RESUMEN
We report findings in a Japanese boy with severe skin rash attributable to biotin deficiency. The patient had an intracranial malformation and developed biotin deficiency due to tube feeding with a single formula for over one year. Results of urinary organic acid analysis were consistent with multiple carboxylase deficiency, and low biotinidase activity was also observed. After biotin supplementation, the skin rash improved and biotinidase activity normalized. We speculate that biotin is one regulating factor in the biosynthesis of biotinidase.
Asunto(s)
Biotina/deficiencia , Biotina/uso terapéutico , Biotinidasa/metabolismo , Biotina/metabolismo , Encéfalo/anomalías , Niño , Preescolar , Suplementos Dietéticos , Eccema/tratamiento farmacológico , Eccema/etiología , Humanos , Discapacidad Intelectual/etiología , Masculino , Cuadriplejía/etiologíaRESUMEN
We screened mutations of two major tumor suppressor genes, p53 and PTEN, in 66 human brain tumors using a yeast-based functional assay and cDNA-based direct sequencing, respectively. The frequency of p53 mutations was 28.8% (19 of 66) and was higher in anaplastic astrocytoma (9 of 14, 64.3%,) than in glioblastoma multiforme (GBM; 7 of 27, 25.9%,), supporting previous speculation that there are at least two genetic pathways leading to GBM, a de novo pathway without p53 mutation and a "progressive" pathway with p53 mutation. PTEN mutation was observed in 8 of 64 tumors (12.5%), mainly GBMs (7 of 26, 26.9%), both with and without p53 mutation. These results suggest that mutation of the PTEN gene is a later event than that of the p53 gene in glioma progression and is associated with both the genetic pathways. All of the detected PTEN missense mutations and an in-frame small deletion inactivated PTEN phosphoinositide phosphatase activity in vitro. Because the tumors containing PTEN mutations also showed loss of heterozygosity in the chromosome 10q23 region flanking the PTEN gene, our data clearly indicate that inactivation of both PTEN alleles occurs in a subset of high-grade gliomas, therefore confirming the previous idea that PTEN acts as a tumor suppressor gene.
Asunto(s)
Neoplasias Encefálicas/genética , Genes p53/genética , Glioma/genética , Mutación , Monoéster Fosfórico Hidrolasas/genética , Proteínas Supresoras de Tumor , Adolescente , Adulto , Anciano , Alelos , Astrocitoma/genética , Niño , Preescolar , Cromosomas Humanos Par 10 , ADN Complementario/metabolismo , Femenino , Eliminación de Gen , Glioblastoma/genética , Humanos , Immunoblotting , Lactante , Fosfatos de Inositol/metabolismo , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Mutación Missense , Fosfohidrolasa PTEN , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The effects of a novel anti-cancer drug, YM 534 on human promyelocytic leukemia line HL-60 cells were investigated. The growth of the cells was completely inhibited with an IC50 of 2.5 X 10(-6) M. The incorporation of 3H-thymidine or 3H-uridine into acid insoluble fraction of the cells was completely inhibited at a 10(-4) M concentration of the drug. However, that of 3H-leucine was suppressed by only 32% at this drug concentration. The single strand scission of DNA of the cells as revealed by alkali sucrose density gradient centrifugation was induced by YM 534 at a 10(-4)M concentration for 60 min. When PM2 DNA in a cell-free system was examined in the presence or absence of reducing agent, no damage to DNA was observed at a 10(-4)M YM 534. The processing of preribosomal to ribosomal RNA of HL-60 cells was retarded at a 10(-5) M level of the drug.