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Orange, jordan

Alexandre F Carisey, Emily M Mace, Mezida B Saeed, Daniel M Davis, Jordan S Orange
Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic cells through the formation of an immunological synapse. Actin remodeling at the lytic immunological synapse is a critical requirement for multiple facets of cytotoxic function. Activating receptor and integrin signaling leads to the regulated turnover and remodeling of actin, which is required for adhesion, sustained receptor signaling, and ultimately exocytosis. NK cells undergo lytic granule exocytosis in hypodense regions of a pervasive actin network...
January 30, 2018: Current Biology: CB
R Hirata, R R Pacheco, E Caceres, M N Janal, M F Romero, M Giannini, P G Coelho, F A Rueggeberg
OBJECTIVES: The aim of this study was to quantify the internal void volume formation in commercially available, resin composites inserted using conventional or sonic insertion methods, and analyzed using three-dimensional (3D) micro-computed tomography (μCT). METHODS AND MATERIALS: Four resin composites were evaluated: one conventional (Herculite, Ultra, Kerr Corporation, Orange, CA, USA), one flowable bulk fill (SureFil SDR Flow, Dentsply International, York, PA, USA), and two packable bulk fill (SonicFill, Kerr Corporation, and Tetric EvoCeram Bulk Fill, Ivoclar Vivadent Inc, Schaan, Liechtenstein)...
February 2, 2018: Operative Dentistry
Raquel Ruiz-García, Alexander Vargas-Hernandez, Ivan K Chinn, Laura S Angelo, Tram N Cao, Zeynep Coban-Akdemir, Shalini N Jhangiani, Qingchang Meng, Lisa R Forbes, Donna M Muzny, Luis M Allende, Mohammed S Ehlayel, Richard A Gibbs, James R Lupski, Gulbu Uzel, Jordan S Orange, Emily M Mace
BACKGROUND: Heterozygous gain-of-function mutations in PI3K110 lead to lymphadenopathy, lymphoid hyperplasia, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, and sinopulmonary infections. OBJECTIVE: The known role of NK cell function in the control of EBV and CMV prompted us to investigate the functional and phenotypic effect of PI3K110δ mutations on NK cell subsets and cytotoxic function. METHODS: Patient mutations were identified by whole exome or targeted sequencing...
January 9, 2018: Journal of Allergy and Clinical Immunology
Julia Zhu, Heather S Kirkham, Gretchen Ayer, Chi-Chang Chen, Rolin L Wade, Swapna U Karkare, Chester H Robson, Jordan S Orange
Objective: To compare clinical and economic outcomes of patients who received intravenous immunoglobulin (IVIG) therapies and were managed by a clinical management program vs the outcomes of matched controls using administrative claim data. Methods: This retrospective cohort study used the PharMetrics Plus™ claim database between September 1, 2011 and June 30, 2014. Patients in the intervention group were from a "high-touch" IVIG clinical management program administered by a home infusion specialty pharmacy...
2018: ClinicoEconomics and Outcomes Research: CEOR
Alexander Ngwube, I Celine Hanson, Jordan Orange, Nicholas L Rider, Filiz Seeborg, William Shearer, Lenora Noroski, Sarah Nicholas, Lisa Forbes, Kathryn Leung, Ghadir Sasa, Swati Naik, Meenakshi Hegde, Bilal Omer, Nabil Ahmed, Carl Allen, Stephen Gottschalk, Meng-Fen Wu, Hao Liu, Malcolm Brenner, Helen Heslop, Robert Krance, Caridad Martinez
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of 12 children who underwent allogeneic HSCT for WAS to report our experience...
March 2018: Biology of Blood and Marrow Transplantation
Alexander Vargas-Hernández, Emily M Mace, Ofer Zimmerman, Christa S Zerbe, Alexandra F Freeman, Sergio Rosenzweig, Jennifer W Leiding, Troy Torgerson, Matthew C Altman, Edith Schussler, Charlotte Cunningham-Rundles, Ivan K Chinn, Alexandre F Carisey, Imelda C Hanson, Nicholas L Rider, Steven M Holland, Jordan S Orange, Lisa R Forbes
BACKGROUND: Natural killer (NK) cells are critical innate effector cells whose development is dependent on the Janus kinase-signal transducer and activator of transcription (STAT) pathway. NK cell deficiency can result in severe or refractory viral infections. Patients with STAT1 gain-of-function (GOF) mutations have increased viral susceptibility. OBJECTIVE: We sought to investigate NK cell function in patients with STAT1 GOF mutations. METHODS: NK cell phenotype and function were determined in 16 patients with STAT1 GOF mutations...
October 27, 2017: Journal of Allergy and Clinical Immunology
Emanuela Marcenaro, Luigi D Notarangelo, Jordan S Orange, Eric Vivier
No abstract text is available yet for this article.
2017: Frontiers in Immunology
Maksim Mamonkin, Malini Mukherjee, Madhuwanti Srinivasan, Sandhya Sharma, Diogo Gomes-Silva, Feiyan Mo, Giedre Krenciute, Jordan S Orange, Malcolm K Brenner
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant T cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR T cells rapidly differentiated into short-lived effector cells. In contrast, 4-1BB costimulation is known to promote development of the central memory subpopulation. Here, we found BB.z CD5 CAR T cells had impaired growth compared with 28...
January 2018: Cancer Immunology Research
Christopher D Nishimura, Daniel A Brenner, Malini Mukherjee, Rachel A Hirsch, Leah Ott, Meng-Fen Wu, Hao Liu, Olga Dakhova, Jordan S Orange, Malcolm K Brenner, Charles Y Lin, Caroline Arber
Adoptively transferred T cell receptor (TCR)-engineered T-cells depend on host-derived co-stimulation and cytokine signals for their full and sustained activation. However, in cancer patients both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in one transgene by expressing the non-lymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T-cells. C-MPL signaling activates pathways shared with conventional co-stimulatory and cytokine receptor signaling...
October 27, 2017: Blood
Dipika R Patel, Julia E M Upton, Julie Wang, Laurie Harada, Danielle Guffey, Charles G Minard, Jordan Orange, Carla M Davis
No abstract text is available yet for this article.
October 17, 2017: Journal of Allergy and Clinical Immunology in Practice
Kevin Bielamowicz, Kristen Fousek, Tiara T Byrd, Hebatalla Samaha, Malini Mukherjee, Nikita Aware, Meng-Fen Wu, Jordan S Orange, Pavel Sumazin, Tsz-Kwong Man, Sujith K Joseph, Meenakshi Hegde, Nabil Ahmed
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric Antigen Receptor (CAR) T-cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of two glioma antigens offsets antigen escape and enhances T-cell effector functions, the inter-patient variability in surface antigen expression between patients hinders the clinical impact of targeting two antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application...
September 16, 2017: Neuro-oncology
Diogo Gomes-Silva, Malini Mukherjee, Madhuwanti Srinivasan, Giedre Krenciute, Olga Dakhova, Yueting Zheng, Joaquim M S Cabral, Cliona M Rooney, Jordan S Orange, Malcolm K Brenner, Maksim Mamonkin
Antigen-independent tonic signaling by chimeric antigen receptors (CARs) can increase differentiation and exhaustion of T cells, limiting their potency. Incorporating 4-1BB costimulation in CARs may enable T cells to resist this functional exhaustion; however, the potential ramifications of tonic 4-1BB signaling in CAR T cells remain unclear. Here, we found that tonic CAR-derived 4-1BB signaling can produce toxicity in T cells via continuous TRAF2-dependent activation of the nuclear factor κB (NF-κB) pathway and augmented FAS-dependent cell death...
October 3, 2017: Cell Reports
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
Chu Hsiao, Christopher Jordan Clukay
No abstract text is available yet for this article.
September 1, 2017: JAMA Dermatology
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...
October 2017: Immunologic Research
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...
December 2017: Lasers in Medical Science
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
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
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...
October 2, 2017: Journal of Cell Biology
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
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