Intraclonal diversity in a Sezary syndrome with a differential response to 2‐deoxycoformycin of the two lymphoma cell populations

Br J Haematol. 2002 Dec;119(3):629-33. Intraclonal diversity in a Sezary syndrome with a differential response to 2-deoxycoformycin of the two lymphoma cell populations. Granjo E, Lima M, Lopes JM, Cunha N, Teixeira Mdos A, Santos F, Candeias J, Resende C, Santos AH, Balanzategui A, Orfão A, Matutes E. Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. [email protected] Abstract We report a case of Sezary syndrome with two abnormal CD4+ T-cell populations detected in the peripheral blood by flow cytometry immunophenotyping and DNA cell content, suggesting a biclonal T-cell lymphoproliferative disorder. Despite these findings, molecular analysis of the T-cell receptor genes was consistent with a monoclonal T-cell proliferation, supporting the existence of intraclonal diversity rather than a true biclonal disease. The patient achieved a transient response with 2-deoxycoformycin, with a selective decrease of the larger/hyperploid T-cell population; later on, an increased representation of this T-cell population was observed concomitantly with clinical relapse. PMID: 12437636 [PubMed - indexed for MEDLINE

Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56‐/+dim chronic natural killer cell large granular lymphocytosis.

Am J Pathol. 2004 Oct;165(4):1117-27. Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56-/+dim chronic natural killer cell large granular lymphocytosis. Lima M, Almeida J, Montero AG, Teixeira Mdos A, Queirós ML, Santos AH, Balanzategui A, Estevinho A, Algueró Mdel C, Barcena P, Fonseca S, Amorim ML, Cabeda JM, Pinho L, Gonzalez M, San Miguel J, Justiça B, Orfão A. Serviço de Hematologia, Unidade de Citometria, Hospital Geral de Santo António, Rua D Manuel II, s/n, 4099-001 Porto, Portugal. [email protected]. Abstract Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56(+), NK cells in the absence of any clonal marker are present in the peripheral blood. In the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56(+) NK cells, CD56(-/+dim) NK cells were granzyme B(+), CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright), CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56(-/+dim), they were CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous), CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(-/+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56(-/+dim) NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. In summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases. PMID: 15466379 [PubMed - indexed for MEDLINE]PMCID: PMC161863

Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

Altres ajuts: This work was partially supported by[...] , CIBERONC-CB16/12/00233, and "Una manera de hacer Europa" (Innocampus; CEI-2010-1-0010)". M.G.-A., I.P.-C., and C.J. are supported by the Fundación Española de Hematología y Hemoterapia (FEHH, co-funded by Fundación Cris in the latter case), A.M. by the European Social Fund and the Spanish Education Council through the University of Salamanca, [...]. All Spanish funding is co-sponsored by the European Union FEDER program.Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers

Anti-TRBC1 antibody-based flow cytometric detection of T-cell clonality: standardization of sample preparation and diagnostic implementation

Simple Summary The anti-TRBC1 antibody JOVI-1 has recently been identified as a flow cytometry marker potentially useful for assessment of T-cell clonality. The aim of this study was to optimize a flow cytometric method for routine use of anti-TRBC1 to assess T-cell clonality and validate it in a large series of normal and pathological samples. Our results showed that the best resolution to accurately identify TRBC1(+) cells was achieved by adding the CD3 antibody either simultaneously or after TRBC1. In addition, TRBC1(+)/TRBC1(-) ratios within different T alpha beta-cell subsets are provided as expected reference ranges for polyclonal T-cells. Based on the optimized approach here proposed, we detected monoclonal T alpha beta-cell populations with high specificity (96%) and a high analytical sensitivity/level of detection (<= 10(-4)), when clonal T-cells exhibited immunophenotypic aberrancies. These findings further support and extend previous observations about the utility of TRBC1 for the diagnostic screening and monitoring of clonal T alpha beta-cell populations.A single antibody (anti-TRBC1; JOVI-1 antibody clone) against one of the two mutually exclusive T-cell receptor beta-chain constant domains was identified as a potentially useful flow-cytometry (FCM) marker to assess T alpha beta-cell clonality. We optimized the TRBC1-FCM approach for detecting clonal T alpha beta-cells and validated the method in 211 normal, reactive and pathological samples. TRBC1 labeling significantly improved in the presence of CD3. Purified TRBC1(+) and TRBC1(-) monoclonal and polyclonal T alpha beta-cells rearranged TRBJ1 in 44/47 (94%) and TRBJ1+TRBJ2 in 48 of 48 (100%) populations, respectively, which confirmed the high specificity of this assay. Additionally, TRBC1(+)/TRBC1(-) ratios within different T alpha beta-cell subsets are provided as reference for polyclonal cells, among which a bimodal pattern of TRBC1-expression profile was found for all TCRV beta families, whereas highly-variable TRBC1(+)/TRBC1(-) ratios were observed in more mature vs. naive T alpha beta-cell subsets (vs. total T-cells). In 112/117 (96%) samples containing clonal T alpha beta-cells in which the approach was validated, monotypic expression of TRBC1 was confirmed. Dilutional experiments showed a level of detection for detecting clonal T alpha beta-cells of <= 10(-4) in seven out of eight pathological samples. These results support implementation of the optimized TRBC1-FCM approach as a fast, specific and accurate method for assessing T-cell clonality in diagnostic-FCM panels, and for minimal (residual) disease detection in mature T alpha beta(+) leukemia/lymphoma patients.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Co-creating, co-producing and connecting: Museum practice today.

This is the peer reviewed version of the following article: Barnes, P., & McPherson, G. (2019). Co‐Creating, Co‐producing and Connecting: Museum Practice Today. Curator: The Museum Journal, 62(2), 257-267., which has been published in final form at https://doi.org/10.1111/cura.12309. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingWe argue in this paper that museums have become hybrid spaces, where consumers look and challenge what they see; they form part of what they see; with some aspects of exhibitions now co‐created and co‐produced by the consumer (Kershaw et al. 2018; Solis 2012). This paper draws on an example from a group that we worked with using performance as a tool to engage a ‘hard to reach’ or ‘socially excluded’ groups. We conclude that by allowing audiences to co‐create and co‐produce exhibitions and performance; this can turn the museum rhetoric of community engagement into practice and create a space that is truly inclusive for the communities it serves. We demonstrate how the possibility of seeing museums as hybrid spaces, which can adapt, can be used for education and entertainment, and how that has in turn led to the transformation of people's lives in a previously socially excluded community

Recolección de Envases Vacíos de Vidrio, Clasificación, Procesamiento y Venta de Calcín

El reciclaje de envases de vidrios no retornables es una alternativa ante el alza de emisiones de CO2 a la afmosfera, por la fabricación de nuevos envases de vidrios con materia prima virgen la misma que impacta directamente sobre el calentamiento global afectando el medio ambiente y la salud de la población el presente proyecto nos lleva a analizar la factibilidad económica de implantar una planta procesadora de envases de vidrio, que abarque los procesos desde la recolcción, procesamiento y hasta la venta de calcín a los productores de envases de vidrio de este modo se pretende sastifacer la demanda de calcín que existe en la actualidad.GuayaquilMagíster en Gestión de Proyecto

Recolección de Envases Vacíos de Vidrio, Clasificación, Procesamiento y Venta de Calcín

El reciclaje de envases de vidrios no retornables es una alternativa ante el alza de emisiones de CO2 a la afmosfera, por la fabricación de nuevos envases de vidrios con materia prima virgen la misma que impacta directamente sobre el calentamiento global afectando el medio ambiente y la salud de la población el presente proyecto nos lleva a analizar la factibilidad económica de implantar una planta procesadora de envases de vidrio, que abarque los procesos desde la recolcción, procesamiento y hasta la venta de calcín a los productores de envases de vidrio de este modo se pretende sastifacer la demanda de calcín que existe en la actualidad.GuayaquilMagíster en Gestión de Proyecto

Diseño del sistema de distribución primarío de la subestación chorrera de la empresa eléctrica los ríos c.a.

Resumen En el sistema eléctrico a nivel de distribución se puede presentar problemas de interrupciones las cuales pueden ser momentáneas o permanentes, estos fenómenos desmejoran la calidad del servicio eléctrico y causan grandes perjuicios económicos tanto a los usuarios como a las empresas distribuidoras. La evolución de la tecnología en especial de las cargas no lineales (equipo de electrónica de potencia), causa grandes problemas en el sistema eléctrico de distribución. A fin de evitar estos problemas causantes de la mala calidad del servicio eléctrico, es de suma importancia realizar el diseño del Sistema de Distribución Primario para escoger los equipos de protección mas adecuados a fin de llegar a tener un sistema confiable, seguro y que cumpla con todas las normas y reglamentos vigentes de Calidad del Servici