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https://www.readbyqxmd.com/read/28195263/kikuchi-fujimoto-disease-a-clinicopathologic-update
#1
F Pepe, S Disma, C Teodoro, P Pepe, G Magro
Kikuchi-Fujmoto disease (KFD), also known as "histiocytic necrotizing lymphadenitis", is a rare lymphadenitis of unknown origin, but with an excellent prognosis. It is more common in Asia, but isolated cases are also reported in America, Africa and Europe. The disease can have an acute or subacute course, usually develops in 1 to 3 weeks, with spontaneous resolution in 1-4 months. The main clinical sign is cervical lymphadenopathy, especially in the posterior cervical triangle with bulky and painful lymph nodes, usually affecting only one side; rare cases of generalized lymphadenopathy can be seen...
September 2016: Pathologica
https://www.readbyqxmd.com/read/28191591/plasmacytoid-dendritic-cell-proliferations-and-neoplasms-involving-the-bone-marrow-summary-of-the-workshop-cases-submitted-to-the-18th-meeting-of-the-european-association-for-haematopathology-eahp-organized-by-the-european-bone-marrow-working-group-basel-2016
#2
Alexandar Tzankov, Konnie Hebeda, Markus Kremer, Roos Leguit, Attilio Orazi, Jon van der Walt, Umberto Gianelli
Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF)...
February 12, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28164558/increased-number-of-mast-cells-in-atherosclerotic-lesions-correlates-with-the-presence-of-myeloid-but-not-plasmacytoid-dendritic-cells-as-well-as-pro-inflammatory-t-cells
#3
Ilonka Rohm, Sandra Sattler, Yevgeniya Atiskova, Daniel Kretzschmar, Rudin Pistulli, Marcus Franz, Christian Jung, Gita Mall, Thomas Kronert, Paul C Schulze, Atilla Yilmaz
BACKGROUND: Atherosclerosis is an inflammatory disease of the vessel wall promoted by different immune cells and inflammatory mediators. METHODS: In this study, 26 human plaques and 12 control vessels without atherosclerosis were immunohistochemically stained to analyze the emergence of mast cells dependent on plaque morphology and to correlate mast cell occurrence with the emergence of myeloid as well as plasmacytoid dendritic cells. Also, mast cell emergence was correlated with the number of pro-inflammatory T cells...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#4
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDS) arise from a small population of disease initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in stem and progenitor numbers are also seen in a stage specific manner in human MDS samples as well as in murine models of the disease...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28146632/antibody-targeted-cyclodextrin-based-nanoparticles-for-sirna-delivery-in-the-treatment-of-acute-myeloid-leukemia-physicochemical-characteristics-in-vitro-mechanistic-studies-and-ex-vivo-patient-derived-therapeutic-efficacy
#5
Jianfeng Guo, Eileen G Russell, Raphael Darcy, Thomas G Cotter, Sharon L McKenna, Mary R Cahill, Caitriona M O'Driscoll
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with high relapse rates. It is known that leukemia stem cells (LSCs), a very small subpopulation of the total number of leukemic cells, maintain the leukemia phenotype (∼80-90% of AML remain the same as at first diagnosis), display chemotherapy resistance, and contribute to disease regeneration. Therefore, targeting LSCs could control the relapse of AML. Small interfering RNA (siRNA), an effector of the RNA interference (RNAi) pathway, can selectively downregulate any gene implicated in the pathology of disease, presenting great potential for treatment of AML...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28096272/anti-leukemia-efficacy-and-mechanisms-of-action-of-sl-101-a-novel-anti-cd123-antibody-conjugate-in-acute-myeloid-leukemia
#6
Lina Han, Jeffrey L Jorgensen, Christopher Brooks, Ce Shi, Qi Zhang, Graciela M Nogueras González, Antonio Cavazos, Rongqing Pan, Hong Mu, Sa Wang, Jin Zhou, Gheath Alatrash, Stefan O Ciurea, Michael Rettig, John F DiPersio, Jorge E Cortes, Xuelin Huang, Hagop Kantarjian, Michael Andreeff, Farhad Ravandi-Kashani, Marina Konopleva
PURPOSE: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and anti-leukemia potency of a novel antibody-conjugate SL-101 in targeting CD123+ LSCs. Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD, and predicted shorter relapse-free survival in patients with poor-risk cytogenetics...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27917176/graft-immune-cell-composition-associates-with-clinical-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aml
#7
Ulla Impola, Antti Larjo, Urpu Salmenniemi, Mervi Putkonen, Maija Itälä-Remes, Jukka Partanen
Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#8
Jill M Sullivan, David A Rizzieri
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#9
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27881669/aerobic-exercise-in-humans-mobilizes-hscs-in-an-intensity-dependent-manner
#10
Jeff M Baker, Joshua P Nederveen, Gianni Parise
: Hematopoietic stem and progenitor cells are necessary to maintain, repair, and reconstitute the hematopoietic blood cell system. Mobilization of these cells from bone marrow to blood can be greatly increased under certain conditions, one such being exercise. The purpose of this study was to identify the importance of exercise intensity in hematopoietic mobilization, to better understand the mobilization kinetics postexercise, and to determine if exercise is capable of mobilizing several specific populations of hematopoietic cells that have clinical relevance in a transplant setting...
January 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27858122/increased-cd14-and-decreased-cd14-populations-of-monocytes-48%C3%A2-h-after-zolendronic-acid-infusion-in-breast-cancer-patients
#11
A Kyrgidis, M P Yavropoulou, R Lagoudaki, C Andreadis, K Antoniades, D Kouvelas
: It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes. INTRODUCTION: The aim of this study is to examine the effect of zolendronic acid administration in the peripheral blood white cell population, seeking a plausible pathophysiological link between bisphosphonates and osteonecrosis of the jaw...
November 17, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27837108/characterization-and-transcriptomic-analysis-of-porcine-blood-conventional-and-plasmacytoid-dendritic-cells-reveals-striking-species-specific-differences
#12
Gael Auray, Irene Keller, Sylvie Python, Markus Gerber, Remy Bruggmann, Nicolas Ruggli, Artur Summerfield
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135(+)CD14(-)CD172a(low)CADM1(+)wCD11R1(+) cells, cDC2 are CD135(+)CD14(-)CD172a(+)CADM1(+)CD115(+)wCD11R1(+)CD1(+) cells and pDCs are CD4(+)CD135(+)CD172a(+)CD123(+)CD303(+) cells...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27746164/type-of-monocyte-immunomagnetic-separation-affects-the-morphology-of-monocyte-derived-dendritic-cells-as-investigated-by-scanning-electron-microscopy
#13
M Kowalewicz-Kulbat, E Ograczyk, K Krawczyk, W Rudnicka, M Fol
Dendritic cells (DCs) are increasingly being used for multiple applications and are useful tools for many immunotherapeutic strategies. The understanding of the possible impact of the DCs-generation methods on the biological capacities of these cells is therefore essential. Although the immunomagnetic separation is regarded as a fast and accurate method yielding cells with the high purity and efficiency, still little is known about its impact on the properties of the generated DCs. The aim of this study was to compare the morphology of the monocyte derived dendritic cells (MoDCs), generated from monocytes selected with anti-CD14 mAbs (positive separation) and treated with anti-CD3, -CD7, -CD16, -CD19, -CD56, -CD123, glycophorin A (negative separation), using laser scanning microscopy...
October 13, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27733914/basophil-activation-test-in-oral-desensitization-to-cow-s-milk-allergy
#14
Salvatore Chirumbolo
The recent paper by Nucera et al., showed that the basophil activation test (BAT) in flow cytometry is able to monitor an acquired tolerance induced by a desensitization treatment in food allergy. The paper by Nucera et al. reported two standpoints in the CD63 response to food allergy and OAT and their large difference in CD63 response before and after suggests for the optimal performance of a CD123/HLADR/CD63 BAT in oral food allergy immunotherapy.
October 2016: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/27699260/a-cytotoxic-anti-il-3r%C3%AE-antibody-targets-key-cells-and-cytokines-implicated-in-systemic-lupus-erythematosus
#15
Shereen Oon, Huy Huynh, Tsin Yee Tai, Milica Ng, Katherine Monaghan, Mark Biondo, Gino Vairo, Eugene Maraskovsky, Andrew D Nash, Ian P Wicks, Nicholas J Wilson
To date, the major target of biologic therapeutics in systemic lupus erythematosus (SLE) has been the B cell, which produces pathogenic autoantibodies. Recently, targeting type I IFN, which is elaborated by plasmacytoid dendritic cells (pDCs) in response to endosomal TLR7 and TLR9 stimulation by SLE immune complexes, has shown promising results. pDCs express high levels of the IL-3Rα chain (CD123), suggesting an alternative potential targeting strategy. We have developed an anti-CD123 monoclonal antibody, CSL362, and show here that it affects key cell types and cytokines that contribute to SLE...
May 5, 2016: JCI Insight
https://www.readbyqxmd.com/read/27696572/distinct-interferon-gamma-and-interleukin-9-expression-in-cutaneous-and-oral-lichen-planus
#16
B Weber, C Schlapbach, M Stuck, H-U Simon, L Borradori, H Beltraminelli, D Simon
BACKGROUND: Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE: The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP...
October 1, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27687970/design-synthesis-and-evaluation-of-anti-cd123-antibody-drug-conjugates
#17
Bin Li, Weiyu Zhao, Xinfu Zhang, Junfeng Wang, Xiao Luo, Sharyn D Baker, Craig T Jordan, Yizhou Dong
Leukemia stem cells (LSCs) account for the development of drug resistance and increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug delivery to leukemia stem cells remains a major challenge in AML chemotherapy. Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of leukemia stem cells was reported to be a potential target in AML treatment. Here, we designed and developed an antibody drug conjugate (CD123-CPT) by integrating anti-CD123 antibody with a chemotherapeutic agent, Camptothecin (CPT), via a disulfide linker...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27672125/contrasting-expression-pattern-of-rna-sensing-receptors-tlr7-rig-i-and-mda5-in-interferon-positive-and-interferon-negative-patients-with-primary-sj%C3%A3-gren-s-syndrome
#18
Naomi I Maria, Eline C Steenwijk, Arne S IJpma, Cornelia G van Helden-Meeuwsen, Petra Vogelsang, Wouter Beumer, Zana Brkic, Paul L A van Daele, P Martin van Hagen, Peter J van der Spek, Hemmo A Drexhage, Marjan A Versnel
OBJECTIVE: The interferon (IFN) type I signature is present in over half of patients with primary Sjögren's syndrome (pSS) and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS. METHODS: Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature...
September 26, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27622386/early-treatment-with-reverse-transcriptase-inhibitors-significantly-suppresses-peak-plasma-ifn%C3%AE-in-vivo-during-acute-simian-immunodeficiency-virus-infection
#19
Jeffy George, Lynnsey Renn, Daniela Verthelyi, Mario Roederer, Ronald L Rabin, Joseph J Mattapallil
Innate interferons (IFN) are comprised of multiple Type I and III subtypes. The in vivo kinetics of subtype responses during human immunodeficiency virus (HIV) infection is not well defined. Using the acute simian immunodeficiency virus (SIV) infection model, we show that plasma IFNα levels peak at day 10 post-infection (pi) after which they rapidly declined. The mRNA expression of Type I and III IFN subtypes were significantly elevated in the lymph nodes (LN) at day 10 pi. Though the expression levels of all subtypes declined by day 14-31 pi, numerous subtypes remained elevated suggesting that ongoing viral replication in LN continues to drive induction of these subtypes...
September 9, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27571406/dual-cd19-and-cd123-targeting-prevents-antigen-loss-relapses-after-cd19-directed-immunotherapies
#20
Marco Ruella, David M Barrett, Saad S Kenderian, Olga Shestova, Ted J Hofmann, Jessica Perazzelli, Michael Klichinsky, Vania Aikawa, Farzana Nazimuddin, Miroslaw Kozlowski, John Scholler, Simon F Lacey, Jan J Melenhorst, Jennifer J D Morrissette, David A Christian, Christopher A Hunter, Michael Kalos, David L Porter, Carl H June, Stephan A Grupp, Saar Gill
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration...
October 3, 2016: Journal of Clinical Investigation
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