Myc overexpression brings out unexpected antiapoptotic effects of miR-34a.

Downregulation of microRNA-34a by Myc is known to be essential for tumorigenesis and improve tumor-cell survival. Conversely, upregulation of miR-34a by p53 is thought to enhance its acetylation and activity and contribute to the pro-apoptotic effects of this tumor suppressor. We sought to determine whether restoration of miR-34a levels in B-lymphoid cells with Myc overexpression would aid therapeutic apoptosis. Unexpectedly, delivery of miR-34a, which doesn't target p53 directly, severely compromised steady-state p53 levels. This effect was preceded and mediated by direct targeting of Myc, which sustained p53 protein levels via the Arf-Hdm2 pathway. As a result, in the presence of Myc, miR-34a inhibited p53-dependent bortezomib-induced apoptosis as efficiently as anti-p53 small interfering RNA. Conversely, inhibition of miR-34a using antisense RNA sensitized lymphoma cells to therapeutic apoptosis. Thus, in tumors with deregulated Myc expression, miR-34a confers drug resistance and could be considered a therapeutic target.

Identification of variables that influence brain-dead donors' family groups regarding refusal.

OBJECTIVE: To identify the variables that influenced brain-dead donor family groups to refuse donation. METHODS: The Tissue and Organ Procurement System in Venezuela designed a tool to register some phases of a family interview performed by transplant coordinators. This tool analyzed three phases. The first phase of the interview allowed the coordinator to evaluate the communication quality with the family group during a brain-death notification. The second phase assessed how families understood this notification, and the third phase identified the family grief sequence. Among the 186 interviews during 2007 to procure tissues and organs for transplantation, 37.63% (n = 70) concluded as family refusals. A retrospective study sought to analyze these results. RESULTS: The average time between notification of brain death and the first approach to the family was 8.78 hours. Setting a place for interviews was done in 91.10% of cases. Previous knowledge about donation was seen in only 53.33% of cases. The main phase of family grief identified was denial (80%). The five reasons for family denial were: absolute denial, family disagreement, uncertainty about the destination of the donated organs and tissues, fear about deformation of the donor's body, and lack of acceptance of brain death. CONCLUSIONS: Brain-death notification produced a deep sadness among family groups. There was a lack of knowledge regarding donation of tissues and organs. It was impossible to quantify the time needed by families to understand and accept brain death and to identify the grief sequence in order to avoid family refusals.

Movement ability of rye terminal neocentromeres.

Rye terminal neocentromeres were analyzed in various aspects. Plants with and without neocentromeres were crossed to determine the possible genetic control on their formation. The segregation obtained in our work is consistent with the hypothesis of two trans-acting genes determining neocentric activity in such a way that individuals with no neocentromeres at all would carry all non-activating alleles, whereas one activating allele might permit the activation of a few neocentromeres. Individuals with four activating alleles would show the maximum frequency of neocentromeres per cell. Anti-tubulin immunolabelling was used to visualize the interaction between the neocentromeres and the microtubules. In most cases an end-on interaction between neocentromeres and microtubules was observed, but a few neocentromeres were observed free of them. Spikes were irradiated at early meiosis to determine whether acentric fragments carrying subtelomeric heterochromatin were able to behave as neocentromeres. In no case were acentric fragments observed to form an extension polewards as they did in whole chromosomes. Broken chromosomes joined by a thin thread of chromatin to the centromeric region

Tuberculoma de ganglios basales: a propósito de un caso / Tuberculoma of glanglion basal: a purpose of a case

Se trata de escolar, femenina, de 7 años de edad, natural y procedente de la localidad de Petare, Edo. Miranda, Venezuela, que ingresa con signos de hipertensión endocraneana, con diagnóstico por estudios imagenológicos de: LOE en núcleos basales izquierdos e hidrocefalia obstructiva, ameritó colocación de sistema de derivación ventrículo peritoneal, con estabilización de condiciones clínicas. Se realiza biopsia por estereotaxia resultando la muestra no concluyente para precisar diagnóstico histopatológico, planificando Craneotomía parietal izquierda, extirpando aproximadamente 40 por ciento de la lesión. El diagnóstico histopatológico: Granuloma tuberculoso (Tubercoloma), se indica tratamiento (Isoniazida, Rifampicina y Pirazinamida), hasta la actualidad, con una reducción significativa de la lesión, y clínicamente asintomática. Se desea destacar las bondades de la estereotaxia, pero deben considerarse ciertas dificultades. Es importante resaltar las variables socioeconómicas y sanitarias que involucra esta patología, poco frecuente en el Sistema Nervioso Central (SNC) y que este caso seria el primero en reportarse con localización supratentorial en nuestro Centro

Revascularización cerebral mediante encéfalo arterio sinangiosis en el tratamiento de accidentes cerebrovasculares isquémicos: experiencia del Hospital de Niños J. M de Los Ríos: reporte de cuatro casos / Sinangiosis artherio brain in the treatment of ischemic cerebrovascular accidents: experience of the J. M de Los Ríos Hospital: report of 4 cases

Se reportaron los resultados de la encéfalo-arterio-sinangiosis en el tratamiento quirúrgico de la isquemia cerebral en el Hospital de Niños "J.M de Los Ríos". Caracas. Es liberada una arteria del cuero cabelludo (arteria temporal superficial) y puesta en contacto con la corteza cerebral, después de una craneotomía y apertura de la duramadre. Cuatro cirugías fueron realizadas en un período de dos años. Se analizaron los resultados, ventajas e indicaciones de este tipo de cirugía

Análisis de la implicación de los genes de supresión tumoral TP53, p16INK4, p21WAF1, RB1 y de las enzimas metabolizadoras de drogas en el desarrollo de tumores óseos en niños / Analysis of the involvement of the tumour suppressor genes TP53, p16INK4, p21WAF1, RB1 and the drugs metabolizing enzymes in the development of bone tumours in children

Fundamento. Los genes de supresión tumoral p16ink4, TP53, RB1 y p21waf1 son algunos de los componentes de la compleja red de regulación del ciclo celular y ejercen un control negativo de la proliferación o positivo de la diferenciación en respuesta al daño en el ADN. Se ha investigado la presencia de mutaciones en estos genes y variaciones en la secuencia codificante de las enzimas metabolizadoras de drogas que pudieran estar asociadas con el desarrollo de tumores óseos pediátricos o con el pronóstico de los mismos. Material y métodos. Mediante técnicas de biología molecular basadas en PCR se han analizado las variaciones en la secuencia de los genes p16ink4, TP53, RB1 y p21waf1 y de las enzimas metabolizadoras de drogas en un grupo de 82 osteosarcomas y 47 sarcomas de Ewing así como en una población control de 115 niños sanos. Resultados. Se detectaron mutaciones del gen TP53 en, aproximadamente, 25 por ciento de las muestras en asociación con tumores de mal pronóstico y supervivencia reducida. El gen p16ink4 estaba delecionado un 18 por ciento de los tumores, asociado igualmente a mal pronóstico y supervivencia reducida. El gen p16 estaba delecionado un 18 por ciento de los tumores, asociado igualmente a mal pronóstico y a subtipos histológicos desfavorables, y el gen RB1 presentaba alteraciones en 21 por ciento de los osteosarcomas. No parece existir relación entre la presencia de polimorfismos en las enzimas metabolizadoras de drogas y mutaciones del gen p21waf1 y el desarrollo de los tumores óseos pediátricos. Conclusiones. La alteración de los genes p16ink4, TP53 y RB1 está implicada en el desarrollo del osteosarcoma de Ewing, y parece constituir un factor de mal pronóstico en este tipo de tumores pediátricos. (AU)

[Analysis of the involvement of the tumour suppressor genes TP53, p16INK4, p21WAF1, RB1 and the drugs metabolizing enzymes in the development of bone tumours in children]. / Análisis de la implicación de los genes de supresión tumoral TP53, p16INK4, p21WAF1, RB1 y de las enzimas metabolizadoras de drogas en el desarrollo de tumores óseos en niños.

BACKGROUND: Several tumor suppressor genes such as p16INK4, TP53, RB1 y p21WAF1 are involved in cell cycle regulation in response to DNA damage and belong to the complex pathway that regulates cell proliferation and/or differentiation. We have investigated the presence of mutations in those genes and polymorphisms of Drug Metabolizing Enzymes that could be involved in the development of pediatric bone tumors or in their outcome. MATERIALS AND METHODS: By means of PCR-based techniques, we have analyzed the presence of variations in the coding sequence of p16INK4, TP53, RB1 y p21WAF1 and of the Drug Metabolizing Enzymes in a group of 82 osteosarcomas and 47 Ewing's sarcomas as well as in a control group of 115 healthy children. RESULTS: We detected mutations of the TP53 gene in about 25% of the samples analyzed, most frequently in association with tumors of poor prognosis or reduced survival. The p16INK4 gene was homozygously deleted in 18% of the osteosarcomas, also associated with poor prognosis and unfavourable histologic subtypes; RB1 was altered in 21% of the osteosarcomas. We did not detect relevant associations between polymorphisms of the Drug Metabolizing Enzymes or mutation of the p21WAF1 and development of pediatric bone tumors. CONCLUSIONS: Alteration of TP53, p16INK4 and p21WAF1 seems to be involved in the development of pediatric bone tumors and to be an unfavourable prognostic factor in this type of tumors.

Mite-contaminated foods as a cause of anaphylaxis.

BACKGROUND: Although insect and arthropod contamination of certain foods has been recognized for many years, allergic manifestations caused by ingestion of mite allergens have only rarely been reported. OBJECTIVE: The purpose of this study is to present clinical observations in patients who experienced acute anaphylaxis after eating mite-contaminated foods. METHODS: Thirty atopic subjects who were first seen with systemic anaphylaxis precipitated by the ingestion of wheat-containing foods underwent skin prick tests with inhalant and food extracts, as well as with uncontaminated and mite-contaminated wheat flour. Flour samples were examined microscopically for identification and counting of mites. Der p 1 and Der f 1 levels were quantitated by using immunochemical methods. RESULTS: The most common symptoms were breathlessness, angioedema, wheezing, and rhinorrhea, which started between 10 and 240 minutes after eating. Abundant mites were present in the flour obtained from 28 patients; Suidasia spp. mites were found in grated bread from the other two patients. Positive prick test responses to Dermatophagoides farinae-and mite-contaminated flour and negative skin test responses to wheat extract, other food extracts, and uncontaminated wheat flour were found in all patients. Skin test responses were positive in volunteers with mite allergy even after heating the mite-contaminated flour at 100 degrees C. Screening of 35 unselected flour samples demonstrated the presence of mites in 13 of them (37.1%). CONCLUSIONS: Systemic anaphylaxis can occur after the ingestion of heated or unheated mite-contaminated foods. This problem may be more prevalent in tropical and subtropical countries than previously recognized.