage inflammatory protein-1β (MIP-1β), MIP-1α, CCL5/RANTES, CXCL10/IP10, ICAM1, CD62E, vascular endothelial growth factor and transforming growth factor β...
November 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29133346/mycobacterium-tuberculosis-groel2-modulates-dendritic-cell-responses
#15
Maria Georgieva, Jonathan Kevin Sia, Erica Bizzell, Ranjna Madan-Lala, Jyothi Rengarajan
Mycobacterium tuberculosis (Mtb) successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, Mtb interferes with the functions of dendritic cells (DCs), which are the primary antigen presenting cells in the immune system. We previously showed that Mtb dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease, Hip1. Here we present data showing that Mtb GroEL2, a substrate of Hip1, modulates DC functions...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29132960/influenza-derived-peptides-cross-react-with-allergens-and-provide-asthma-protection
#16
Chrysanthi Skevaki, Christoph Hudemann, Mikhail Matrosovich, Christian Möbs, Sinu Paul, Andreas Wachtendorf, Bilal Alashkar Alhamwe, Daniel P Potaczek, Stefanie Hagner, Diethard Gemsa, Holger Garn, Alessandro Sette, Harald Renz
BACKGROUND: The hygiene hypothesis is the leading concept to explain the current asthma epidemic, which is built on the observation that a lack of bacterial contact early in life induces allergic Th2 immune responses. OBJECTIVE: Since little is known about the contribution of respiratory viruses in this context, we evaluated the effect of prior influenza-infection on the development of allergic asthma. METHODS: Mice were infected with influenza and once recovered, subjected to an ovalbumin or house dust mite-induced experimental asthma protocol...
November 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29131274/expression-level-and-clinical-significance-of-il-2-il-6-and-tgf-%C3%AE-in-elderly-patients-with-goiter-and-hyperthyroidism
#17
L-F Lv, H-Y Jia, H-F Zhang, Y-X Hu
OBJECTIVE: To investigate the level of expression and the clinical significance of IL-2 (interleukin-2), IL-6 (interleukin-6) and TGF-β (transforming growth factor-β) in elderly patients with goiter and hyperthyroidism. PATIENTS AND METHODS: Gender, age, course of disease, BMI (Body Mass Index), serum FT3 (Free triiodothyronine-3), FT4 (Free triiodothyronine-4), TT3 (Total triiodothyronine-3), TT4 (Total triiodothyronine-4), TSH (Thyroid Stimulating Hormone) and clinical manifestations on admission and other general clinical data and laboratory examination results were collected and statistically analyzed as case group in 128 elderly patients with goiter and hyperthyroidism...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29129929/il-2-imprints-human-naive-b-cell-fate-towards-plasma-cell-through-erk-elk1-mediated-bach2-repression
#18
Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, Karin Tarte, Thierry Fest, Céline Delaloy
Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129453/hepatitis-b-virus-core-particles-containing-multiple-epitopes-confer-protection-against-enterovirus-71-and-coxsackievirus-a16-infection-in-mice
#19
Chunling Huo, Jie Yang, Lei Lei, Lei Qiao, Jiantao Xin, Zishu Pan
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand-foot-and-mouth disease (HFMD). To investigate novel combined vaccines to prevent EV71 and CA16 infection, we constructed chimeric virus-like particles (tHBc/SPA or tHBc/SP VLPs) displaying conserved epitopes of EV71 (aa 208-222 of VP1 and aa 248-263 of VP2) and CA16 (aa271-285 of VP1) using a truncated hepatitis B virus core carrier (tHBc). Immunization with the chimeric VLPs induced epitope- or virus-specific IgG and neutralization antibodies against EV71 and CA16 in the mice...
November 9, 2017: Vaccine
https://www.readbyqxmd.com/read/29127148/ubc9-binds-to-adap-and-is-required-for-rap1-membrane-recruitment-rac1-activation-and-integrin-mediated-t-cell-adhesion
#20
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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