Clinical Entities and Etiology of Invasive Bacterial Infections in Apparently Healthy Children / 소아과

PURPOSE: Invasive bacterial infection is a major cause of morbidity and mortality in children. Previously, we reported etiology of invasive infections in healthy children in 1985-1995. This study was performed to update etiology of invasive bacterial infections in the previously healthy children. METHODS: We reviewed medical records of 98 episodes of invasive bacterial infections in immunocompetent children at the Seoul National University Children's Hospital in 1996-2004. RESULTS: The frequent pathogens identified over all age groups were Streptococcus pneumoniae (33 %) and Staphylococcus aureus (33%). The proportion of Salmonella species and Haemophilus influenzae has been declined to 4% each from 23% and 14%, respectively, compared to previous study. S. agalactiae was the most common isolate in the infants 5 years. Primary bacteremia was the most common clinical diagnosis (27%). S. pneumoniae was responsible for 42% of primary bacteremia, 50% of meningitis, and 69% of bacteremic pneumonia and empyema. S. aureus accounted for 80% of bone and joint infections. The case fatality rate was 8.1% for all invasive infections. CONCLUSION: We reviewed frequency of bacterial agents of invasive infections in children. The data may be useful for pediatricians to select adequate empirical antibiotics in the management of invasive bacterial infections.

Development of Human Antibody Inhibiting RNase H Activity of Polymerase of Hepatitis B Virus Using Phage Display Technique

BACKGROUND: To develop a novel treatment strategy for hepatitis B virus infection, a major cause of liver chirosis and cancer, we aimed to make human monoclonal antibodies inhibiting RNase H activity of P protein playing in important role in HBV replication. In this regard, phage display technology was employed and demonstrated as an efficient cloning method for human monoclonal antibody. So this study analysed the usability of human monoclonal antibody as protein based gene therapy. METHODS: RNase H of HBV was expressed as fusion protein with maltose binding protein and purified with amylose resin column. Single chain Fv (scFv) phage antibody library was constructed by PCR cloning using total RNAs of PBMC from 50 healthy volunteers. Binders to RNase H were selected with BIAcore 2000 from the constructed library, and purified as soluble antibody fragment. The affinity and sequences of selected antibody fragments were analyzed with BIAcore and ABI automatic sequencer, respectively. And finally RNase H activity inhibiting assay was carried out. RESULTS: Recombinant RNase H expressed in E. coli exhibited an proper enzyme activity. Naive library of 4.46 X 10(9) cfu was screened by BIAcore 2000. Two clones, RN41 and RN56, showed affinity of 4.5 X 10(-7) M and 1.9 X 10(-7) M, respectively. But RNase H inhibiting activity of RN41 was higher than that of RN56. CONCLUSION: We cloned human monoclonal antibodies inhibiting RNase H activity of P protein of HBV. These antibodies can be expected to be a good candidate for protein-based antiviral therapy by preventing a replication of HBV if they can be expressed intracellularly in HBV-infected hepatocytes.