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https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#1
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28903145/orangeness-peeling-back-the-myths-behind-carotenemia
#2
Chu Hsiao, Christopher Jordan Clukay
No abstract text is available yet for this article.
September 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28822075/recycling-endosomes-in-human-cytotoxic-t-lymphocytes-constitute-an-auxiliary-intracellular-trafficking-pathway-for-newly-synthesized-perforin
#3
Kelsey Lesteberg, Jordan Orange, George Makedonas
Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin...
August 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28812169/bond-strength-of-etch-and-rinse-and-self-etch-adhesive-systems-to-enamel-and-dentin-irradiated-with-a-novel-co2-9-3%C3%A2-%C3%AE-m-short-pulsed-laser-for-dental-restorative-procedures
#4
Peter Rechmann, N Bartolome, R Kinsel, R Vaderhobli, B M T Rechmann
The objective of this study was to evaluate the influence of CO2 9.3 μm short-pulsed laser irradiation on the shear bond strength of composite resin to enamel and dentin. Two hundred enamel and 210 dentin samples were irradiated with a 9.3 µm carbon dioxide laser (Solea, Convergent Dental, Inc., Natick, MA) with energies which either enhanced caries resistance or were effective for ablation. OptiBond Solo Plus [OptiBondTE] (Kerr Corporation, Orange, CA) and Peak Universal Bond light-cured adhesive [PeakTE] (Ultradent Products, South Jordan, UT) were used...
August 15, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28770187/t-cell-lymphopenia-detected-by-newborn-screening-in-two-siblings-with-an-xq13-1-duplication
#5
Xavier Rios, Ivan K Chinn, Jordan S Orange, Celine I Hanson, Nicholas L Rider
Newborn screening for severe combined immunodeficiency has proven successful in identifying infants with T-cell deficiencies before they become severely ill. Additionally, the newborn screen can detect subtle early phenotypes that may become severe later in life. We present the case of siblings with features suggestive of T-cell lymphopenia identified as having low T-cell receptor excision circles counts by newborn screening. Expanded immune testing showed robust lymphocyte mitogen and antigen responses with normal vaccine responses and immunoglobulin levels for both boys over time...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28767726/high-resolution-phenotyping-identifies-nk-cell-subsets-that-distinguish-healthy-children-from-adults
#6
Sanjana Mahapatra, Emily M Mace, Charles G Minard, Lisa R Forbes, Alexander Vargas-Hernandez, Teresa K Duryea, George Makedonas, Pinaki P Banerjee, William T Shearer, Jordan S Orange
Natural killer (NK) cells are critical in immune defense against infected, stressed or transformed cells. Their function is regulated by the heterogeneous expression of a wide array of surface receptors that shape its phenotypic diversity. Although NK cells develop in the bone marrow and secondary lymphoid tissues, substantive differentiation is apparent in the peripheral blood including known age-related variation. In order to gain greater insight into phenotypic and functional variation within peripheral blood NK cells across age groups, we used multi-parametric, polyfunctional flow cytometry to interrogate the NK cell variability in 20 healthy adults and 15 5-10, 11-15 and 16-20 year-old children...
2017: PloS One
https://www.readbyqxmd.com/read/28765364/filoquant-reveals-increased-filopodia-density-during-breast-cancer-progression
#7
Guillaume Jacquemet, Ilkka Paatero, Alexandre F Carisey, Artur Padzik, Jordan S Orange, Hellyeh Hamidi, Johanna Ivaska
Defective filopodia formation is linked to pathologies such as cancer, wherein actively protruding filopodia, at the invasive front, accompany cancer cell dissemination. Despite wide biological significance, delineating filopodia function in complex systems remains challenging and is particularly hindered by lack of compatible methods to quantify filopodia properties. Here, we present FiloQuant, a freely available ImageJ plugin, to detect filopodia-like protrusions in both fixed- and live-cell microscopy data...
August 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28680749/tumor-priming-converts-nk-cells-to-memory-like-nk-cells
#8
Marina Pal, Lisa Schwab, Anastasiya Yermakova, Emily M Mace, Rainer Claus, Ann-Christin Krahl, Jeanette Woiterski, Udo F Hartwig, Jordan S Orange, Rupert Handgretinger, Maya C André
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679735/hematopoietic-stem-cell-transplantation-in-29-patients-hemizygous-for-hypomorphic-ikbkg-nemo-mutations
#9
Charline Miot, Kohsuke Imai, Chihaya Imai, Anthony J Mancini, Zeynep Yesim Kucuk, Tokomki Kawai, Ryuta Nishikomori, Etsuro Ito, Isabelle Pellier, Sophie Dupuis Girod, Jeremie Rosain, Shinya Sasaki, Shanmuganathan Chandrakasan, Jana Pachlopnik Schmid, Tsubasa Okano, Estelle Colin, Alberto Olaya-Vargas, Marco Yamazaki-Nakashimada, Waseem Qasim, Sara Espinosa Padilla, Andrea Jones, Alfons Krol, Nyree Cole, Stephen Jolles, Jack Bleesing, Thomas Vraetz, Andrew R Gennery, Mario Abinun, Tayfun Güngör, Beatriz Costa-Carvalho, Antonio Condino-Neto, Paul Veys, Steven M Holland, Gulbu Uzel, Despina Moshous, Benedicte Neven, Stéphane Blanche, Stephan Ehl, Rainer Döffinger, Smita Y Patel, Anne Puel, Jacinta Bustamante, Erwin W Gelfand, Jean-Laurent Casanova, Jordan S Orange, Capucine Picard
X-linked recessive ectodermal dysplasia (EDA) with immunodeficiency (XR-EDA-ID) is a rare primary immunodeficiency (PID) caused by hypomorphic mutations of the IKBKG gene encoding the NEMO protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and non-hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests that it has been reserved for only the most severe cases...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28663103/quantitative-imaging-approaches-to-study-the-car-immunological-synapse
#10
REVIEW
Malini Mukherjee, Emily M Mace, Alexandre F Carisey, Nabil Ahmed, Jordan S Orange
The lytic immunological synapse (IS) is a discrete structural entity formed after the ligation of specific activating receptors that leads to the destruction of a cancerous cell. The formation of an effector cell IS in cytotoxic T lymphocytes or natural killer cells is a hierarchical and stepwise rearrangement of structural and signaling components and targeted release of the contents of lytic granules. While recent advances in the generation and testing of cytotoxic lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated their efficacy in the targeted lysis of tumor targets, the contribution and dynamics of IS components have not yet been extensively investigated in the context of engineered CAR cells...
August 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28626510/multispecialty-rating-of-evidence-based-conditions-for-intravenous-immunoglobulin-therapy-using-a-3-axis-prioritization-algorithm
#11
Jordan S Orange, Matt Johnson, Barb Lennert, Katarzyna Shields, Michael Eaddy
BACKGROUND: A 3-axis prioritization algorithm was proposed and was evaluated in a US multispecialist pilot study to obtain uniform consensus regarding effective practices for the use of intravenous immunoglobulin (IVIG) therapy. OBJECTIVE: The primary objective was to use consensus-building methodologies to rate disease states for IVIG utilization while considering disease severity and the efficacy of alternative therapeutic options to IVIG from the perspective of US multispecialists...
May 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28603521/novel-combined-immune-deficiency-and-radiation-sensitivity-blended-phenotype-in-an-adult-with-biallelic-variations-in-zap70-and-rnf168
#12
Ivan K Chinn, Robert P Sanders, Asbjørg Stray-Pedersen, Zeynep H Coban-Akdemir, Vy Hong-Diep Kim, Harjit Dadi, Chaim M Roifman, Troy Quigg, James R Lupski, Jordan S Orange, I Celine Hanson
With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these "mendelizing" disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588580/specific-antibody-deficiency-controversies-in-diagnosis-and-management
#13
REVIEW
Elena Perez, Francisco A Bonilla, Jordan S Orange, Mark Ballow
Specific antibody deficiency (SAD) is a primary immunodeficiency disease characterized by normal immunoglobulins (Igs), IgA, IgM, total IgG, and IgG subclass levels, but with recurrent infection and diminished antibody responses to polysaccharide antigens following vaccination. There is a lack of consensus regarding the diagnosis and treatment of SAD, and its clinical significance is not well understood. Here, we discuss current evidence and challenges regarding the diagnosis and treatment of SAD. SAD is normally diagnosed by determining protective titers in response to the 23-valent pneumococcal polysaccharide vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28583665/overview-nk-cell-based-immunotherapies-toward-into-clinical-trials
#14
EDITORIAL
Mark A Exley, Jordan S Orange
No abstract text is available yet for this article.
April 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28555177/changes-in-frequency-and-activation-status-of-major-cd4-t-cell-subsets-after-initiation-of-immunosuppressive-therapy-in-a-patient-with-new-diagnosis-childhood-onset-systemic-lupus-erythematosus
#15
Saimun Singla, Scott E Wenderfer, Eyal Muscal, Anna Carmela P Sagcal-Gironella, Jordan S Orange, George Makedonas
BACKGROUND: Several studies suggest that defects of regulatory T-cells (Tregs) and impaired cellular immunity are secondary to an imbalance between auto-aggressive T-cells and Tregs in lupus patients. Discrepancies in Tregs and effector T-cells (Teff) in active lupus patients are shown to be restored in patients upon receiving immunosuppressive therapy. Therefore, our main aim was to observe frequencies of these CD4(+) T-cell subsets and Tregs/Teff ratio in a new diagnosis of childhood-onset systemic lupus erythematous (cSLE) before and after initiation of therapy...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28536745/health-related-quality-of-life-in-adult-patients-with-common-variable-immunodeficiency-disorders-and-impact-of-treatment
#16
Nicholas L Rider, Carleigh Kutac, Joud Hajjar, Chris Scalchunes, Filiz O Seeborg, Marcia Boyle, Jordan S Orange
PURPOSE: Common variable immunodeficiency disorder (CVID) is a primary immunodeficiency disease (PIDD) often associated with severe and chronic infections. Patients commonly receive immunoglobulin (Ig) treatment to reduce the cycle of recurrent infection and improve physical functioning. However, how Ig treatment in CVID affects quality of life (QOL) has not been thoroughly evaluated. The purpose of a recent Immune Deficiency Foundation (IDF) mail survey was to assess the factors that are associated with QOL in patients with CVID receiving Ig treatment...
July 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28455356/the-coordinating-role-of-iqgap1-in-the-regulation-of-local-endosome-specific-actin-networks
#17
Edward B Samson, David S Tsao, Jan Zimak, R Tyler McLaughlin, Nicholaus J Trenton, Emily M Mace, Jordan S Orange, Volker Schweikhard, Michael R Diehl
IQGAP1 is a large, multi-domain scaffold that helps orchestrate cell signaling and cytoskeletal mechanics by controlling interactions among a spectrum of receptors, signaling intermediates, and cytoskeletal proteins. While this coordination is known to impact cell morphology, motility, cell adhesion, and vesicular traffic, among other functions, the spatiotemporal properties and regulatory mechanisms of IQGAP1 have not been fully resolved. Herein, we describe a series of super-resolution and live-cell imaging analyses that identified a role for IQGAP1 in the regulation of an actin cytoskeletal shell surrounding a novel membranous compartment that localizes selectively to the basal cortex of polarized epithelial cells (MCF-10A)...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28438538/linking-newborn-severe-combined-immunodeficiency-screening-with-targeted-exome-sequencing-a-case-report
#18
Dipika R Patel, Hui Yu, Lee-Jun C Wong, James R Lupski, Filiz O Seeborg, Nicholas L Rider, Caridad A Martinez, Jordan S Orange, Celine Hanson
No abstract text is available yet for this article.
September 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28327206/lessons-learned-from-additional-research-analyses-of-unsolved-clinical-exome-cases
#19
Mohammad K Eldomery, Zeynep Coban-Akdemir, Tamar Harel, Jill A Rosenfeld, Tomasz Gambin, Asbjørg Stray-Pedersen, Sébastien Küry, Sandra Mercier, Davor Lessel, Jonas Denecke, Wojciech Wiszniewski, Samantha Penney, Pengfei Liu, Weimin Bi, Seema R Lalani, Christian P Schaaf, Michael F Wangler, Carlos A Bacino, Richard Alan Lewis, Lorraine Potocki, Brett H Graham, John W Belmont, Fernando Scaglia, Jordan S Orange, Shalini N Jhangiani, Theodore Chiang, Harsha Doddapaneni, Jianhong Hu, Donna M Muzny, Fan Xia, Arthur L Beaudet, Eric Boerwinkle, Christine M Eng, Sharon E Plon, V Reid Sutton, Richard A Gibbs, Jennifer E Posey, Yaping Yang, James R Lupski
BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease...
March 21, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28255722/measurement-of-lytic-granule-convergence-after-formation-of-an-nk-cell-immunological-synapse
#20
Hsiang-Ting Hsu, Alexandre F Carisey, Jordan S Orange
Natural killer (NK) cells contain specialized lysosome-related organelles termed lytic granules allowing them to mediate cytotoxicity against tumorigenic or virally infected target cells. NK cells polarize their lytic granules toward a target cell via the microtubule-organizing center (MTOC). Prior to that, however, lytic granules converge to the MTOC along microtubules utilizing minus-end-directed microtubule motors. Herein we describe how to visualize and quantify lytic granule convergence using confocal microscopy to gain quantitative insight into NK cell cytotoxicity and its regulation...
2017: Methods in Molecular Biology
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