Seong Jae Choi

The Prevalence of Metabolic Syndrome in Patients with Gout: A Multicenter Study

It has been suggested that hyperuricemia and possibly gout are associated with the metabolic syndrome, but there have been no direct studies. This study was undertaken to obtain the prevalence of the metabolic syndrome in patients with gout and to compare it with those from the general population studies. This was a 4-institutional case-historical control study composed of 168 patients with gout. We assessed the prevalence of metabolic syndrome according to the ATP III criteria and compared the prevalence with that of the historical controls. To elucidate the factors in gout that were associated with metabolic syndrome, a multivariate analysis was done. The age-adjusted prevalence of metabolic syndrome in gout patients was 43.6%, which was significantly higher than that of the Korean control population (5.2%) from the previous studies. Patients with gout had more components of metabolic syndrome than did the controls. Body mass index (BMI, OR=1.357 (95%CI 1.111-1.657)) and high density lipoprotein (HDL, OR=0.774 (95%CI 0.705-0.850)) were the variables most significantly associated with the occurrence of metabolic syndrome in gout, but alcohol consumption did not show such associations. Gout is associated with the metabolic syndrome, and furthermore, obesity and dyslipidemia were the factors most associated with the syndrome in these patients.

Prostaglandin E2 augments IL-10 signaling and function.

In inflamed joints of rheumatoid arthritis, PGE2 is highly expressed, and IL-10 and IL-6 are also abundant. PGE2 is a well-known activator of the cAMP signaling pathway, and there is functional cross-talk between cAMP signaling and the Jak-STAT signaling pathway. In this study, we evaluated the modulating effect of PGE2 on STAT signaling and its biological function induced by IL-10 and IL-6, and elucidated its mechanism in THP-1 cells. STAT phosphorylation was determined by Western blot, and gene expression was analyzed using real-time PCR. Pretreatment with PGE2 significantly augmented IL-10-induced STAT3 and STAT1 phosphorylation, as well as suppressors of cytokine signaling 3 (SOCS3) and IL-1R antagonist gene expression. In contrast, PGE2 suppressed IL-6-induced phosphorylation of STAT3 and STAT1. These PGE2-induced modulating effects were largely reversed by actinomycin D. Pretreatment with dibutyryl cAMP augmented IL-10-induced, but did not change IL-6-induced STAT3 phosphorylation. Misoprostol, an EP2/3/4 agonist, and butaprost, an EP2 agonist, augmented IL-10-induced STAT3 phosphorylation and SOCS3 gene expression, but sulprostone, an EP1/3 agonist, had no effect. H89, a protein kinase A inhibitor, and LY294002, a PI3K inhibitor, diminished PGE2-mediated augmentation of IL-10-induced STAT3 phosphorylation. In this study, we found that PGE2 selectively regulates cytokine signaling via increased intracellular cAMP levels and de novo gene expression, and these modulating effects may be mediated through EP2 or EP4 receptors. PGE2 may modulate immune responses by alteration of cytokine signaling in THP-1 cells.

Pd-nanocrystal-based nonvolatile memory structures with asymmetric SiO2∕HfO2 tunnel barrier

Pd nanocrystals (NCs) on asymmetric tunnel barrier (ATB) composed of stacked SiO2 and HfO2 layers have been employed for nonvolatile memory devices. The Pd-NC layers are formed by electrostatic self-assembly of negatively charged colloidal Pd NCs. The presence of isolated Pd NCs of ∼5nm embedded in HfO2 is confirmed by scanning and transmission electron microscopy images. Outstanding program∕erase (P∕E) properties from C‐V curves are observed with a memory window of 6V under ±17V. Extrapolation of the data up to ten years shows that the flatband voltage drops at the P∕E levels are maintained within only 1.0∕0.5V, respectively, resulting from the efficient data retention based on the ATB. These results are promising enough for the memory structure to be utilized for the multilevel charge storage.

Meta-analysis of genome-wide linkage studies for bone mineral density

AbstractGenome-wide linkage studies have shown several chromosome loci that may harbor genes that regulate bone mineral density (BMD), but results have been inconsistent. A meta-analysis was performed to assess evidence for linkage of BMD across whole genome scan studies. Eleven whole-genome scans of BMD or osteoporosis containing 3,097 families with 12,685 individuals were included in this genome scan meta-analysis (GSMA). For each study, 120 genomic bins of ∼30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. A total of seven bins lie above the 95% confidence level (P=0.05) and one bin was above the 99% confidence level (P=0.01) in the GSMA of eleven linkage studies: bins 16.1 (16pter-16p12.3, Psumrnk <0.01), 3.3 (3p22.2-3p14.1), 1.1 (1pter-1p36.22), 18.2 (18p11.23-18q12.2), 6.3 (6p21.1-6q15), 20.1 (20pter-20p12.3), and 18.1 (18pter-18p11.23). GSMA was performed with seven studies with linkage scores of LOD >1-1.85 for sensitivity test, confirming the linkage on chromosome 16p and 3p and revealing evidence of new linkage in bins 10.2 (10p14-10q11.21) and 22.2 (22q12.3-22pter). In conclusion, the meta-analysis of whole-genome linkage studies of BMD has shown chromosome 16pter-16p12.3 to have the greatest evidence of linkage as well as revealing evidence of linkage in chromosomes 1p, 3p, 6, 10, 18, 20p, and 22q across studies. This data may provide a basis with which to carry out targeted linkage and candidate gene studies particularly in these regions.

Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis

STAT4 is a transcription factor that has been implicated in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recently, several reports has documented that a STAT4 haplotype is associated with RA, SLE and Sjogren’s syndrome. To summarize and review these findings, we conducted a meta-analysis of all relevant reports published before September 2008. Studies on STAT4 rs7574865 single nucleotide polymorphism (SNP) of RA and SLE were identified using PubMed. Meta-analyses were performed for 15,609 patients with RA and 15,793 controls from 14 published studies and for 2,478 patients with SLE and 5,058 controls from 8 published studies. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on random effects models were calculated for all available studies. The overall ORs for the minor T allele of STAT4 rs7574865 SNP were 1.27 (95% CI 1.20–1.34) in RA and 1.57 (95% CI 1.44–1.71) in SLE. Asian controls have significantly higher allele frequency (32%) for the minor T allele of STAT4 rs7574865 SNP than population of European origin (22%), however, there was no significant difference of ORs for RA and SLE by ethnicity. No apparent effect of anti-CCP positivity was found in stratified analysis. The risk of STAT4 genotype for SLE was significantly higher than for RA in populations of European origin and Asian. The results of our meta-analysis demonstrated that STAT4 rs7574865 SNP is significantly associated with RA and SLE. In addition to specific alleles of HLA-DRB1, the minor T allele of STAT4 rs7574865 SNP is a common RA risk factor in populations of European origin and Asian.

Scleroderma associated with ANCA-associated vasculitis

Scleroderma and ANCA-associated vasculitides (AAV), such as microscopic polyangiitis, are distinct disease entities, but are rarely known to coexist with each other. We have reported on two cases of scleroderma patients for the first time in Korea, and these patients were initially known to have only limited type scleroderma with pulmonary fibrosis, but eventually they were found to be ANCA-positive with the associated clinical features of vasculitis. Both were treated with high-dose steroids and cyclophosphamide and remitted without major sequelae. When scleroderma patients exhibit atypical features such as normotensive renal failure with signs of active inflammation, the possibility of AAV should always be considered.

Ankylosing spondylitis susceptibility loci defined by genome-search meta-analysis

AbstractIn genome scans of ankylosing spondylitis (AS), with the exception of the HLA loci, linkage has not been easy to replicate across studies. We applied the genome-search meta-analysis (GSMA) method to genome scans of AS and spondyloarthropathy (SpA) to assess evidence for linkage across studies. Three AS genome scans and one SpA scan including 430 families with 1,048 affected individuals were used. All four original genome scans mainly analyzed Caucasian families. Seven bins had both Psumrnk and Pord <0.05, suggesting these bins most likely contain AS-linked loci; bin 6.2, 6.1, 6.3, 16.3, 19.2, 17.1, and 16.4. The GSMA produced significant genome-wide evidence for linkage on chromosome 6p22.3-6p21.1 (Psumrnk=0.000003), including the HLA locus. In addition to the HLA-B27 locus, strong linkage evidence was found on chromosome 6p25.3-6p22.3 (Psumrnk=0.0013) and 6p21.1-6p15 (Psumrnk=0.043). In the GSMA of four genome scans including one SpA study, the bin 9.4 (9q21.32-9q33.1) was newly found for linkage (Psumrnk=0.043, Pord=0.013). This GSMA added the evidence of the HLA loci as the greatest susceptibility factor to AS and showed evidences of chromosome 6, 16q, 19, 17p, and 9q as non-HLA susceptibility loci.

Selective Oxidation on Metallic Carbon Nanotubes by Halogen Oxoanions

Chlorine oxoanions with the chlorine atom at different oxidation states were introduced in an attempt to systematically tailor the electronic structures of single-walled carbon nanotubes (SWCNTs). The degree of selective oxidation was controlled systematically by the different oxidation state of the chlorine oxoanion. Selective suppression of the metallic SWCNTs with a minimal effect on the semiconducting SWCNTs was observed at a high oxidation state. The adsorption behavior and charge transfer at a low oxidation state were in contrast to that observed at a high oxidation state. Density functional calculations demonstrated the chemisorption of chloro oxoanions at the low oxidation state and their physisorption at high oxidation states. These results concurred with the experimental observations from X-ray photoelectron spectroscopy. The sheet resistance of the SWCNT film decreased significantly at high oxidation states, which was explained in terms of a p-doping phenomenon that is controlled by the oxidation state.

Vitamin D receptor TaqI, BsmI and ApaI polymorphisms and osteoarthritis susceptibility: A meta-analysis

OBJECTIVE Genetic factors may play a role in the development of osteoarthritis (OA), and vitamin D receptor (VDR) polymorphisms have been associated with several common diseases including OA by some studies. The aim of this study was to explore whether the VDR polymorphisms confer susceptibility to OA. METHODS We conducted meta-analyses on the associations between the VDR TaqI, BsmI, ApaI polymorphisms and OA using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) contrast of homozygotes, using fixed and random effects models. RESULTS A total of 10 relevant studies on VDR polymorphisms and OA were included in this meta-analysis, which involved in total 1591 OA patients and 1781 controls. Nine studies were performed on VDR TaqI polymorphisms, 6 on VDR BsmI polymorphisms, 5 on VDR ApaI polymorphisms. Accordingly, to our meta-analysis of VDR TaqI polymorphisms, no association was found between OA and the VDR TaqI T allele among in all study subjects (OR=0.841, 95% CI=0.663-1.067, p=0.155). Stratification by ethnicity yielded no association between the VDR TaqI T allele and OA in Europeans or Asians. Moreover, no association was found between OA and the VDR TaqI polymorphisms by the meta-analyses of recessive and dominant models, and contrast of homozygotes. No association was found between OA and the VDR polymorphisms with respect to the BsmI and ApaI polymorphisms by meta-analyses. CONCLUSIONS No association was found between the VDR TaqI, BsmI, or ApaI polymorphisms and OA susceptibility by this meta-analysis, which included 3372 subjects.

Osteoarthritis susceptibility loci defined by genome scan meta-analysis

Genome scans for osteoarthritis (OA) have yielded inconsistent results. The absence of replication of linkage might be due to the lack of power of individual studies. A meta-analysis of published data was performed to assess evidence for linkage of OA across genome scan studies. Three OA whole-genome scans including 893 families with 3,000 affected individuals were used for genome scan meta-analysis (GSMA). A total of five bins lie above 95% confidence level (P=0.05) and one bin is above 99% confidence level (P=0.01) in OA GSMA; bins 7.6 (7q34–7q36.3, Psumrnk =0.0035), 11.3 (11p12–11q13.4), 6.3 (6p21.1–6q15), 2.8 (2q31.1–2q34) and 15.3 (15q21.3–15q26.1). The highest summed bin was bins 7.6. In conclusion, the OA GSMA has shown that chromosome 7q34–7q36.3 have the highest summed rank and four additional loci with significant summed ranks across studies.