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Cell exhaustion

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https://www.readbyqxmd.com/read/29236302/recovery-of-hepatitis-c-specific-t-cell-responses-after-rituximab-therapy-in-hepatitis-c-mixed-cryoglobulinemic-vasculitis
#1
Poonam Mathur, Benjamin Emmanuel, Michael Sneller, Xiaozhen Zhang, Bhawna Poonia, Shyamasundaran Kottilil
BACKGROUND & AIMS: Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function. METHODS: Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375mg/m2 ) and variables were measured 6 months after therapy...
December 13, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29234685/local-and-systemic-cd4-t-cell-exhaustion-reverses-with-clinical-resolution-of-pulmonary-sarcoidosis
#2
Charlene Hawkins, Guzel Shaginurova, D Auriel Shelton, Jose D Herazo-Maya, Kyra A Oswald-Richter, Joseph E Rotsinger, Anjuli Young, Lindsay J Celada, Naftali Kaminski, Carla Sevin, Wonder P Drake
Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29234103/an-exhaustive-search-algorithm-to-aid-nmr-based-structure-determination-of-rotationally-symmetric-transmembrane-oligomers
#3
Jing Yang, Alessandro Piai, Hong-Bin Shen, James J Chou
Nuclear magnetic resonance (NMR) has been an important source of structural restraints for solving structures of oligomeric transmembrane domains (TMDs) of cell surface receptors and viral membrane proteins. In NMR studies, oligomers are assembled using inter-protomer distance restraints. But, for oligomers that are higher than dimer, these distance restraints all have two-fold directional ambiguity, and resolving such ambiguity often requires time-consuming trial-and-error calculations using restrained molecular dynamics (MD) with simulated annealing (SA)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#4
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29232209/recent-progress-in-understanding-hiv-reservoirs
#5
Hsiao-Hsuan Kuo, Mathias Lichterfeld
PURPOSE OF REVIEW: Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. RECENT FINDINGS: Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs...
December 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29231614/-effects-of-preventative-moxibustion-on-ampk-and-mtor-in-myocardial-tissue-in-rats-with-exhaustive-exercise
#6
Haoran Zhang, Hongru Zhang, Shengfeng Lu, Hua Bai, Yihuang Gu
OBJECTIVE: To observe the effects of preventative moxibustion on adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in myocardial tissue in rats with exhaustive exercise, and to explore the action mechanism of preventative moxibustion for myocardial injury by exhaustive exercise. METHODS: Eighteen SD male rats were randomly divided into a blank group, an exhaustive exercise group and a moxibustion group, 6 rats in each one...
May 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29227121/-what%C3%A2-s%C3%A2-new-in-ewing-like-sarcoma-family-soft-tissue-and-bone-sarcomas-with-cic-bcor-rearrangement-review-of-the-literature-and-first-personal-experience
#7
Zdeněk Kinkor, Petr Grossmann, Magdaléna Dubová, David Bludovský, Andrea Černá, Lenka Krsková, Petr Lhoták
The literature is reviewed regarding of a rare molecularly defined group of sarcomas with rearrangement of both CIC and BCOR genes, which were originally placed into the EWSR1wt Ewing-like category. Personal experience with three cases demonstrating difficulties of this issue is added. Both groups of lesions differ not only by age and topography, but also vary in both the prognostic and the predictive parameters. CIC-rearranged tumors are very aggressive and almost never occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly bone tumors in young males behaving even better than classical Ewing sarcoma...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29225037/understanding-and-sensitizing-density-dependent-persistence-to-quinolone-antibiotics
#8
Arnaud Gutierrez, Saloni Jain, Prerna Bhargava, Meagan Hamblin, Michael A Lobritz, James J Collins
Physiologic and environmental factors can modulate antibiotic activity and thus pose a significant challenge to antibiotic treatment. The quinolone class of antibiotics, which targets bacterial topoisomerases, fails to kill bacteria that have grown to high density; however, the mechanistic basis for this persistence is unclear. Here, we show that exhaustion of the metabolic inputs that couple carbon catabolism to oxidative phosphorylation is a primary cause of growth phase-dependent persistence to quinolone antibiotics...
December 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29224832/the-pathogenesis-of-pulmonary-sarcoidosis-and-implications-for-treatment
#9
REVIEW
Karen C Patterson, Edward S Chen
Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a heterogeneous group of patients with a wide range of clinical features and associated outcomes. The distinction between isolated thoracic lymphadenopathy and pulmonary involvement matters. Morbidity is often higher, and long-term outcomes are worse for the latter. While inflammatory infiltrates in pulmonary sarcoidosis may resolve, persistent disease activity is common and can result in lung fibrosis. Given the distinct clinical features and natural history of pulmonary sarcoidosis, its pathogenesis may differ in important ways from other sarcoidosis manifestations...
December 7, 2017: Chest
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#10
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
PURPOSE: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing co-inhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. EXPERIMENTAL DESIGN: Surface expression of 9 co-inhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#11
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29215751/proteomic-response-of-the-rat-liver-in-differential-swimming-modes
#12
Liang Chen, Yanhua Yang, Yiting Wang, Lipeng Qiu, Hengchuan Xia, Aiai Wang, Hailong Liu, Hongfei Shi, Keping Chen
Moderate exercise helps improve competition results, providing a balanced muscle tone and biochemical activity, whereas excessive training disrupts the balance between training and recovery, causes harm to the organism, and leads to overtraining syndrome (OTS). To explore the mechanisms of different protein expressions during training and acquisition of immunity, we used proteomic analyses to investigate the differences of liver-protein expressions between two swimming modes. Sprague-Dawley rats were randomly divided into control (CT), fatigue training (FT), and exhaustive training (ET) groups, and liver tissues from each group were subjected to two-dimensional electrophoresis (2DE)...
December 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29215066/pharmacological-inhibition-of-rev-erb-stimulates-differentiation-inhibits-turnover-and-reduces-fibrosis-in-dystrophic-muscle
#13
Ryan D Welch, Cyrielle Billon, Aurore-Cecile Valfort, Thomas P Burris, Colin A Flaveny
Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214921/heteropterys-tomentosa-a-juss-toxicological-and-adaptogenic-effects-in-experimental-models
#14
Géssica Alves Fraga, Sikiru Olaitan Balogun, Emilly Della Pascqua, Ruberlei Godinho de Oliveira, Guilherme Botelho, Eduarda Pavan, Thiago da Rosa Lima, Eudes Thiago Pereira Avila, Clarissa de Medeiros Amorim Krueger, Valdir Cechinel Filho, Amílcar Sabino Damazo, Domingos Tabajara de Oliveira Martins, Fabrício Azevedo Voltarelli
BACKGROUND: The constant pursuit of improved athletic performance characterizes high-performance sport and the use of medicinal plants as dietary supplements is becoming widespread among athletes to enhance long-term endurance performance. AIM: The present study evaluated the toxicity of Heteropterys tomentosa (HEHt) and its acute adaptogenic effects. METHODS: The in vitro safety profile was evaluated on CHO-k1 cells using the alamar Blue assay, at concentrations ranging from 3...
December 2017: Nutrition and Health
https://www.readbyqxmd.com/read/29214640/management-of-head-and-neck-primary-unknown-squamous-cell-carcinoma-using-combined-positron-emission-tomography-computed-tomography-and-transoral-laser-microsurgery
#15
Victoria Kuta, Blair Williams, Matthew Rigby, Robert Hart, Jonathan Trites, Colin MacKay, S Mark Taylor
OBJECTIVES/HYPOTHESIS: The unknown primary of the neck is commonly encountered by the head and neck surgeon. Despite the exhaustive diagnostic tools employed in traditional detection protocols, many unknown primaries are not found, and the patient is subjected to wide-field radiation and chemotherapy during treatment. Localizing the primary tumor has demonstrated therapeutic benefits, improved quality of life, and overall survival. The authors' objective was to determine the efficacy of a new management protocol for unknown primaries of the head and neck...
December 7, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29213079/human-cd26high-t-cells-elicit-tumor-immunity-against-multiple-malignancies-via-enhanced-migration-and-persistence
#16
Stefanie R Bailey, Michelle H Nelson, Kinga Majchrzak, Jacob S Bowers, Megan M Wyatt, Aubrey S Smith, Lillian R Neal, Keisuke Shirai, Carmine Carpenito, Carl H June, Michael J Zilliox, Chrystal M Paulos
CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29211494/exhaustion-of-airway-basal-progenitor-cells-in-early-and-established-copd
#17
Moumita Ghosh, York E Miller, Ichiro Nakachi, Jennifer B Kwon, Anna E Barón, Alexandra E Brantley, Daniel T Merrick, Wilbur A Franklin, Robert L Keith, R William Vandivier
RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, pre-diagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience, because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired...
December 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29209275/lipid-uptake-metabolism-and-transport-in-the-larval-zebrafish
#18
REVIEW
Vanessa H Quinlivan, Steven A Farber
The developing zebrafish is a well-established model system for studies of energy metabolism, and is amenable to genetic, physiological, and biochemical approaches. For the first 5 days of life, nutrients are absorbed from its endogenous maternally deposited yolk. At 5 days post-fertilization, the yolk is exhausted and the larva has a functional digestive system including intestine, liver, gallbladder, pancreas, and intestinal microbiota. The transparency of the larval zebrafish, and the genetic and physiological similarity of its digestive system to that of mammals make it a promising system in which to address questions of energy homeostasis relevant to human health...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29198314/t-cell-resistance-to-activation-by-dendritic-cells-requires-long-term-culture-in-simulated-microgravity
#19
Jillian H Bradley, Rachel Stein, Brad Randolph, Emily Molina, Jennifer P Arnold, Randal K Gregg
Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines...
November 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29197679/recipient-t-cell-exhaustion-and-successful-adoptive-transfer-of-haploidentical-natural-killer-cells
#20
Robin L Williams, Sarah Cooley, Veronika Bachanova, Bruce R Blazar, Daniel J Weisdorf, Jeffrey S Miller, Michael R Verneris
NK cells mediate surveillance for malignancy. In some chemotherapy refractory myeloid leukemia patients, adoptive transfer of NK cells from haploidentical donors can induce remission. We have previously shown that remission induction is linked to NK persistence at D+14, but the factors influencing NK cell persistence are unknown. To address this question, patient samples from a phase I trial of NCI IL-15 in whom either did or did not show NK cell expansion were compared to healthy donor controls. Prior to lymphodepleting chemotherapy, high absolute CD3+ count was predictive of patients who failed to expand their haplo-NK cell graft...
November 29, 2017: Biology of Blood and Marrow Transplantation
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