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Summary: Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. Purpose: Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. Methods: We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ − 1.0), osteopenia (− 1.0 > T score > − 2.5), and osteoporosis (T score ≤ − 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < − 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). Results: Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49–0.77)) and spot urine Na/K ratio (1.07 (1.00–1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92–1.41) for osteopenia; 1.43 (1.01–2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. Conclusions: Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma upregulated factor (PAUF) is overproduced in certain types of cancer. However, little is known of the tumorigenic function of PAUF. In this study, we report the X-ray crystal structure of PAUF and reveal that PAUF is a mammalian lectin normally found in plant lectins. We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools. We further confirmed the specificity of the PAUF-TLR2 interaction. PAUF induces extracellular signal-regulated kinase (ERK) phosphorylation and activates the IKK-β-mediated TPL2/MEK/ERK signaling pathway through TLR2. In agreement with the result of TLR2-mediated ERK activation by PAUF, PAUF induces increased expression of the protumorigenic cytokines RANTES and MIF in THP-1 cells. However, PAUF does not fully activate Iκ-B-α signaling pathways in THP-1 cells, and fails to translocate the p65 subunit of the nuclear factor-κB (NF-κB) complex into the nucleus, resulting in no NF-κB activation. Surprisingly, we found that PAUF also associated with the CXC chemokine receptor (CXCR4)-TLR2 complex and inhibited CXCR4-dependent, TLR2-mediated NF-κB activation. Together, these findings suggest that the new cancer-associated ligand, PAUF, may activate TLR-mediated ERK signaling to produce the protumorigenic cytokines, but inhibits TLR-mediated NF-κB signaling, thereby facilitating tumor growth and escape from innate immune surveillance. [ABSTRACT FROM AUTHOR]

Aerosols and source related materials (fly ash from refuse incinerators, vehicle exhaust and soil) were collected in April, 2002 in the northern areas of Jeju-do, Korea, and the Pb isotopic ratios (207Pb/206Pb and 208Pb/206Pb) of the samples were measured in order to estimate the Pb sources of the aerosols. The Pb isotopic ratios of the aerosols were classified into two groups, depending on the sampling date. One group showed similar Pb isotopic ratios with those of the source related materials, suggesting that the contribution of the regional sources to the aerosols was very large. The other showed different Pb isotopic ratios from those of the regional sources and relatively high Pb isotopic ratios compared to the ratios of the first group. The results suggest that in the continental Asia there seems to be a long range transport of Pb with high ratios in desert sands, which are carried by northwest seasonal winds. [ABSTRACT FROM AUTHOR]

To increase the potency of human papillomavirus (HPV) DNA vaccines, we constructed a series of HPV16 L1 vaccines genetically fused with a secretion signal and/or immune cell-recruiting RANTES. The DNA vaccines encoding secretory HPV L1 were constructed by inserting HPV L1 gene into a vector with an ER-targeting secretory signal sequence. The expression plasmid encoding secretory HPV L1 (pER/L1) was fused with cDNA of RANTES, generating pER/L1/R. For comparison, HPV L1 genes were cloned into pVAX1 vector with no signal sequence (pL1), and further linked to the N-terminus (pL1/R) or C-terminus of RANTES (pR/L1). The secretion of L1 proteins was observed in the pER/L1, pER/L1/R, and pR/L1-transfected cells, except the pL1/R-transfected group. Cytoplasmic localization of L1 protein was observed in the cells transfected with pL1/R, but not with pER/L1/R at 48?h after transfection. In mice, RANTES-fused vaccines more effectively elicited the levels of HPV16 L1-specific IgG and IgG2a antibodies than pL1. Of RANTES-fused vaccines, pER/L1/R encoding the secreted fusion protein induced the highest humoral and CD8+ T-cell-stimulating responses. These results suggest that the immunogenicity of HPV L1 DNA vaccines could be enhanced by genetic fusion to a chemokine and secretory signal peptide sequences.Gene Therapy (2003) 10, 1268-1273. doi:10.1038/sj.gt.3301997 [ABSTRACT FROM AUTHOR]

Environmental radiation monitoring in Korea can be categorized as (1) nationwide monitoring program and (2) monitoring program for nuclear facilities. The former is designed to quickly detect any abnormal situation in environmental radioactivity levels. The latter has the objective of evaluating environmental radioactivity levels resulting from the operation of nuclear facilities. This paper describes the two monitoring programs, how they are implemented, items of being measured, analytical techniques, quality control programs and R&D activities associated with the monitoring. Also, some of the latest data obtained by the monitoring programs are introduced. [ABSTRACT FROM AUTHOR]

Although polyethylenimine (PEI) has been widely used as a nonviral vector, there is little mechanistic understanding on PEI-mediated delivery. Here, we studied whether the expression of murine interleukin-2 (mIL-2) plasmids could be improved by complexation with PEI at various N/P ratios, and whether the cellular uptake, nuclear translocation, and retention of plasmids could be affected by the N/P ratios. Compared with the naked mIL-2, PEI/mIL-2 complexes showed at least two orders of magnitude higher expression at Raw264 cells in the N/P ratio-dependent manner. PEI-mediated cellular uptake and nuclear trafficking of plasmids, quantitated by competitive polymerase chain reaction, also depended on the N/P ratios showing the highest cell and nuclear levels of plasmids at 10/1. The higher cellular levels of plasmid DNA after PEI-mediated delivery were also observed in other cell lines. Unlike naked plasmids, PEI/mIL-2 complexes (N/P ratios ≥4/1) showed prolonged cellular and nuclear retention of mIL-2 plasmids. The nuclear translocation and higher cellular level of plasmids given in PEI complexes were similarly observed by fluorescence microscopy. Moreover, PEI/mIL-2 complexes revealed high stability against DNase I, partly explaining the prolonged subcellular retention. These results indicate that the expression of plasmid mIL-2 might be highly enhanced by complexation with PEI and that such increased expression could be attributed by the higher cellular uptake, nuclear translocation and prolonged retention.Gene Therapy 2002 9, 1627–1632. doi:10.1038/sj.gt.3301735 [ABSTRACT FROM AUTHOR]

Polyethylenimine (PEI) has been studied as an efficient nonviral gene transfer vector. Here, we report the biodistribution fates and safety of plasmid DNA intravenously administered in PEI complexes. Using pCMVi3 as a model gene, the biodistribution of plasmid DNA was measured by quantitative polymerase chain reaction. A deletion mutant of pCMVl3 was used as an internal standard. After intravenous administration of PEI/DNA complexes, the serum levels of DNA rapidly declined for up to 15 min. However, after this point, the serum levels of DNA diminished slowly. At 15 min after dose, PEI/DNA complexes showed 33-fold higher distribution of DNA in the lung than did naked DNA. At 24 h, all the organs tested showed much higher levels of plasmid DNA in PEI/DNA complexes, with distribution in the liver and lung being three orders of magnitude higher than naked DNA. The mRNA expression of DNA was observed in various organs of PEI/DNA-treated mice at 12 days after dose. Once a week dosing of PEI/DNA complexes over 3 consecutive weeks did not alter the histology of the organs. However, twice a week dosing over 3 weeks induced a sign of inflammation in the liver. These results indicate that PEI enhances the delivery and retention of plasmid DNA in the organs, especially the liver, but that safe delivery requires proper dosing intervals. [ABSTRACT FROM AUTHOR]