The original discovery of NK cells approximately 40 yr ago was based on their unique capability to kill tumor cells without prior sensitization or priming, a process named natural cytotoxicity. Since ...then, several studies have documented that NK cells can kill hematopoietic and nonhematopoietic cancer cells. NK cells also recognize and kill cells that have undergone viral infections. Besides natural cytotoxicity, NK cells are also major effectors of antibody-dependent cell cytotoxicity (ADCC). Therefore, NK cells are well "armed" to recognize and mount immune responses against "insults" that result from cell transformation and viral infections. Because of these attributes, an essential role of NK cells in tumor surveillance was noted. Indeed, several studies have shown a correlation between impaired NK cell cytotoxicity and a higher risk of developing cancer. This evidence led to the idea that cancer initiation and progress is intimately related to an abnormal or misdirected immune response. Whereas all these ideas remain current, it is also true that NK cells represent a heterogeneous population with different abilities to secrete cytokines and to mediate cytotoxic functions. In addition, recent data has shown that NK cells are prone to suffer epigenetic modifications resulting in the acquisition of previously unrecognized attributes such as memory and long-term survival. Such NK cells, referred as "adaptive" or "memory-like," also display effector functions that are not necessarily equal to those observed in conventional NK cells. Given the new evidence available, it is essential to discuss the conceptual reasoning and misconceptions regarding the role of NK cells in immune surveillance and immunotherapy.
•Two novel mutations in ZAP70 in a patient with an early-onset immunodeficiency are described.•Both mutations resulted in partial absence of ZAP-70 protein and were ineffective to promote ...TCR-dependent signals.•Our findings extend the genetic etiology and molecular characterization of ZAP-70 mutations that lead to early onset immunodeficiency.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per ...million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia.
NK cells have unique attributes to react towards cells undergoing malignant transformation or viral infection. This reactivity is regulated by activating or inhibitory germline encoded receptors. An ...impaired NK cell function may result from an aberrant expression of such receptors, a condition often seen in patients with hematological cancers. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide and NK cells have emerged as crucial targets for developing immunotherapies. However, there are important gaps concerning the phenotype and behavior of NK cells during emergence of ALL. In this study we analyze the phenotype and function of NK cells from peripheral blood in pediatric patients with ALL at diagnosis. Our results showed that NK cells exhibited an altered phenotype highlighted by a significant reduction in the overall expression and percent representation of activating receptors compared to age-matched controls. No significant differences were found for the expression of inhibitory receptors. Moreover, NK cells with a concurrent reduced expression in various activating receptors, was the dominant phenotype among patients. An alteration in the relative frequencies of NK cells expressing NKG2A and CD57 within the mature NK cell pool was also observed. In addition, NK cells from patients displayed a significant reduction in the ability to sustain antibody-dependent cellular cytotoxicity (ADCC). Finally, an aberrant expression of activating receptors is associated with the phenomenon of leukemia during childhood.
El nogal pecanero (Carya illinoinensis) es uno de los cultivos más importantes de la Comarca Lagunera. La deficiencia de zinc (Zn) es uno de los principales problemas que limitan su productividad. La ...nanotecnología incluye materiales nutrimentales con los que se pueden sustituir fertilizantes convencionales con variado efecto en rendimiento, calidad biofísica y nutracéutica en el fruto. Los efectos de la aplicación foliar de nanopartículas de ZnO en nogal pecanero variedad Western fueron evaluados mediante dosis de Zn con los siguientes tratamientos: control, 4000 (ZnSO4), 2000 (nps ZnO), y 4000 (nps ZnO) mg L-1. El diseño experimental fue en bloques al azar con cuatro repeticiones. Las variables evaluadas en fruto y árbol fueron: rendimiento, número de nueces kg-1, largo y ancho de nuez, concentración de Zn en foliolos, ácidos grasos, proteína cruda, porcentaje de grasa y humedad. Se observó diferencia significativa en rendimiento y nivel de Zn en los foliolos, donde el mejor tratamiento fue 4000 mg L-1 de nanopartículas de ZnO, mientras que para la variable largo de nuez se observó diferencia significativa, siendo inferior el tratamiento de 4000 mg L-1 de ZnSO4. En las variables nutracéuticas, el contenido de ácidos grasos evaluado mediante el contenido de grasas saturadas (C16:0 y C18:0) mostró cambios altamente significativos, siendo el tratamiento con la dosis de 4000 mg L-1 de nanopartículas el que tuvo mayor porcentaje. Los ácidos grasos insaturados (C18:1 y C18:3) mostraron diferencias significativas, siendo los tratamientos evaluados con nanopartículas los que tuvieron un porcentaje inferior. El contenido de proteína también mostró diferencias altamente significativas, siendo el tratamiento control y el químico a base de ZnSO4 los tratamientos superiores. Las nanopartículas pueden ser usadas para mejorar el rendimiento y abastecer el contenido de Zn al cultivo, pero la calidad de fruto se ve afectada desde el punto de vista nutricional.
One of the most frequent complications of cardiac surgery is the perioperative myocardial infarction (PMI). Incidence of PMI shows a wide variation because an accurate detection of this complication ...is difficult in the early postoperative stage. The objectives of the present study were to determine in our population of patients the incidence of PMI during the first seventy two hours after cardiac surgery as well as associations among the accepted criteria to diagnose this complication.
One hundred sixty four adults patients undergoing elective cardiac surgery were studied. With baselines preoperative studies, serial electrocardiographic, enzymatic (determination of serum creatine kinase isoenzyme (CK-MB) and echocardiographic studies were performed during the first 72 hours after cardiac surgery. Diagnosis of PMI was established with two or all the three positive criteria electrocardiographic (ECG), enzymatic (CK-MB) and echocardiographic (ECHO).
In 24 (15%) patients PMI was diagnosed. In this group 13 (54%) all the three criteria were positive. In 8 (33%) patients CK-MB and ECHO were positive. In 3 (13%) patients CK-MB and ECG were positive.
In our population the incidence of PMI (15%) is agree with the reported in previous studies. In most of cases of PMI all the three diagnostic criteria are positive. When diagnosis is established only with two criteria, in most of cases these are CK-MB and ECHO.
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