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Tolerance induction

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https://www.readbyqxmd.com/read/29352109/role-of-b-and-t-lymphocyte-attenuator-in-renal-transplant-recipients-with-biopsy-proven-acute-rejection
#1
Zijie Wang, Haiwei Yang, Xuzhong Liu, Jingying Zhang, Zhijian Han, Jun Tao, Chunchun Zhao, Xiaobin Ju, Ruoyun Tan, Min Gu
BACKGROUND Acute rejection is a common predisposing cause of allograft dysfunction in kidney transplantation. Recently, the B and T lymphocyte attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160 pathway was found to be potentially involved in the regulation of T cell activation. This could mean that this pathway is involved in graft rejection in kidney transplantation; the present study aimed to explore this possibility. MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients with biopsy-proven acute rejection (BPAR) or stable allograft function, as well as in healthy volunteers...
January 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29351550/differential-actions-of-ppar-%C3%AE-and-ppar-%C3%AE-%C3%AE-on-beige-adipocyte-formation-a-study-in-the-subcutaneous-white-adipose-tissue-of-obese-male-mice
#2
Tamiris Lima Rachid, Flavia Maria Silva-Veiga, Francielle Graus-Nunes, Isabele Bringhenti, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29348128/pevonedistat-a-first-in-class-nedd8-activating-enzyme-nae-inhibitor-combined-with-azacitidine-in-patients-with-aml
#3
Ronan T Swords, Steven Coutre, Michael B Maris, Joshua F Zeidner, James M Foran, Jose Cruz, Harry P Erba, Jesus G Berdeja, Wayne Tam, Saran Vardhanabhuti, Iwona Pawlikowska-Dobler, Hélène M Faessel, Ajeeta B Dash, Farhad Sedarati, Bruce J Dezube, Douglas V Faller, Michael R Savona
Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study (NCT01814826) of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naïve AML, unfit for standard induction therapy, received PEV 20 or 30 mg/m2 IV on days 1, 3, and 5, combined with fixed-dose AZA (75 mg/m2 IV/SC) on days 1-5, 8, and 9, every 28 days...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29345052/hpap-a-novel-regulatory-protein-with-atpase-and-phosphatase-activity-contributes-to-full-virulence-in-xanthomonas-campestris-pv-campestris
#4
Ping Cui, Rui-Fang Li, Da-Pei Zhang, Ji-Liang Tang, Guang-Tao Lu
The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on the type III secretion system (T3SS). Proteins of the Xcc T3SS are encoded by hrp (hypersensitive response and pathogenicity) genes and whose expression is mainly controlled by the regulators HrpG and HrpX. Here, we describe the identification and characterization of a previously unknown regulatory protein (named HpaP), which plays important role in hrp gene expression and virulence in Xcc...
January 18, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29343892/first-two-bilateral-hand-transplantations-in-india-part-4-immediate-post-operative-care-immunosuppression-protocol-and-monitoring
#5
Subramania Iyer, Mohit Sharma, P Kishore, Jimmy Mathew, R Janarthanan, Raghuveer Reddy, Abhijeet Wakure, Sundeep Vijayaraghavan, S M Chetan Mali, Visakh Varma, Ashish Chaudhari, Swapnil Dhake, Akshay Omkumar, George Kurian, Rajesh Nair, Anil Mathew, Zachariah Paul, Malini Eapen, Lalitha Biswas
Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC)...
May 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
https://www.readbyqxmd.com/read/29342467/boiling-and-pressure-cooking-impact-on-ige-reactivity-of-soybean-allergens
#6
Beatriz Cabanillas, Carmen Cuadrado, Julia Rodriguez, Maria Carmen Dieguez, Jesus F Crespo, Natalija Novak
BACKGROUND: Soybean is one of the 8 foods that causes the most significant rate of food allergies in the USA and Europe. Thermal processing may impact on the allergenic potential of certain foods. We aimed to investigate modifications of the IgE-binding properties of soybean proteins due to processing methods that have been previously found to impact on the allergenicity of legumes such as peanut. METHODS: Soybean seeds were subjected to different thermal processing treatments...
January 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29342187/induction-of-high-tolerance-to-artemisinin-by-sub-lethal-administration-a-new-in-vitro-model-of-p-falciparum
#7
Serena De Lucia, Ioannis Tsamesidis, Maria Carmina Pau, Kristina R Kesely, Antonella Pantaleo, Francesco Turrini
Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P...
2018: PloS One
https://www.readbyqxmd.com/read/29339782/loss-of-disease-tolerance-during-citrobacter-rodentium-infection-is-associated-with-impaired-epithelial-differentiation-and-hyperactivation-of-t-cell-responses
#8
Eugene Kang, Guangyan Zhou, Mitra Yousefi, Romain Cayrol, Jianguo Xia, Samantha Gruenheid
Citrobacter rodentium is an intestinal mouse pathogen widely used as a model to study the mucosal response to infection. Inbred mouse strains suffer one of two fates following infection: self-limiting colitis or fatal diarrheal disease. We previously reported that Rspo2 is a major genetic determinant of the outcome of C. rodentium infection; Rspo2 induction during infection of susceptible mice leads to loss of intestinal function and mortality. Rspo2 induction does not impact bacterial colonization, but rather, impedes the ability of the host to tolerate C...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#9
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29338551/the-regulatory-roles-of-b-cell-subsets-in-transplantation
#10
Zhulang Chu, Weilong Zou, Yanan Xu, Qiquan Sun, Yong Zhao
B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation...
January 17, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#11
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29336679/arcobacter-butzleri-ciprofloxacin-resistance-point-mutations-in-dna-gyrase-a-and-role-on-fitness-cost
#12
Susana Ferreira, Daniela R Correia, Mónica Oleastro, Fernanda C Domingues
Arcobacter butzleri is a widely distributed emerging pathogen resistant to various classes of antimicrobial agents, namely fluoroquinolones. A. butzleri resistance to fluoroquinolones is conferred by point mutations at the antibiotic target. The aim of this study was to evaluate mutations at gyrA associated with ciprofloxacin resistance and evaluate whether acquisition of resistance impacts on fitness and stress tolerance of A. butzleri. A. butzleri ciprofloxacin mutants were generated by laboratory induction...
January 16, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29334438/in-vitro-and-in-vivo-evaluations-of-the-anticalculus-effect-of-a-novel-stabilized-stannous-fluoride-dentifrice
#13
Tao He, Mary Kay Anastasia, Marianne Zsiska, Teresa Farmer, Eva Schneiderman, Jeffery L Milleman
OBJECTIVES: To evaluate the effect of a novel stannous fluoride dentifrice with zinc citrate on calculus inhibition using both in vitro and clinical models. METHODS: Each investigation tested a novel stabilized 0.454% stannous fluoride dentifrice with zinc citrate as an anticalculus agent (Crest® Pro-Health™ smooth formula) compared to a negative control fluoride dentifrice. The in vitro study used the modified Plaque Growth and Mineralization Model (mPGM). Plaque biofilms were prepared and mineralized by alternate immersion of glass rods in human saliva and artificial mineralization solution...
December 2017: Journal of Clinical Dentistry
https://www.readbyqxmd.com/read/29334375/a-small-molecule-inhibitor-of-the-ubiquitin-activating-enzyme-for-cancer-treatment
#14
Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S Amidon, Neil F Bence
The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29332329/modified-3-week-schedule-of-gemcitabine-plus-cisplatin-for-non-small-cell-lung-cancer-treatment
#15
Antonello Veccia, Viviana Murgia, Mariachiara Dipasquale, Orazio Caffo
PURPOSE: Gemcitabine-cisplatin combination is one of the most used schedules for non small cell lung cancer (NSCLC). Aiming to enhance dose intensity and reduce toxicity, the original 4-week schedule was modified or transformed into a 3-week schedule. The purpose of this study was to report the efficacy and tolerability of a modified 3-week regimen of gemcitabine-cisplatin. METHODS: Our patients were treated with gemcitabine (1000 mg7sol;m2) on days 1, 8 and cisplatin on day 8 (75-100 mg/m2)...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331760/inotodiol-suppresses-proliferation-of-breast-cancer-in-rat-model-of-type-2-diabetes-mellitus-via-downregulation-of-%C3%AE-catenin-signaling
#16
Xia Zhang, Cuiyu Bao, Jingping Zhang
Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 10 mg/kg...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29330772/rice-wrky11-plays-a-role-in-pathogen-defense-and-drought-tolerance
#17
Heyoung Lee, Jooyoung Cha, Changhyun Choi, Naeyoung Choi, Hyun-So Ji, Sang Ryeol Park, Seungbum Lee, Duk-Ju Hwang
BACKGROUND: Plants are frequently subjected to abiotic and biotic stresses, and WRKY proteins play a pivotal role in the response to such stress. OsWRKY11 is induced by pathogens, drought, and heat, suggesting a function in biotic and abiotic stress responses. RESULTS: This study identified OsWRKY11, a member of WRKY group IIc. It is a transcriptional activator that localized to the nucleus. Ectopic expression of OsWRKY11 resulted in enhanced resistance to a bacterial pathogen, Xanthomonas oryzae pv...
January 12, 2018: Rice
https://www.readbyqxmd.com/read/29330675/recognizing-conserved-non-canonical-localization-patterns-of-toll-like-receptors-in-tissues-and-across-species
#18
REVIEW
Glenn Hamonic, J Alex Pasternak, Heather L Wilson
Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be localized to the endosomes. However, continued research in this area shows that TLR localization may be altered across cell-types, and in response to stimulation, age or disease. Mucosal surfaces must remain tolerant to the commensal flora and thus intracellular or basal lateral localization of TLRs at mucosal surfaces may be necessary to prevent induction of an inflammatory response to commensal flora while still allowing the possibility for the receptors to prime an immune response when a pathogen has crossed the epithelial barrier...
January 12, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29330325/cutting-edge-plasmodium-falciparum-induces-trained-innate-immunity
#19
Jacob E Schrum, Juliet N Crabtree, Katherine R Dobbs, Michael C Kiritsy, George W Reed, Ricardo T Gazzinelli, Mihai G Netea, James W Kazura, Arlene E Dent, Katherine A Fitzgerald, Douglas T Golenbock
Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330321/osteopontin-promotes-protective-antigenic-tolerance-against-experimental-allergic-airway-disease
#20
Themis Alissafi, Evangelia Kourepini, Davina C M Simoes, Nikolaos Paschalidis, Maria Aggelakopoulou, Tim Sparwasser, Louis Boon, Hamida Hammad, Bart N Lambrecht, Vily Panoutsakopoulou
In the context of inflammation, osteopontin (Opn) is known to promote effector responses, facilitating a proinflammatory environment; however, its role during antigenic tolerance induction is unknown. Using a mouse model of asthma, we investigated the role of Opn during antigenic tolerance induction and its effects on associated regulatory cellular populations prior to disease initiation. Our experiments demonstrate that Opn drives protective antigenic tolerance by inducing accumulation of IFN-β-producing plasmacytoid dendritic cells, as well as regulatory T cells, in mediastinal lymph nodes...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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