Our data suggest that the HCV core protein promotes cell proliferation through upregulation of the cyclin E expression levels, implying this property of HCV core protein plays an important role in hepatocarcinogenesis.

It has been recognized that the HCV (hepatitis C virus) core protein plays an important role in hepatocarcinogenesis. The functional inactivation of the Rb pathway appears to be a major event for multi-step cancer carcinogenesis. To elucidate the role of the HCV core protein in hepatocarcinogenesis, we investigated the effect of the HCV core protein on the Rb pathway in both Rat-1 cell lines, stably expressing the HCV core protein and the doxycycline-regulated cell lines. The HCV core stable transfectants showed a dramatic decrease in the pRb levels and E2F-1 up-regulation. In the doxycycline-regulated cell lines, the pRb levels were significantly decreased which are followed by E2F-1 up-regulation. HCV core stable transfectants showed higher cell growth rates and were sensitize to apoptosis. Thus, our results first indicate that the HCV core protein decreases the expression of pRb, thereby allowing E2F-1 to be constitutively active, which is thought to result in rapid cell proliferation or sensitizing to apoptosis.

Seventy-seven Acinetobacter isolates were recovered from patients in a Korean hospital during the period from November to December 1998. The isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis for epidemiological relationship, and investigated for antibiotic susceptibility and presence of integrons. Sixty-nine Acinetobacter baumannii isolates were distributed into five groups by RAPD profiles, with 5, 1, 60, 2 and 1 in each group. The major RAPD group of 60 isolates was further divided into six subgroups by antibiograms. Eight isolates belonging to Acinetobacter DNA group 13TU were distributed among six RAPD groups. Seventy-three of the Acinetobacter isolates were resistant to eight or more of the antibiotics tested. Integrase genes were detected in 66 of the 69 A. baumannii (96%) and in 5 of the 8 Acinetobacter DNA group 13TU isolates (63%). The intI1 and intI2 genes were found in 63 and 8 isolates, respectively. The intI3 gene was not detected. All integron-carrying isolates were resistant to multiple antibiotics. All strains isolated from more than one patient carried integrons. According to the results, the presence of integrons was significantly (p<0.01) associated with multiple antibiotic resistance and nosocomial spread in Acinetobacter strains.

Eighty-eight strains of Shigella sonnei isolated in Korea during the period 1980 to 1999 were tested for susceptibility to 13 antimicrobial agents. S. sonnei isolates demonstrated high frequencies of resistance to sulfamethoxazole (97.7%), tetracycline (96.6%), and trimethoprim (95.5%). S. sonnei isolates from the 1990s were more resistant to nalidixic acid than isolates from the 1980s (100 vs 7.7%), while isolates from the 1990s were more susceptible to chloramphenicol than isolates from the 1980s (0 vs 100%). Ampicillin-resistant S. sonnei isolates produced the TEM-1 beta-lactamase with a pI of 5.4. The TEM-1 gene was located on conjugally transferable plasmids in the majority of isolates. S. sonnei isolates were all susceptible to cefotaxime, cefoxitin, ceftazidime, ciprofloxacin, and norfloxacin. These results indicate that cephalosporins and quinolones may be alternative antibiotics for the treatment of S. sonnei infections in Korea.

MDM2 is a substrate of caspase-3 in p53-mediated apoptosis. In addition, MDM2 mediates its own ubiquitination in a RING finger-dependent manner. Thus, we investigated whether MDM2 is degraded through a ubiquitin-dependent proteasome pathway in the absence of p53. When HL-60 cells, p53 null, were treated with etoposide, MDM2 was markedly decreased prior to caspase-3-dependent retinoblastoma tumor suppressor protein (pRb) and poly (ADP- ribose) polymerase (PARP) cleavages. Moreover, down-regulation of MDM2 level was not coupled with its mRNA down-regulation. However, the level of MDM2 was partially restored by proteasome inhibitors such as LLnL and lactacystin, even in the presence of etoposide. Our results suggest that, in the p53 null status, MDM2 protein level is decreased by proteasome-mediated proteolysis prior to caspase-3-dependent PARP and pRb cleavages.