Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots

Epidemiological evidence has suggested that some pediatric leukemias may be initiated in utero and, for some pairs of identical twins with concordant leukemia, this possibility has been strongly endorsed by molecular studies of clonality. Direct evidence for a prenatal origin can only be derived by prospective or retrospective detection of leukemia-specific molecular abnormalities in fetal or newborn samples. We report a PCR-based method that has been developed to scrutinize neonatal blood spots (Guthrie cards) for the presence of numerically infrequent leukemic cells at birth in individuals who subsequently developed leukemia. We demonstrate that unique or clonotypic MLL-AF4 genomic fusion sequences are present and detectable in neonatal blood spots from individuals who were diagnosed with acute lymphoblastic leukemia at ages 5 months to 2 years and, therefore, have arisen during fetal hematopoiesis in utero. This result provides unequivocal evidence for a prenatal initiation of acute leukemia in young patients. The method should be applicable to other fusion genes in children with common subtypes of leukemia and will be of value in attempts to unravel the natural history and etiology of this major subtype of pediatric cancer.

Effect of flutamide on survival in patients with pancreatic cancer: results of a prospective, randomised, double blind, placebo controlled trial

Objectives: To assess whether flutamide (Drogenil), a pure androgen receptor blocking agent, improves survival in patients with pancreatic carcinoma and thus whether testosterone is a major growth factor for this tumour.

Dominant-negative p53 mutations selected in yeast hit cancer hot spots.

Clinically important mutant p53 proteins may be tumorigenic through a dominant-negative mechanism or due to a gain-of-function. Examples for both hypotheses have been described; however, it remains unclear to what extent they apply to TP53 mutations in general. Here it is shown that the mutational spectrum of dominant-negative p53 mutants selected in a novel yeast assay correlates tightly with p53 mutations in cancer. Two classes of dominant-negative mutations are described; the more dominant one affects codons that are essential for the stabilization of the DNA-binding surface of the p53 core domain and for the direct interaction of p53 with its DNA binding sites. These results predict that the vast majority of TP53 mutations leading to cancer do so in a dominant-negative fashion.

Valores sociales en los spots publicitarios de bebidas emitidos en España en 2006

El objetivo principal de este artículo es señalar los valores sociales presentes en los spots de bebidas emitidos por televisión, en España, durante el año 2006. Se estudian los valores sociales que transmiten los anuncios al margen de su función comercial. En total, se han analizado 191 spots; para los que se detallan los valores atribuidos al producto y al consumidor. La salud, la juventud, la importancia de las relaciones sociales o de construirse una personalidad genuina son algunos de los principales valores e ideales transmitidos a través de los spots sometidos a estudio.

Observations of Sun Spots, 1739-1743

Eleven-page notebook containing John Winthrop's handwritten observations and calculations. Titled by Winthrop "Observations of 'Spots' on ye Sun with ye Naked Eye," this is the first known record of his scientific observations and records what he saw while examining the sun "with an 8 foot telescope from 6 a.m. til sun set" on the Boston Commons and concluding with "a considerable aurora borealis" that night (April 20, 1739). It has been speculated that his reference to the aurora borealis in these observations may indicate that he recognized the interrelation of the aurora borealis and sun spots, a concept which was not definitively established until the mid-nineteenth century.