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https://www.readbyqxmd.com/read/29334553/post-treatment-controllers-after-treatment-interruption-in-chronically-hiv-infected-patients
#1
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro
OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN: Patients were treated and monitored according to Italian guidelines...
January 13, 2018: AIDS
https://www.readbyqxmd.com/read/29328499/mait-cells-are-chronically-activated-in-patients-with-autoimmune-liver-disease-and-promote-pro-fibrogenic-hepatic-stellate-cell-activation
#2
Katrin Böttcher, Krista Rombouts, Francesca Saffioti, Davide Roccarina, Matteo Rosselli, Andrew Hall, TuVinh Luong, Emmanuel A Tsochatzis, Douglas Thorburn, Massimo Pinzani
Autoimmune liver diseases (AILD) are chronic liver pathologies characterised by fibrosis and cirrhosis due to immune-mediated liver damage. In this study, we addressed the question whether mucosal-associated invariant T (MAIT) cells, innate-like T cells, are functionally altered in patients with AILD and whether MAIT cells can promote liver fibrosis through activation of hepatic stellate cells. We analysed the phenotype and function of MAIT cells from AILD patients and healthy controls by multi-colour flow cytometry and investigated the interaction between human MAIT cells and primary human hepatic stellate cells (hHSCs)...
January 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29321824/high-frequency-of-cd34-cd38-low-immature-leukemia-cells-is-correlated-with-unfavorable-prognosis-in-acute-myeloid-leukemia
#3
Adriana Plesa, Charles Dumontet, Eve Mattei, Ines Tagoug, Sandrine Hayette, Pierre Sujobert, Isabelle Tigaud, Marie Pierre Pages, Youcef Chelghoum, Fiorenza Baracco, Helene Labussierre, Sophie Ducastelle, Etienne Paubelle, Franck Emmanuel Nicolini, Mohamed Elhamri, Lydia Campos, Claudiu Plesa, Stéphane Morisset, Gilles Salles, Yves Bertrand, Mauricette Michallet, Xavier Thomas
AIM: To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival. METHODS: Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France)...
December 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29320709/metabolic-reprogramming-via-targeting-cd38-nadase-augments-adoptive-t-cell-therapy
#4
Mario R Fernandez, John L Cleveland
One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4+ T cell functions and memory can be improved by targeting a CD38-NAD+-Sirt1-Foxo1 metabolic circuit.
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29316245/flow-cytometric-aberrancies-in-plasma-cell-myeloma-and-mgus-correlation-with-laboratory-parameters
#5
Sarika Gupta, Nitin J Karandikar, Timothy Ginader, Andrew M Bellizzi, Carol J Holman
BACKGROUND: Multiparametric flow cytometry (MFC) is a useful tool for diagnosis of plasma cell dyscrasias and assessment of minimal residual disease (MRD) in plasma cell myeloma (PCM). However, the immunophenotypic differences between the clonal plasma cells (PCs) of plasma cell myeloma (PCM) and those of monoclonal gammopathy of undetermined significance (MGUS) as well as the correlation of these flow cytometric markers with pertinent laboratory parameters have not been evaluated. METHODS: We retrospectively identified all newly diagnosed treatment-naive PCM and MGUS patients between 09/2014 and 06/2015 who underwent 10-color flow-cytometric evaluation: CD45, CD38, CD138, cKappa, cLambda, CD19, CD27, CD28, CD56, CD117...
January 6, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29316178/evaluation-of-cd229-as-a-new-alternative-plasma-cell-gating-marker-in-the-flow-cytometric-immunophenotyping-of-monoclonal-gammopathies
#6
Prashant R Tembhare, Sitaram Ghogale, Wilma Tauro, Yajamanam Badrinath, Nilesh Deshpande, Shweta Kedia, Keziah Cherian, Nikhil V Patkar, Gaurav Chatterjee, Sumeet Gujral, Papagudi G Subramanian
BACKGROUND: Current flow-cytometric plasma cell (PC) gating is based on CD138, CD38 and CD45 expression. CD138 is known for variable expression and loss during storage and processing. Introduction of anti-CD38 and anti-CD138 monoclonal-antibody therapies has limited the use of these markers during follow-up. Hence, additional reliable PC-gating markers are required. Recently, CD229 has been claimed as an alternative PC-gating marker. However, these studies are limited to a small cohort of samples...
January 9, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29312834/joint-damage-is-amplified-in-rheumatoid-arthritis-patients-with-positive-thyroid-autoantibodies
#7
Yu-Lan Chen, Jian-Zi Lin, Ying-Qian Mo, Jin-Jian Liang, Qian-Hua Li, Cheng-Jing Zhou, Xiu-Ning Wei, Jian-Da Ma, Ze-Hong Yang, Dong-Hui Zheng, Lie Dai
Background: Autoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse...
2018: PeerJ
https://www.readbyqxmd.com/read/29312564/azacitidine-combined-with-the-selective-flt3-kinase-inhibitor-crenolanib-disrupts-stromal-protection-and-inhibits-expansion-of-residual-leukemia-initiating-cells-in-flt3-itd-aml-with-concurrent-epigenetic-mutations
#8
Anne-Kathrin Garz, Saskia Wolf, Sonja Grath, Verena Gaidzik, Stefan Habringer, Binje Vick, Martina Rudelius, Christoph Ziegenhain, Sylvia Herold, Marie-Theresa Weickert, Martha Smets, Christian Peschel, Robert A J Oostendorp, Sebastian Bultmann, Irmela Jeremias, Christian Thiede, Konstanze Döhner, Ulrich Keller, Katharina S Götze
Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) eliminates FLT3-ITD LIC and whether efficacy of this combination depends on co-existing mutations...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306053/cd38-is-required-for-dendritic-organisation-in-visual-cortex-and-hippocampus
#9
Thom P Nelissen, Rosemary A Bamford, Shiro Tochitani, Kamuran Akkus, Aurimas Kudzinskas, Kenichiro Yokoi, Hiroshi Okamoto, Yasuhiko Yamamoto, J Peter H Burbach, Hideo Matsuzaki, Asami Oguro-Ando
Morphological screening of mouse brains with known behavioural deficits can give great insight into the relationship between brain regions and their behaviour. Oxytocin- and CD38-deficient mice have previously been shown to have behavioural phenotypes, such as restrictions in social memory, social interactions, and maternal behaviour. CD38 is reported as an autism spectrum disorder (ASD) candidate gene and these behavioural phenotypes may be linked to ASD. To address whether these behavioural phenotypes relate to brain pathology and neuronal morphology, here we investigate the morphological changes in the CD38-deficient mice brains, with focus on the pathology and neuronal morphology of the cortex and hippocampus, using Nissl staining, immunohistochemistry, and Golgi staining...
January 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#10
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29301755/copper-64-labeled-daratumumab-as-a-pet-ct-imaging-tracer-for-multiple-myeloma
#11
Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Paul Yazaki, Desiree Crow, Jihane Khalife, James F Sanchez, Joycelynne M Palmer, Susanta Hui, Nadia Carlesso, Jonathan Keats, Young Kim, Ralf Buettner, Guido Marcucci, Steven Rosen, John Shively, David Colcher, Amrita Krishnan, Flavia Pichiorri
As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often non-predictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a non-invasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluoro-deoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and non-malignant cells, results frequently lack sufficient specificity...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29298833/production-of-il-17-by-mait-cells-is-increased-in-multiple-sclerosis-and-is-associated-with-il-7-receptor-expression
#12
Anne Willing, Jan Jäger, Stefanie Reinhardt, Nina Kursawe, Manuel A Friese
Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#13
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296857/effects-of-daratumumab-on-natural-killer-cells-and-impact-on-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#14
Tineke Casneuf, Xu Steven Xu, Homer C Adams, Amy E Axel, Christopher Chiu, Imran Khan, Tahamtan Ahmadi, Xiaoyu Yan, Sagar Lonial, Torben Plesner, Henk M Lokhorst, Niels W C J van de Donk, Pamela L Clemens, A Kate Sasser
Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy and safety, were assessed...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296851/agonistic-targeting-of-tlr1-tlr2-induces-p38-mapk-dependent-apoptosis-and-nf%C3%AE%C2%BAb-dependent-differentiation-of-aml-cells
#15
Mia Eriksson, Pablo Peña-Martínez, Ramprasad Ramakrishnan, Marion Chapellier, Carl Högberg, Gabriella Glowacki, Christina Orsmark-Pietras, Talía Velasco-Hernández, Vladimir Lj Lazarević, Gunnar Juliusson, Jörg Cammenga, James C Mulloy, Johan Richter, Thoas Fioretos, Benjamin L Ebert, Marcus Järås
Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38- cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 in MLL-AF9-driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NFκB-dependent manner...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295624/nad-deficiency-is-a-common-central-pathological-factor-of-a-number-of-diseases-and-aging-mechanisms-and-therapeutic-implications
#16
Mingchao Zhang, Weihai Ying
Increasing evidence has indicated critical roles of NAD+ in various biological functions. NAD+ deficiency has been found in models of a number of diseases such as cerebral ischemia, myocardial ischemia and diabetes, and in models of aging. Application of NAD+ or other approaches that can restore NAD+ levels are highly protective in these models of diseases and aging. NAD+ produces its beneficial effects by targeting at multiple pathological pathways, including attenuating mitochondrial alterations, DNA damage and oxidative stress by modulating such enzymes as sirtuins, glyceraldehyde-3-phosphate dehydrogenase and AP endonuclease...
January 2, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29288900/increased-pd-1-cd154-tfh-cells-are-possibly-the-most-important-functional-subset-of-pd-1-t-follicular-helper-cells-in-adult-patients-with-minimal-change-disease
#17
Tao Li, Yunpeng Shi, Weixia Sun, Haifeng Wang, Quan Wang, Yanfang Jiang
T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)+ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1+, PD-1+CD154+, and PD-1+interleukin (IL)-21+ Tfh cells, and CD38+CD19+ and CD38+CD19+CD40+ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29287991/t-cell-phenotypes-in-women-with-chlamydia-trachomatis-infection-and-influence-of-treatment-on-phenotype-distributions
#18
Brian M O Ogendi, Rakesh K Bakshi, Kanupriya Gupta, Richa Kapil, LaDraka T Brown, Stephen J Jordan, Steffanie Sabbaj, Christen G Press, Jeannette Y Lee, William M Geisler
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women...
December 26, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29287090/immune-activation-despite-preserved-cd4-t-cells-in-perinatally-hiv-infected-children-and-adolescents
#19
Patricia Alvarez, Mussa Mwamzuka, Fatma Marshed, Adam Kravietz, Tiina Ilmet, Aabid Ahmed, William Borkowsky, Alka Khaitan
BACKGROUND: HIV disease progresses more rapidly in children than adults with mortality rates exceeding 50% by 2 years of age without antiretroviral therapy (ART) in sub-Saharan Africa. Recent World Health Organization (WHO) guidelines recommend universal treatment for all living persons with HIV, yet there is limited supporting evidence in pediatric populations. The objective of this study was to determine whether CD4 cell counts reflect immunological markers associated with disease progression in ART naïve perinatally-infected HIV+ children and adolescents and their response to ART...
2017: PloS One
https://www.readbyqxmd.com/read/29284680/cd36-defines-primitive-chronic-myeloid-leukemia-cells-less-responsive-to-imatinib-but-vulnerable-to-antibody-based-therapeutic-targeting
#20
Niklas Landberg, Sofia von Palffy, Maria Askmyr, Henrik Lilljebjörn, Carl Sandén, Marianne Rissler, Satu Mustjoki, Henrik Hjorth-Hansen, Johan Richter, Helena Ågerstam, Marcus Järås, Thoas Fioretos
Tyrosine kinase inhibitors are highly effective for treatment of chronic myeloid leukemia, but very few patients are cured. Major drawbacks with tyrosine kinase inhibitors are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase chronic myeloid leukemia cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells...
December 28, 2017: Haematologica
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