Molecular epidemiology of community-associated antimicrobial-resistant Staphylococcus aureus in Seoul, Korea (2003): pervasiveness of multidrug-resistant SCCmec type II methicillin-resistant S. aureus

There is an extremely high incidence of antimicrobial resistance of the clinical isolates of Staphylococcus aureus in Korea. This study carried out a molecular investigation to determine the prevalence of the community-associated antimicrobial-resistant S. aureus and methicillin-resistant S. aureus (MRSA). The percentage resistance from the nasal swabs of healthy volunteers in 2003 in Seoul is as follows: penicillin (91%), erythromycin (EM, 14%), gentamicin (GM, 9.3%), tetracycline (TE, 8.2%), cephalothin (4%), oxacillin (OX, MRSA; 3.8%), clindamycin (CC, 2.6%), ciprofloxacin (CIP, 0.8%), and sulfamethoxazole/trimethoprim (0.6%). The community-associated MRSA (C-MRSA) strains were examined by pulsed-field gel electrophoresis (PFGE) analysis of the SmaI macro-fragments, multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec (SCCmec) typing using the PCR analysis. The Korean C-MRSA isolates were clustered into three distinct groups. One PFGE group containing the C-MRSA strains showed resistance to CC, EM, and GM, a high level (32-96 microg/ml) of resistance to methicillin, sequence type 5 (ST5), and SCCmec type II, which is the most common hospital associated-MRSA (H-MRSA) isolated in Korea. These results highlight the heterogeneous genetic background of the C-MRSA as well as the pervasiveness of the H-MRSA isolates in this community.     

Identification of origin of unknown derivative chromosomes by array-based comparative genomic hybridization using pre- and postnatal clinical samples

Microarray-based comparative genomic hybridization (array CGH) is a high-resolution and comprehensive method for detecting both genome-wide and chromosome-specific copy-number imbalance. We have developed an array CGH analysis system (consisting of an array CGH chip plus its exclusive analysis software) for constitutional genetic diagnosis and have evaluated the suitability of our system for molecular diagnosis using pre- and postnatal clinical samples. In a blind study, each of the 264 sample karyotypes identified by array CGH analysis was consistent with that identified by traditional karyotype analysis – with one exception, case (47, XXX) – and we were able to identify origins, such as small supernumerary marker chromosomes, which cannot be determined by conventional cytogenetics. We also acquired very accurate, fast and reliable results using a diminutive amount of clinical samples. Taken together, the array CGH platform developed in this study is a rapid, powerful and sensitive technology for pre- and postnatal diagnosis using a very small amount of clinical sample. J. Choe, J.-K. Kang, C.-J. Bae and D.-S. Lee contributed equally to this work.     

Nanoparticulate carrier containing water-insoluble iodinated oil as a multifunctional contrast agent for computed tomography imaging

Contrast-enhanced computed tomography (CT) imaging is a valuable and routine strategy for the clinical diagnosis of various diseases. However, all current CT contrast agents are liquids, so they flow through the blood vessels and disappear very quickly by extravasation. If it were possible to make a blood-compatible particulate contrast agent, we could highlight a particular tissue by either passive or active targeting. In this work, Pluronic F127 and a naturally iodinated compound, Lipiodol, were used to form radiopaque nanoreservoir structures. The resultant nanoparticles have a stable structure at high concentrations, sufficient X-ray absorption, a safety profile similar to or better than that of Iopromide, and a longer circulation time than commercial iodinated preparations. The utility of the resultant radiopaque nanoparticles as a contrast agent was tested using micro-SPECT/CT imaging in vivo. Together with the very good solubility of hydrophobic drugs (e.g., Taxol) in Lipiodol, these results suggest the possibility that these particulate structures and their bioconjugates could become functional CT contrast agents that could deliver therapeutic agents to a particular tissue.     

Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients

Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P < 0.05). Most of the Vietnamese patients with HCC had a high level of HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.     

Analysis of the immune-inducible genes of Plutella xylostella using expressed sequence tags and cDNA microarray

In the present study, the complex gene expression responses of Plutella xylostella to microbial challenges and injury were surveyed using a newly constructed expressed sequence tag (EST) clone collection and cDNA microarray analysis. A total of 1132 P. xylostella ESTs were cloned, annotated and categorized by their putative functions; these included proteases, protease inhibitors, recognition molecules and anti-microbial peptides. GeneOntology revealed that 4% of the P. xylostella ESTs corresponded to immunity-related genes potentially involved in innate immunity. We then used microarray analysis to identify 44 genes that were differentially expressed with at least a two-fold expression difference in P. xylostella before and after pathogen challenge. Together, our EST categorization and microarray profiling analyses allowed us to identify 70 genes that should be considered candidate immune response genes, providing important new insights into the molecular events that occur during the innate immune response in P. xylostella.     

PM10 and pregnancy outcomes: a hospital-based cohort study of pregnant women in Seoul

OBJECTIVE:: The aim of this study was to evaluate the effects of PM10 on birth outcomes using a prospective cohort of pregnant women. METHODS:: The multicenter prospective study was conducted in Korea from 2001 to 2004. To estimate the effects of PM10 exposure on birth outcomes, the logistic and linear regression model and the generalized additive model for nonlinear relationships were used. RESULTS:: Stillbirths were affected by PM10 level during the third trimesters (OR = 1.10, 95% CI = 1.02-1.14), and birth defects were influenced by the PM10 exposure during the second trimesters (OR = 1.16, 95% CI = 1.00-1.34). Intrauterine growth retardation was affected by the first trimester's PM10 exposure. On the other hand, premature birth was affected by the PM10 exposure during the third trimester, and low-birth-weight births were affected by the PM10 level during entire trimesters of pregnancy. CONCLUSIONS:: PM10 exposure during pregnancy may result in adverse birth outcomes with different critical periods.     

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema

PurposeSentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm.MethodsProspectively collected medical records of 910 patients were reviewed. Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic.ResultsTogether with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs. breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111).ConclusionThe risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.     

Synthesis and cytotoxicity evaluation of substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzofluorene-5,6-diones

The substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzo[a]fluorene-5,6-diones were synthesized from 6,7-dichlorophthalazine-5,8-dione and 6,7-dichloroquinoline-5,8-dione, respectively. The cytotoxic activities of the prepared compounds were evaluated by an SRB (Sulforhodamine B) assay against the following human cancer cell lines: A549 (lung), SK-OV-3 (ovarian), SK-MEL-2 (melanoma), XF 498 (CNS), and HCT 15 (colon). Almost all synthesized pyridazino[4,5-b]phenazine-5,12-diones (7a-j) presented higher cytotoxicity than that of doxorubicin (IC(50)=0.097-0.225 microM) against the cancer cell lines. In particular, the cytotoxicity of compounds 7f (R(1)=Et) and 7h (R(1), R(2)=Me) against all human cancer cell lines examined was about 10 times higher than that of doxorubicin. However, the cytotoxicities of several synthesized azabenzo[a]fluorene-5,6-diones (12a, 12c, 12d, 12e, and 12g) against the cancer cell lines in vitro were comparable to those of doxorubicin.