Asunto(s)
Genes Virales , Marcadores Genéticos , Vectores Genéticos/efectos adversos , Receptor de Factor de Crecimiento Nervioso/análisis , Retroviridae/genética , Animales , Trasplante de Médula Ósea , Perros , Humanos , Leucemia/etiología , Leucemia/prevención & control , Ratones , Ratas , Transducción GenéticaRESUMEN
Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2 receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain which binds IL-2 with intermediate affinity and plays a crucial role in transducing the message to the cell. For this purpose, we tested highly enriched leukemic HC from six hairy cell leukemia patients for the presence of IL-2R transcripts and for the expression of the p55 and p75 IL-2R chains on their surface membrane by flow cytometry and immunoprecipitation analyses. The functional role of IL-2 in the regulation of HC proliferation was also investigated. Our results indicate that freshly isolated HC express detectable messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A mixture of two specific mAb was able to immunoprecipitate detectable amounts of p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of several concentrations of IL-2 a low proliferative response was observed. Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75 IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide direct evidence of the expression of different IL-2 receptors on leukemic HC and suggest that these molecules might play a role in leukemic cell growth.
Asunto(s)
Leucemia de Células Pilosas/patología , Receptores de Interleucina-2/fisiología , Adulto , Anticuerpos , División Celular/fisiología , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Femenino , Citometría de Flujo , Expresión Génica/genética , Humanos , Interleucina-2/farmacología , Leucemia de Células Pilosas/genética , Sustancias Macromoleculares , Masculino , Persona de Mediana Edad , Pruebas de Precipitina , ARN Mensajero/genética , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/inmunología , Transcripción Genética/genética , Células Tumorales CultivadasRESUMEN
Two-dimensional electrophoretic analysis (2D-PAGE) of cell surface human DP and DR class II antigens identified a glycoprotein, designated pX, that is associated at the cell surface with DP but not DR class II antigen in activated T, B and NK lymphocytes but not in resting B lymphocytes, Raji B lymphoma cells, activated thymic epithelial cells or activated monocytes. pX is a heavily glycosylated protein with an apparent molecular mass spanning between 38 kDa and 22 kDa, that is reduced, after deglycosylation with Endo-F, to 22 kDa. The pX structure appears nonpolymorphic and independent of DP polymorphism, as suggested by 2D-PAGE migrational pattern of 125I-labelled Endo-F deglycosylated DP immunoprecipitates from T cells blasts derived from four donors with different DP allotypes. The apparent absence of polymorphism of pX is further suggested by two-dimensional peptide mapping of a single spot derived from 2D-PAGE of 125I-labelled DP deglycosylated immunoprecipitates from two donors.
Asunto(s)
Antígenos HLA-DP/metabolismo , Activación de Linfocitos , Subgrupos Linfocitarios/inmunología , Glicoproteínas de Membrana/metabolismo , Linfocitos B/química , Linfocitos B/inmunología , Células Cultivadas , Glicosilación , Antígenos HLA-DP/biosíntesis , Antígenos HLA-DP/aislamiento & purificación , Humanos , Interfase/inmunología , Subgrupos Linfocitarios/química , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/aislamiento & purificación , Peso Molecular , Unión Proteica/inmunología , Linfocitos T/química , Linfocitos T/inmunologíaRESUMEN
A general feature of cancer growth is the cellular competition for available nutrients. This is also the case for tumor cords, neoplasms forming cylindrical structures around blood vessels. Experimental data show that, in their avascular phase, cords grow up to a limit radius of about 100 microm, reaching a quasi-steady-state characterized by a necrotized area separating the tumor from the surrounding healthy tissue. Here we use a set of rules to formulate a model that describes how the dynamics of cord growth is controlled by the competition of tumor cells among themselves and with healthy cells for the acquisition of essential nutrients. The model takes into account the mechanical effects resulting from the interaction between the multiplying cancer cells and the surrounding tissue. We explore the influence of the relevant parameters on the tumor growth and on its final state. The model is also applied to investigate cord deformation in a region containing multiple nutrient sources and to predict the further complex growth of the tumor.
RESUMEN
The effect of rIL-4 on CD69 antigen expression induced by rIL-2 or by rINF-alpha on human resting NK cells and CD3+, CD4-, CD8- T lymphocytes has been investigated. rIL-4 drastically inhibited CD69 antigen expression induced by rIL-2 in both cell types. In contrast, rIL-4 did not alter rINF-alpha-induced CD69 antigen expression. Consistent results were obtained evaluating the cytolytic activity of NK cells against the Raji target cell line: rINF-alpha-induced lytic activity was not inhibited by rIL-4, while rIL-2-induced lytic activity was drastically inhibited. Proliferative activity of NK cells induced by rIL-2, in contrast, was only slightly reduced by rIL-4. rIL-4 did not alter the expression of the beta chain of IL-2 receptor, evaluated in NK cells by indirect immunofluorescence. Expression of the alpha chain of IL-2 receptor could not be detected in NK cells by indirect immunofluorescence. It can therefore be suggested that the selective inhibitory effect of rIL-4 on rIL-2-induced activation of NK cells is not mediated by downregulation of alpha and beta chains of IL-2 receptor.
Asunto(s)
Antígenos CD/biosíntesis , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Interferón-alfa/farmacología , Interleucina-2/farmacología , Interleucina-4/farmacología , Células Asesinas Naturales/efectos de los fármacos , Subgrupos Linfocitarios/efectos de los fármacos , Antígenos de Diferenciación de Linfocitos T/análisis , Complejo CD3 , Antígenos CD4/análisis , Antígenos CD8/análisis , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Asesinas Naturales/inmunología , Lectinas Tipo C , Subgrupos Linfocitarios/inmunología , Receptores de Antígenos de Linfocitos T/análisis , Proteínas Recombinantes/farmacologíaRESUMEN
The effect of rIL-12 on induction of CD69 antigen expression and cytolytic activity in purified human NK cells was evaluated in comparison to the effects of rIL-2 and rIFN-alpha. It was found that rIL-12 directly induced CD69 antigen expression in NK cells, although the period of incubation required by rIL-12 was longer than the period required by rIL-2 or by rIFN-alpha. Similarly, the cytolytic activity induced by rIL-12 in NK cells against the NK-resistant target cell line Raji was consistently lower than the cytolytic activity induced by rIL-2 or rIFN-alpha when measured after 6 hr of incubation, and increased during the following 18 hr of incubation. To compare the involvement of tyrosin kinases in activation of NK cells induced by rIL-2, rIL-12, and rIFN-alpha, the effect of the specific inhibitor of tyrosin kinases, genistein, was evaluated on induction of CD69 antigen expression and lytic function mediated by the three cytokines. It was found that genistein inhibited CD69 antigen expression induced by rIL-2 and by rIL-12, but not that induced by rIFN-alpha. Unlike the effect on CD69 antigen expression, the cytolytic activity induced by all three cytokines was inhibited by genistein. These results, together with the finding that CD69 antigen expression induced by rIL-2 but not by rIL-12 or rIFN-alpha was inhibited by addition of rIL-4, strongly suggest that IL-2, IL-12, and IFN-alpha mediate their effects, leading to induction of CD69 antigen expression through different activation pathways.
Asunto(s)
Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Interferón-alfa/farmacología , Interleucina-2/farmacología , Interleucinas/farmacología , Isoflavonas/farmacología , Células Asesinas Naturales/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Células Cultivadas , Citotoxicidad Inmunológica/efectos de los fármacos , Genisteína , Humanos , Interleucina-12 , Células Asesinas Naturales/inmunología , Lectinas Tipo C , Proteínas Recombinantes/farmacologíaAsunto(s)
Antígenos de Diferenciación de Linfocitos T/análisis , Interferón Tipo I/farmacología , Interferón gamma/farmacología , Células Asesinas Naturales/inmunología , Factor de Necrosis Tumoral alfa/farmacología , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/genética , Línea Celular , Citotoxicidad Inmunológica/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas In Vitro , Células Asesinas Naturales/efectos de los fármacos , Lectinas Tipo C , Fosforilación , Proteínas Recombinantes/farmacologíaRESUMEN
Este estudo avaliou, de maneira duplo-cega a eficacia analgesica e tolerancia a administracao de dose unica de acetaminofen (1.000 mg), acido acetilsalicilico (1.000 mg) e placebo, em 90 pacientes com dor pos-episiotomia. Os parametros analisados, respectivamente intensidade de dor, alivio da dor, necessidade ou nao de analgesicos suplementares, revelaram eficacia comparavel dos agentes terapeuticos,ambos se mostrando estatisticamente superiores ao placebo, durante as quatro horas de avaliacao As drogas foram bem toleradas