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https://www.readbyqxmd.com/read/29053773/less-is-more-neural-mechanisms-underlying-anomia-treatment-in-chronic-aphasic-patients
#1
Davide Nardo, Rachel Holland, Alexander P Leff, Cathy J Price, Jennifer T Crinion
Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted-for the first time-a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process...
September 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#2
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052600/ultrasensitive-automated-rna-in-situ-hybridization-for-kappa-and-lambda-light-chain-mrna-detects-b-cell-clonality-in-tissue-biopsies-with-performance-comparable-or-superior-to-flow-cytometry
#3
Ling Guo, Zhen Wang, Courtney M Anderson, Emerald Doolittle, Siobhan Kernag, Claudiu V Cotta, Sarah L Ondrejka, Xiao-Jun Ma, James R Cook
The assessment of B-cell clonality is a critical component of the evaluation of suspected lymphoproliferative disorders, but analysis from formalin-fixed, paraffin-embedded tissues can be challenging if fresh tissue is not available for flow cytometry. Immunohistochemical and conventional bright field in situ hybridization stains for kappa and lambda are effective for evaluation of plasma cells but are often insufficiently sensitive to detect the much lower abundance of light chains present in B-cells. We describe an ultrasensitive RNA in situ hybridization assay that has been adapted for use on an automated immunohistochemistry platform and compare results with flow cytometry in 203 consecutive tissues and 104 consecutive bone marrows...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29052038/proof-of-concept-coded-aperture-miniature-mass-spectrometer-using-a-cycloidal-sector-mass-analyzer-a-carbon-nanotube-cnt-field-emission-electron-ionization-source-and-an-array-detector
#4
Jason J Amsden, Philip J Herr, David M W Landry, William Kim, Raul Vyas, Charles B Parker, Matthew P Kirley, Adam D Keil, Kristin H Gilchrist, Erich J Radauscher, Stephen D Hall, James B Carlson, Nicholas Baldasaro, David Stokes, Shane T Di Dona, Zachary E Russell, Sonia Grego, Steven J Edwards, Roger P Sperline, M Bonner Denton, Brian R Stoner, Michael E Gehm, Jeffrey T Glass
Despite many potential applications, miniature mass spectrometers have had limited adoption in the field due to the tradeoff between throughput and resolution that limits their performance relative to laboratory instruments. Recently, a solution to this tradeoff has been demonstrated by using spatially coded apertures in magnetic sector mass spectrometers, enabling throughput and signal-to-background improvements of greater than an order of magnitude with no loss of resolution. This paper describes a proof of concept demonstration of a cycloidal coded aperture miniature mass spectrometer (C-CAMMS) demonstrating use of spatially coded apertures in a cycloidal sector mass analyzer for the first time...
October 19, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29050459/third-party-regulatory-t-cells-prevent-murine-acute-graft-versus-host-disease
#5
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Background/Aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention...
October 19, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29048671/adoptive-immunotherapy-combined-with-fp-treatment-for-head-and-neck-cancer-an-in%C3%A2-vitro-study
#6
Mayako Nishio-Nagai, Susumu Suzuki, Kazuhiro Yoshikawa, Ryuzo Ueda, Yoshiaki Kazaoka
FP treatment, which combines 5-fluorouracil (5-FU) and cisplatin (CDDP) chemotherapy, is widely used for treatment of advanced head and neck cancer (HNC). It has been suggested that these drugs cause immunomodulation in the cancer microenvironment, for example, downregulation of immunosuppressive cells such as regulatory T-cells (Tregs) and myeloid-derived suppressive cells (MDSCs), activating dendritic cells (DCs), and upregulation of tumor antigens and major histocompatibility complex (MHC) molecules in cancer cells leads to enhancement of cancer immunity, which is important in cancer treatment, as well as providing a direct killing effect...
October 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#7
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29048375/construction-of-a-bivalent-thrombin-binding-aptamer-and-its-antidote-with-improved-properties
#8
Quintin W Hughes, Bao T Le, Grace Gilmore, Ross I Baker, Rakesh N Veedu
Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson-Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often...
October 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29047021/the-influence-of-constructed-family-membership-on-hiv-risk-behaviors-among-gay-bisexual-and-other-men-who-have-sex-with-men-in-new-orleans
#9
Meagan C Zarwell, William T Robinson
Gay, bisexual, and other men who have sex with men (MSM) represent more new HIV infections than all other at-risk populations. Many young black MSM belong to constructed families (i.e., the house ball community, gay families, and pageant families) which are often organized in a family structure with members referred to as parents and children. Many constructed families are associated with a family surname which is informally adopted by members. In some cases, however, constructed families do not identify with a collective family name...
October 18, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/29046346/t-cell-derived-cd70-delivers-an-immune-checkpoint-function-in-inflammatory-t-cell-responses
#10
Rachel E O'Neill, Wei Du, Hemn Mohammadpour, Emad Alqassim, Jingxin Qiu, George Chen, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
The CD27-CD70 pathway is known to provide a costimulatory signal, with CD70 expressed on APCs and CD27 functions on T cells. Although CD70 is also expressed on activated T cells, it remains unclear how T cell-derived CD70 affects T cell function. Therefore, we have assessed the role of T cell-derived CD70 using adoptive-transfer models, including autoimmune inflammatory bowel disease and allogeneic graft-versus-host disease. Surprisingly, compared with wild-type T cells, CD70(-/-) T cells caused more severe inflammatory bowel disease and graft-versus-host disease and produced higher levels of inflammatory cytokines...
October 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29045907/reactive-neutrophil-responses-dependent-on-the-receptor-tyrosine-kinase-c-met-limit-cancer-immunotherapy
#11
Nicole Glodde, Tobias Bald, Debby van den Boorn-Konijnenberg, Kyohei Nakamura, Jake S O'Donnell, Sabrina Szczepanski, Maria Brandes, Sarah Eickhoff, Indrajit Das, Naveen Shridhar, Daniel Hinze, Meri Rogava, Tetje C van der Sluis, Janne J Ruotsalainen, Evelyn Gaffal, Jennifer Landsberg, Kerstin U Ludwig, Christoph Wilhelm, Monika Riek-Burchardt, Andreas J Müller, Christoffer Gebhardt, Richard A Scolyer, Georgina V Long, Viktor Janzen, Michele W L Teng, Wolfgang Kastenmüller, Massimiliano Mazzone, Mark J Smyth, Thomas Tüting, Michael Hölzel
Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045819/disruption-of-the-epidermal-barrier-induces-regulatory-t-cells-via-il-33-in-mice
#12
Anika Bruhs, Ehrhardt Proksch, Thomas Schwarz, Agatha Schwarz
Disturbance of the epidermal barrier by UV radiation (UVR) is associated with the release of antimicrobial peptides and inflammatory cytokines for the purpose of a danger response. On the other hand, UVR causes immunosuppression via regulatory T cells (Treg) which limit the inflammatory reaction. The concurrent induction of antimicrobial peptides and Treg by UVR may represent a counter-regulatory mechanism in response to barrier disruption, preventing microbial superinfection and sensitization to contact allergens, respectively, both of which cross impaired epidermis more easily...
October 15, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29045609/stakeholder-perspectives-on-the-optimizing-patient-transfers-impacting-medical-quality-and-improving-symptoms-transforming-institutional-care-optimistic-project
#13
Mary Ersek, Susan E Hickman, Anne C Thomas, Brittany Bernard, Kathleen T Unroe, Suzanne Meeks
Background and Objectives: The need to reduce burdensome and costly hospitalizations of frail nursing home residents is well documented. The Optimizing Patient Transfers, Impacting Medical Quality, and Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project achieved this reduction through a multicomponent collaborative care model. We conducted an implementation-focused project evaluation to describe stakeholders' perspectives on (a) the most and least effective components of the intervention; (b) barriers to implementation; and (c) program features that promoted its adoption...
October 17, 2017: Gerontologist
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#14
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29042721/clinical-and-radiographic-evaluation-of-citric-acid-based-nano-hydroxyapatite-composite-graft-in-the-regeneration-of-intrabony-defects-a-randomized-controlled-trial
#15
Chaurasia Priya Dayashankar, P C Deepika, Basavarajaiah Siddaramaiah
BACKGROUND: Conventional periodontal therapy with various bone grafts has limited scope and the results are not predictable. To improve their utility, the hybridization of bioceramics and biodegradable polymers has been widely adopted to reform the mechanical properties of bone grafts. One such biodegradable polymer is POC (Poly 1,8 octanediol). Secondly, citric acid is considered as the key material in bone mineralization, which is related to the overall stability, strength and fracture resistance of bone...
July 2017: Contemporary Clinical Dentistry
https://www.readbyqxmd.com/read/29042494/insights-from-the-genome-sequence-of-mycobacterium-lepraemurium-massive-gene-decay-and-reductive-evolution
#16
Andrej Benjak, Tanvi P Honap, Charlotte Avanzi, Enrique Becerril-Villanueva, Iris Estrada-García, Oscar Rojas-Espinosa, Anne C Stone, Stewart T Cole
Mycobacterium lepraemurium is the causative agent of murine leprosy, a chronic, granulomatous disease similar to human leprosy. Due to the similar clinical manifestations of human and murine leprosy and the difficulty of growing both bacilli axenically, Mycobacterium leprae and M. lepraemurium were once thought to be closely related, although it was later suggested that M. lepraemurium might be related to Mycobacterium avium In this study, the complete genome of M. lepraemurium was sequenced using a combination of PacBio and Illumina sequencing...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29042493/unraveling-the-self-assembly-of-the-pseudomonas-aeruginosa-xcpq-secretin-periplasmic-domain-provides-new-molecular-insights-into-type-ii-secretion-system-secreton-architecture-and-dynamics
#17
Badreddine Douzi, Nhung T T Trinh, Sandra Michel-Souzy, Aline Desmyter, Geneviève Ball, Pascale Barbier, Artemis Kosta, Eric Durand, Katrina T Forest, Christian Cambillau, Alain Roussel, Romé Voulhoux
The type II secretion system (T2SS) releases large folded exoproteins across the envelope of many Gram-negative pathogens. This secretion process therefore requires specific gating, interacting, and dynamics properties mainly operated by a bipartite outer membrane channel called secretin. We have a good understanding of the structure-function relationship of the pore-forming C-terminal domain of secretins. In contrast, the high flexibility of their periplasmic N-terminal domain has been an obstacle in obtaining the detailed structural information required to uncover its molecular function...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29042364/a-cd200r-cd28-fusion-protein-appropriates-an-inhibitory-signal-to-enhance-t-cell-function-and-therapy-of-murine-leukemia
#18
Shannon K Oda, Andrew W Daman, Nicolas M Garcia, Felecia Wagener, Thomas M Schmitt, Xiaoxia Tan, Aude G Chapuis, Philip D Greenberg
Acute myeloid leukemia (AML), the most common adult acute leukemia in the U.S., has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T cell responses. Expression of CD200 (OX2), a negative regulator of T cell function that binds CD200R, is commonly increased in leukemia and other malignancies, and is associated with poor prognosis in leukemia patients...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29039922/synthesis-and-crystal-structures-of-volatile-neptunium-iv-%C3%AE-diketonates
#19
Aaron T Johnson, T Gannon Parker, Sara M Dickens, Jana K Pfeiffer, Allen G Oliver, Donald Wall, Nathalie A Wall, Martha R Finck, Kevin P Carney
Production of certified reference materials in support of domestic nuclear forensics programs require volatile precursors for introduction into electromagnetic isotopic separation instruments. β-Diketone chelates of tetravalent actinides are known for their high volatility, but previously developed synthetic approaches require starting material (NpCl4) that is prohibitively difficult and hazardous to prepare. An alternative strategy was developed here that uses controlled potential electrolysis to reduce neptunium to the tetravalent state in submolar concentrations of hydrochloric acid...
October 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29039115/genome-editing-technologies-in-adoptive-t-cell-immunotherapy-for-cancer
#20
REVIEW
Nathan Singh, Junwei Shi, Carl H June, Marco Ruella
PURPOSE OF REVIEW: In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy. RECENT FINDINGS: Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies...
October 16, 2017: Current Hematologic Malignancy Reports
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