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https://www.readbyqxmd.com/read/28978170/imatinib-in-systemic-mastocytosis-a-phase-iv-clinical-trial-in-patients-lacking-exon-17-kit-mutations-and-review-of-the-literature
#1
Iván Alvarez-Twose, Almudena Matito, José Mário Morgado, Laura Sánchez-Muñoz, María Jara-Acevedo, Andrés García-Montero, Andrea Mayado, Carolina Caldas, Cristina Teodósio, Javier Ignacio Muñoz-González, Manuela Mollejo, Luis Escribano, Alberto Orfao
Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. We evaluated the efficacy and safety of imatinib therapy in 10 adult SM patients lacking exon 17 KIT mutations, 9 of which fulfilled criteria for well-differentiated SM (WDSM). The World Health Organization 2008 disease categories among WDSM patients were mast cell (MC) leukemia (n = 3), indolent SM (n = 3) and cutaneous mastocytosis (n = 3); the remainder case had SM associated with a clonal haematological non-MC disease...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965920/selection-and-validation-of-antibody-clones-against-igg-and-iga-subclasses-in-switched-memory-b-cells-and-plasma-cells
#2
Elena Blanco, Martin Perez-Andres, Luzalba Sanoja-Flores, Marjolein Wentink, Ondrej Pelak, Marta Martín-Ayuso, Georgiana Grigore, Juan Torres-Cañizales, Eduardo López-Granados, Tomas Kalina, Mirjam Van der Burg, Sonia Arriba-Méndez, Santiago Santa Cruz, Noemí Puig, Jacques J M van Dongen, Alberto Orfao
The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, but except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry...
September 28, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28844608/risk-factors-for-the-occurrence-of-epistaxis-prospective-study
#3
Filipa Camacho Côrte, Tiago Orfao, Cláudia Camila Dias, Carla Pinto Moura, Margarida Santos
OBJECTIVE: Analyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors. METHODS: Prospective analysis of 283 consecutive adults, admitted to the otolaryngology emergency department of a tertiary referral centre between 25 January and 25 February 2014. Comparison of gender, age, co-morbidities, usual medication, history of epistaxis or nasal trauma, presence of septal deviation and blood pressure value on admission, between the elements that were admitted to the emergency due to epistaxis (group 1) and a group composed of patients with other symptoms (group 2)...
August 22, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28838291/zero-valent-iron-supported-on-nitrogen-doped-carbon-xerogel-as-catalysts-for-the-oxidation-of-phenol-by-fenton-like-system
#4
S A Messele, O S G P Soares, J J M Órfão, C Bengoa, J Font
Nitrogen-free and nitrogen-doped carbon xerogel materials, from urea and melamine precursors, were prepared at different pH and evaluated as adsorbents/catalysts in the removal of phenol. Then ZVI was supported on these carbon xerogel materials and its activity was again evaluated for phenol removal by adsorption and catalytic wet peroxide oxidation (CWPO). The prepared samples were characterized by N2 adsorption at -196 °C, pH at the point of zero charge (pHPZC) and elemental analysis. The textural properties of the N-free and N-doped carbon xerogels are strongly influenced by the pH of the preparation solution and precursor used...
August 25, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#5
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28614516/coordinated-care-for-tuberculosis-data-registration-and-implementation-of-a-computerized-system
#6
Nathalia Halax Orfão, Nathalia Yukie Crepaldi, Maria Eugênia Firmino Brunello, Rubia Laine de Paula Andrade, Aline Aparecida Monroe, Antonio Ruffino-Netto, Tereza Cristina Scatena Villa
Objective: to analyze sources of data for tuberculosis (TB) before and after the implementation of the Computerized System to Record Care for TB in Ribeirão Preto - SP. Method: Intervention, descriptive-analytical epidemiological study. Data was collected from secondary sources using a structured form, and analyzed using Chi-squared or Fisher's Exact Test, with a significance level of 5%. Results: We found an association between the period before implementation of the system and placing the Directly Observed Treatment Card in the file, and registration of instructions for the return visit by the nursing team...
June 2017: Ciência & Saúde Coletiva
https://www.readbyqxmd.com/read/28597680/fishbone-impaction-in-the-colon
#7
Armando Peixoto, Marco Silva, Branca Órfão, Guilherme Macedo
Postoperative benign biliary stricture in the anastomotic site is one of the most common complications of biliary-enteric anastomosis, with a rate of 6.87% after 2-13 years of follow-up. If untreated, biliary strictures can induce other complications such as recurrent cholangitis, intrahepatic stones, pancreatitis and secondary biliary cirrhosis. We report our experience with extracorporeal shock wave lithotripsy (ESWL) in a patient with a massive symptomatic stone proximal to an anastomotic biliary stricture...
June 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28498784/depth-of-response-in-multiple-myeloma-a-pooled-analysis-of-three-pethema-gem-clinical-trials
#8
Juan-Jose Lahuerta, Bruno Paiva, Maria-Belen Vidriales, Lourdes Cordón, Maria-Teresa Cedena, Noemi Puig, Joaquin Martinez-Lopez, Laura Rosiñol, Norma C Gutierrez, María-Luisa Martín-Ramos, Albert Oriol, Ana-Isabel Teruel, María-Asunción Echeveste, Raquel de Paz, Felipe de Arriba, Miguel T Hernandez, Luis Palomera, Rafael Martinez, Alejandro Martin, Adrian Alegre, Javier De la Rubia, Alberto Orfao, María-Victoria Mateos, Joan Blade, Jesus F San-Miguel
Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively)...
September 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28467808/a-systematic-approach-for-peptide-characterization-of-b-cell-receptor-in-chronic-lymphocytic-leukemia-cells
#9
Paula Díez, Nieves Ibarrola, Rosa M Dégano, Quentin Lécrevisse, Arancha Rodriguez-Caballero, Ignacio Criado, Wendy G Nieto, Rafael Góngora, Marcos González, Julia Almeida, Alberto Orfao, Manuel Fuentes
A wide variety of immunoglobulins (Ig) is produced by the immune system thanks to different mechanisms (V(D)J recombination, somatic hypermutation, and antigen selection). The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance to developing targeted vaccines or treatments for specific diseases or infections. Thus, genomics and proteomics techniques (such as Next-Generation Sequencing (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig sequencing and serum Ig peptide profiling in a high-throughput manner...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419441/detailed-immunophenotyping-of-b-cell-precursors-in-regenerating-bone-marrow-of-acute-lymphoblastic-leukaemia-patients-implications-for-minimal-residual-disease-detection
#10
Prisca M J Theunissen, Lukasz Sedek, Valerie De Haas, Tomasz Szczepanski, Alita Van Der Sluijs, Ester Mejstrikova, Michaela Nováková, Tomas Kalina, Quentin Lecrevisse, Alberto Orfao, Arjan C Lankester, Jacques J M van Dongen, Vincent H J Van Der Velden
Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages...
July 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28385786/host-virus-and-pneumococcus-specific-immune-responses-in-high-count-monoclonal-b-cell-lymphocytosis-and-chronic-lymphocytic-leukemia-implications-for-disease-progression
#11
Ignacio Criado, Santiago Muñoz-Criado, Arancha Rodríguez-Caballero, Wendy G Nieto, Alfonso Romero, Paulino Fernández-Navarro, Miguel Alcoceba, Teresa Contreras, Marcos González, Alberto Orfao, Julia Almeida
Patients diagnosed with chronic lymphocytic leukemia (CLL) display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high- (n=29) count monoclonal B-cell lymphocytosis versus healthy donors (n=91)...
July 2017: Haematologica
https://www.readbyqxmd.com/read/28365329/lot-to-lot-stability-of-antibody-reagents-for-flow-cytometry
#12
Sebastian Böttcher, Vincent H J van der Velden, Neus Villamor, Matthias Ritgen, Juan Flores-Montero, Hugo Murua Escobar, Tomas Kalina, Monika Brüggemann, Georgiana Grigore, Marta Martin-Ayuso, Quentin Lecrevisse, Carlos E Pedreira, Jacques J M van Dongen, Alberto Orfao
The fluorescence detected using fluorochrome-labelled monoclonal antibodies depends not only on the abundance of the target antigen, but amongst many other factors also on the effective fluorochrome-to-antibody ratio. The diagnostic approach of the EuroFlow consortium relies on reproducible fluorescence intensities over time. A capture bead system for mouse immunoglobulin light chains was utilized to compare the mean fluorescence intensity of 1323 consecutive antibody lots to the currently used lot of the same monoclonal antibody...
March 30, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28341440/optimization-and-testing-of-dried-antibody-tube-the-euroflow-lst-and-pidot-tubes-as-examples
#13
V H J van der Velden, J Flores-Montero, Martin Perez, Marta Martin-Ayuso, Oliver Crespo, Elena Blanco, Tomas Kalina, Jan Philippé, Carolien Bonroy, Maaike de Bie, Jeroen Te Marvelde, Cristina Teodosio, Alba Corral Mateos, Veronika Kanderová, Mirjam van der Burg, Dennis Van Hoof, Jacques J M van Dongen, Alberto Orfao
Within EuroFlow, we recently developed screening tubes for hematological malignancies and immune deficiencies. Pipetting of antibodies for such 8-color 12-marker tubes however is time-consuming and prone to operational mistakes. We therefore evaluated dried formats of the lymphocytosis screening tube (LST) and of the primary immune deficiency orientation tube (PIDOT). Both tubes were evaluated on normal and/or on patient samples, comparing the mean fluorescence intensity of specific lymphocyte populations. Our data show that the dried tubes and liquid counterparts give highly comparable staining results, particularly when analyzed in multidimensional plots...
March 21, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28254862/advances-in-the-classification-and-treatment-of-mastocytosis-current-status-and-outlook-toward-the-future
#14
REVIEW
Peter Valent, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Wolfgang R Sperr, Luis Escribano, Tracy I George, Hanneke C Kluin-Nelemans, Celalettin Ustun, Massimo Triggiani, Knut Brockow, Jason Gotlib, Alberto Orfao, Lawrence B Schwartz, Sigurd Broesby-Olsen, Carsten Bindslev-Jensen, Petri T Kovanen, Stephen J Galli, K Frank Austen, Daniel A Arber, Hans-Peter Horny, Michel Arock, Dean D Metcalfe
Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28222384/direct-catalytic-production-of-sorbitol-from-waste-cellulosic-materials
#15
Lucília Sousa Ribeiro, José J de Melo Órfão, Manuel Fernando Ribeiro Pereira
Cotton wool, cotton textile, tissue paper and printing paper, all potential waste cellulosic materials, were directly converted to sorbitol using a Ru/CNT catalyst in the presence of H2 and using only water as solvent, without any acids. Conversions up to 38% were attained for the raw substrates, with sorbitol yields below 10%. Ball-milling of the materials disrupted their crystallinity, allowing reaching 100% conversion of cotton wool, cotton textile and tissue paper after 4h, with sorbitol yields around 50%...
May 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28214624/effect-of-cobalt-loading-on-the-solid-state-properties-and-ethyl-acetate-oxidation-performance-of-cobalt-cerium-mixed-oxides
#16
M Konsolakis, S A C Carabineiro, G E Marnellos, M F Asad, O S G P Soares, M F R Pereira, J J M Órfão, J L Figueiredo
Cobalt-cerium mixed oxides were prepared by the wet impregnation method and evaluated for volatile organic compounds (VOCs) abatement, using ethyl acetate (EtAc) as model molecule. The impact of Co content on the physicochemical characteristics of catalysts and EtAc conversion was investigated. The materials were characterized by various techniques, including N2 adsorption at -196°C, scanning electron microscopy (SEM), X-ray diffraction (XRD), H2-temperature programmed reduction (H2-TPR) and X-ray photoelectron spectroscopy (XPS) to reveal the structure-activity relationship...
June 15, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28104919/next-generation-flow-for-highly-sensitive-and-standardized-detection-of-minimal-residual-disease-in-multiple-myeloma
#17
J Flores-Montero, L Sanoja-Flores, B Paiva, N Puig, O García-Sánchez, S Böttcher, V H J van der Velden, J-J Pérez-Morán, M-B Vidriales, R García-Sanz, C Jimenez, M González, J Martínez-López, A Corral-Mateos, G-E Grigore, R Fluxá, R Pontes, J Caetano, L Sedek, M-C Del Cañizo, J Bladé, J-J Lahuerta, C Aguilar, A Bárez, A García-Mateo, J Labrador, P Leoz, C Aguilera-Sanz, J San-Miguel, M-V Mateos, B Durie, J J M van Dongen, A Orfao
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign...
October 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28079251/maturation-associated-gene-expression-profiles-along-normal-human-bone-marrow-monopoiesis
#18
Fabiana V Mello, Liliane R Alves, Marcelo G P Land, Cristina Teodósio, María-Luz Sanchez, Paloma Bárcena, Rodrigo T Peres, Carlos E Pedreira, Elaine S Costa, Alberto Orfao
Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis...
February 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28004597/functional-proteomic-insights-in-b-cell-chronic-lymphocytic-leukemia
#19
REVIEW
Paula Díez, Rafael Góngora, Alberto Orfao, Manuel Fuentes
B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease. Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described...
February 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28003549/first-in-class-inhibitor-of-the-t-cell-receptor-for-the-treatment-of-autoimmune-diseases
#20
Aldo Borroto, Diana Reyes-Garau, M Angeles Jiménez, Esther Carrasco, Beatriz Moreno, Sara Martínez-Pasamar, José R Cortés, Almudena Perona, David Abia, Soledad Blanco, Manuel Fuentes, Irene Arellano, Juan Lobo, Haleh Heidarieh, Javier Rueda, Pilar Esteve, Danay Cibrián, Ana Martinez-Riaño, Pilar Mendoza, Cristina Prieto, Enrique Calleja, Clara L Oeste, Alberto Orfao, Manuel Fresno, Francisco Sánchez-Madrid, Antonio Alcamí, Paola Bovolenta, Pilar Martín, Pablo Villoslada, Antonio Morreale, Angel Messeguer, Balbino Alarcon
Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM...
December 21, 2016: Science Translational Medicine
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