bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair.

Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclophosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand beaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks, DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

[Chlamydia pneumoniae infection in children with asthma exacerbation].

Little is known about the significance of C. pneumoniae in wheezing state in children. In this study, a total of 33 children with exacerbation of bronchial asthma were serologically and bacteriologically analyzed to investigate whether C. pneumoniae infection is associated with wheezing in children with bronchial asthma. 1) Of the 33 patients 12 (39%) had an acute antibody rise against C. pneumoniae. C. pneumoniae was isolated from 8 patients (24%) by culture. Based on these findings, 15 cases (45%) were diagnosed as C. pneumoniae infection. 2) There were no significant difference in clinical signs, symptoms and laboratory studies between with and without C. pneumoniae infection. The high incidence of C. pneumoniae infection in children with exacerbation of bronchial asthma suggests its significance as a cause of wheezing. Although there was no specific symptom in C. pneumoniae infection, this infection should be suspected in wheezing children for diagnosis and proper treatment.

TPA-induced arrest of erythroid differentiation is coupled with downregulation of GATA-1 and upregulation of GATA-2 in an erythroid cell line SAM-1.

GATA-1 protein is thought to be a positive regulator of erythroid differentiation. However, ectopic expression of a conditional GATA-2/estrogen receptor chimera was shown to inhibit erythroid differentiation in a hormone-dependent manner, suggesting the negative regulation of erythroid differentiation by GATA-2 protein. Accordingly, we reasoned that the quantitative balance of GATA-1 and GATA-2 protein might affect erythroid differentiation. In this report, we performed specific and quantitative measurements of GATA-1 and GATA-2 protein in a new erythroid cell line, SAM-1, after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). On the basis of these measurements, we show that TPA-induced arrest of erythroid differentiation is coupled with the upregulation of GATA-2 protein, as well as the downregulation of GATA-1 protein. Our results suggest that it is the precise quantitative balance of GATA-1 and GATA-2 protein that regulates erythroid differentiation.