Destruction of Rat Islet Cell Monolayers by Cytokines: Synergistic Interactions of Interferon-γ, Tumor Necrosis Factor, Lymphotoxin, and Interleukin 1

An assay was developed to detect the cytotoxic effects of cytokines on rat pancreatic islet cells in monolayer culture. Cell lysis was detected by a 51Cr-release assay after 4 days of incubation with various cytokines. When tested alone, murine (rat and mouse) interferon-γ (mIFN-γ) produced a small dose-dependent lysis of islet cells; human IFN-γ, mouse IFN-α/β, interleukins 1 and 2 (IL-1 and IL-2), tumor necrosis factor (TNF), and lymphotoxin (LT) were inactive. When added together, the following combinations of cytokines showed synergistic cytotoxic effects: TNF (or LT) plus IL-1, TNF (or LT) plus mIFN-γ, and IL-1 plus mIFN-γ. These results indicate that the cytokine products of mononuclear cells of the immune system, IFN-γ, TNF, LT, and IL-1 have strong synergistic cytotoxic effects on islet cells and therefore may act as direct chemical mediators of islet β-cell destruction in type I (insulin-dependent) diabetes.</jats:p

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

We compared the cytotoxic effects to islet cells of lymphoid cells from diabetic and diabetes-resistant (DR) BioBreeding/Worcester (BB/W) rats with a 51Cr-release assay to detect lysis of normal rat islet cells. Splenic lymphoid cells from diabetic rats were more cytotoxic to islet cells (11.3 ± 3.8%) than were lymphoid cells from DR rats (4.0 ± 2.6%). This difference was amplified by incubating the lymphoid cells for 20 h with 5 μg/ml concanavalin A (ConA); islet cell lysis was 39.3 ± 4.5% by ConA-activated diabetic cells and 9.6 ± 2.7% by ConA-activated DR cells. The cytotoxic lymphoid cells were identified as natural killer (NK) cells, because treatment of diabetic lymphoid cells with anti-asialo GM1 serum and complement selectively removed a monoclonal antibody-defined subset of NK cells (OX8+), and the NK-depleted lymphoid cells were not cytotoxic to either islet or NK-sensitive YAC-1 cells, even after culture with ConA. Of several lymphokine products of ConA-stimulated lymphoid cells, interleukin 2 (IL-2), but not interleukin 1 or interferon-γ, significantly activated splenic lymphoid cells cytotoxic to islet cells, and the lymphoid cells from diabetic rats were more sensitive to IL-2 (3 U/ml) than were the cells from DR rats (30 U/ml). This study reveals the presence of ConA- and IL-2-responsive islet cytotoxic NK cells in the diabetic BB/W rat and suggests that IL-2 activation of NK cells may contribute to islet β-cell destruction and diabetes in this animal.</jats:p

Thrombotic thrombocytopenic purpura subsequent to acute myelogenous leukemia chemotherapy

A woman in complete remission from acute myeloblastic leukemia developed thrombotic thrombocytopenic purpura (TTP) subsequent to the third intensive consolidation cycle of cytosine arabinoside and daunorubicin chemotherapy. The constellation of clinical manifestations indicative of TTP were recognized only in retrospect, as they were initially attributed to more usual complications of bone marrow‐ablative chemotherapy. The manifestations, probably fueled by numerous red cell and platelet transfusions, increased at the time of recovery of hematopoiesis. At postmortem examination, characteristic microvascular lesions were found in most organs. Similar thrombotic microangiopathy has been described with mitomycin‐based chemotherapy regimens and with the combination of cisplatin, vinblastine, and bleomycin. Successful management of this serious complication of chemotherapy requires increased awareness and earlier recognition

Bocetos-AR168-201701

El curso de Bocetos es un curso electivo de la carrera de Arquitectura de carácter teórico- práctico dirigido a estudiantes a partir del tercer ciclo que busca reforzar las competencias generales de Pensamiento innovador Comunicación escrita y Manejo de la Información y las competencias específicas de Gestión de su actividad y Proyecto Arquitectónico competencias ya adquiridas por los alumnos al momento de inicio de este curso.El objetivo del curso consiste en dar a los estudiantes herramientas que le permitan expresar de manera sintética dibujos donde pueda comunicar las características propias de un objeto un lugar un edificio. Se suma a esto la necesidad de realizarlo en poco tiempo y de forma clara destacando los aspectos más importantes