No abstract

A novel RNA polymerase I (RPI) driven reporter gene has been used to investigate the in vivo role of the architectural ribosomal transcription factor UBF in gene activation and species specificity. It is shown that the level of UBF overexpression in NIH3T3 cells leads to a proportionate increase in the activities of both reporter and endogenous ribosomal genes. Further, co-expression of UBF antisense RNA suppresses reporter gene expression. Thus, UBF is limiting for ribosomal transcription in vivo and represents a potential endogenous ribosomal gene regulator. In contrast to some in vitro studies, in vivo, the mammalian and Xenopus forms of UBF1 show an equal ability to activate a mouse RPI promoter. This activity is severely impaired in mutants compromised for either dimerization or DNA binding. Similarly, the natural UBF2 splice variant shows a severely impaired capacity to activate RPI transcription. The data strongly suggest that UBF predominantly regulates ribosomal transcription by binding to and activating the ribosomal genes, but does not eliminate a possible secondary role in titrating ribosomal gene repressors such as Rb. Consistent with the DNA folding ability and cellular abundance of the UBF, we suggest that the protein may regulate a structural transition between the potentially active and active chromatin states.

No abstract

Previous studies showed that myocardial Na overload during ischemia directly induced mitochondrial damage. The pathway for Na flux into mitochondria remains unclear. We examined possible routes for Na flux into mitochondria in the ischemic heart. Isolated perfused rat hearts were subjected to 15-to 35-min ischemia followed by 60-min reperfusion and then Na content and respiratory function in mitochondria of the ischemic heart were determined. The mitochondrial Na content of the ischemic heart was ischemic duration-dependently increased, associated with a reduction in mitochondrial respiratory function. To mimic induction of mitochondrial Na overload in vitro, isolated mitochondria were incubated with 6.25 to 50 mM NaCl or sodium lactate, a metabolite of anaerobic glycolysis, in the presence and absence of a mitochondrial Na /Ca 2 exchanger inhibitor CGP37157 and a monocarboxylate transporter (MCT) inhibitor α-cyano-4-hydroxy cinnamic acid (CHCA). Incubation of mitochondria with NaCl or sodium lactate increased the mitochondrial Na concentration. This increase in mitochondrial Na was partially attenuated by the presence of either inhibitor. Combined treatment of mitochondria with both inhibitors attenuated sodium lactate-induced increase in Na content to a greater degree than that treated with either agent. These results suggest that mitochondrial Na /Ca 2 exchanger and MCT inhibitor-sensitive Na transporter are possible pathways for the mitochondrial Na overload in the ischemic myocardium.

Objectives: we analyzed the characteristics of patients with gastric tumors diagnosed with multiple malignant primary neoplasm (MMPN) in the Health District of León. Material and methods: using the information in the Tumor Registry at León Hospital patients selected were those with gastric neoplasms diagnosed between 1993 and 2002. A follow-up was performed until December 31, 2004, and the characteristics of patients diagnosed with a second neoplasm were analyzed. Results: MMPN prevalence was 1,96%; 56% of patients had a history of cancer in first-degree relatives. The most frequent second neoplasms were digestive (26%) and urologic (21%); 87% of patients were diagnosed with a second neoplasm within the first two years. No significative differences in survival were observed among patients with synchronous or metachronous MMPN. Conclusions: MMPN in patients with gastric neoplasms is a relevant problem. While external carcinogenic agents could act as promoters in the development of second neoplasms, these patients seem to have a genetic background favoring the development of MMPN. Secondary prevention is the best measure to avoid MMPN development.