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1.  A Case of Renal Crisis in a Korean Scleroderma Patient with Anti-RNA polymerase I and III Antibodies 
Journal of Korean Medical Science  2006;21(6):1121-1123.
Scleroderma (SSc) renal crisis has been reported to be associated with anti-RNA polymerase I and III (RNAP I/III) antibodies in Caucasians and the Japanese. However, no report is available for Korean SSc patients. Here, we describe the case of a 65-yr-old female SSc patient who developed renal crisis and whose serum contained anti-RNAP I/III antibodies. She was finally diagnosed as having diffuse cutaneous SSc based on skin thickening proximal to the elbows and knees. Sudden hypertension, oliguria, and pulmonary edema were features of her renal crisis. Despite the use of captopril and adequate blood pressure control, her renal function deteriorated. Subsequent renal biopsy findings showed severe fibrinoid necrosis with luminal obliteration in interlobar arteries and arterioles consistent with SSc renal crisis. Serum anti-RNAP I/III antibodies were detected by radioimmunoprecipitation. This is the first report of a renal crisis in a Korean SSc patient with RNAP I/III antibodies.
doi:10.3346/jkms.2006.21.6.1121
PMCID: PMC2721942  PMID: 17179700
Scleroderma, Systemic; Autoantibodies; RNA Polymerase III; RNA Polymerase I
2.  Clinical Features of Polyarteritis Nodosa in Korea 
Journal of Korean Medical Science  2006;21(4):591-595.
Polyarteritis nodosa (PAN) is a systemic vasculitis characterized by multi-organ involvement with protean manifestations. We evaluated the clinical features of PAN in Korea. Twenty-seven patients were diagnosed as PAN at Seoul National University Hospital between January 1990 and July 2003. The male-to-female ratio was 1.7:1 and mean age at onset (±SD) was 47.4±20 yr. Their presenting features at diagnosis were similar to those reported previously, i.e., myalgia, muscle weakness or leg tenderness (70%), fever (52%), weight loss >4 kg (44%), skin rash (44%), peripheral edema (33%), abdominal pain (33%), and arthralgia/arthritis (30%). However, the prevalence of testicular pain or tenderness was higher (24%) than reported previously and only three (11.5%) had HBsAg positivity without liver enzyme elevation. Nine patients (33%) had a five-factor score (FFS) of 2. Fourteen patients (52%) responded to treatment, 2 patients relapsed and 4 died within 1 yr of diagnosis. During a median follow-up of 55.5 months, three of the four PAN-related deaths had an initial FFS of 2. The clinical features of PAN were not significantly different from those reported previously. However, testicular pain or tenderness was more frequent and patients with a high FFS tended to have a poorer prognosis.
doi:10.3346/jkms.2006.21.4.591
PMCID: PMC2729876  PMID: 16891798
Polyarteritis Nodosa; Vasculitis
3.  Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis 
Background/Aims
To investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results.
Methods
A total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records.
Results
The overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 × 10-6). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 × 10-4). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 × 10-5). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 × 10-14), and the κ value was 0.108.
Conclusions
Although several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.
doi:10.3904/kjim.2014.29.3.361
PMCID: PMC4028526  PMID: 24851071
Gout; Uric acid; Synovial fluid; Microscopy, polarization
4.  A Clinical Trial and Extension Study of Infliximab in Korean Patients with Active Rheumatoid Arthritis despite Methotrexate Treatment 
Journal of Korean Medical Science  2013;28(12):1716-1722.
Currently, infliximab is given for disease control for active rheumatoid arthritis (RA) patients despite methotrexate treatment. However, the efficacy and safety of infliximab in Korean patients has not been assessed appropriately. Therefore, we performed placebo-controlled, double-blind, randomized study and extension study. One-hundred forty-three patients with active RA were randomized to receive placebo or infliximab 3 mg/kg intravenously at week 0, 2, 6, 14, and 22 with methotrexate maintenance. Primary endpoint was American College of Rheumatology 20% improvement criteria (ACR20) at 30 week. After the clinical trial, patients on placebo (Group 1) and patients on infliximab who showed ACR20 response (Group 2) were treated with infliximab through another 84 week for evaluation of safety. During clinical trial, patients in infliximab group showed higher ACR20 at week 30 than patients in placebo group (50.1% vs 30.6%, P=0.014). A total of 92 patients participated in the extension study. The maintenance rate of infliximab was 62.0% at 84 weeks of extension study. The overall rate of adverse events was not different between Group 1 and Group 2. In Korean patients with active RA despite methotrexate treatment, infliximab in combination with methotrexate is effective and the long-term treatment with infliximab is well tolerated. (ClinicalTrials.gov No. NCT00202852, NCT00732875)
doi:10.3346/jkms.2013.28.12.1716
PMCID: PMC3857365  PMID: 24339699
Arthritis, Rheumatoid; Infliximab; Placebo-Controlled Clinical Trial; Extension Study; Efficacy; Adverse Event
5.  Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis 
Journal of Korean Medical Science  2013;28(8):1134-1138.
Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 ± 1.83 vs 0.51 ± 1.77, P = 0.038; for sum, -0.50 ± 1.72 vs 1.57 ± 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 ± 0.58 vs 1.06 ± 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 ± 0.93 to -0.14 ± 0.48, P = 0.009; for JSN, 0.47 ± 0.64 to 0.03 ± 0.40, P = 0.032), as was change of sum score (1.09 ± 1.27 to -0.10 ± 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA.
doi:10.3346/jkms.2013.28.8.1134
PMCID: PMC3744699  PMID: 23960438
Arthritis, Rheumatoid; Radiographic Progression; Tofacitinib
6.  Prediction of Microbial Infection of Cultured Cells Using DNA Microarray Gene-Expression Profiles of Host Responses 
Journal of Korean Medical Science  2012;27(10):1129-1136.
Infection by microorganisms may cause fatally erroneous interpretations in the biologic researches based on cell culture. The contamination by microorganism in the cell culture is quite frequent (5% to 35%). However, current approaches to identify the presence of contamination have many limitations such as high cost of time and labor, and difficulty in interpreting the result. In this paper, we propose a model to predict cell infection, using a microarray technique which gives an overview of the whole genome profile. By analysis of 62 microarray expression profiles under various experimental conditions altering cell type, source of infection and collection time, we discovered 5 marker genes, NM_005298, NM_016408, NM_014588, S76389, and NM_001853. In addition, we discovered two of these genes, S76389, and NM_001853, are involved in a Mycolplasma-specific infection process. We also suggest models to predict the source of infection, cell type or time after infection. We implemented a web based prediction tool in microarray data, named Prediction of Microbial Infection (http://www.snubi.org/software/PMI).
doi:10.3346/jkms.2012.27.10.1129
PMCID: PMC3468746  PMID: 23091307
Prediction Model; Microbial Infection; DNA Microarray; Mycoplasma
7.  Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis 
Arthritis Research & Therapy  2012;14(4):R187.
Introduction
Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis.
Methods
FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.
Results
Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14+ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.
Conclusion
These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.
doi:10.1186/ar4018
PMCID: PMC3580583  PMID: 22901757
8.  Serum Elastin-Derived Peptides and Anti-Elastin Antibody in Patients with Systemic Sclerosis 
Journal of Korean Medical Science  2012;27(5):484-488.
The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic sclerosis (SSc) and serum levels of soluble elastin-derived peptide (S-EDP) and anti-elastin antibodies. Serum samples were obtained from 79 patients with SSc and 79 age- and sex-matched healthy controls. Concentrations of serum S-EDP and anti-elastin antibodies were measured by ELISA. The serum concentrations of S-EDP in SSc patients were significantly higher than in healthy controls (median, 144.44 ng/mL vs 79.59 ng/mL, P < 0.001). Serum EDP concentrations were found to be correlated with disease duration in SSc (P = 0.002) and particularly in diffuse cutaneous SSc (P = 0.005). Levels of anti-elastin antibodies were found to be more elevated in SSc patients than in healthy controls (median, 0.222 U vs 0.191 U, P = 0.049), more increased in diffuse cutaneous SSc than limited cutaneous SSc (median, 0.368 U vs 0.204 U, P = 0.031). In addition, levels of anti-elastin antibodies were also found to be negatively associated with presence of anti-centromere antibody (P = 0.023). The S-EDP levels were not found to be correlated with levels of anti-elastin antibodies. The increased S-EDP and anti-elastin antibody levels and association with clinical and laboratory characteristics may reflect the abnormal metabolism in SSc.
doi:10.3346/jkms.2012.27.5.484
PMCID: PMC3342537  PMID: 22563211
Elastin; Elastin-Derived Peptide; Systemic Sclerosis
9.  Association of a functional IRF7 variant with systemic lupus erythematosus 
Arthritis and Rheumatism  2011;63(3):749-754.
Objective
Previous genome wide association study conducted in a population of European ancestry identified rs4963128, a KIAA1542 SNP 23kb telomeric to IRF7, in strong association with SLE. This study was undertaken to investigate whether genetic polymorphism within IRF7 is a risk factor for the development of SLE.
Methods
We genotyped one KIAA1542 SNP rs4963128 and one IRF7 SNP rs1131665 (Q412R) in an Asian population (cases vs. controls: 1302 vs.1479) to assess their association with SLE using custom-designed Beadstation Infinium II platform (Illumina). Subsequently, rs1131665 was further genotyped in independent panels of Chinese (528 vs.527), European American (EA) (446 vs.461) and African American (AA) (159 vs.115) by Taqman genotyping assay to seek confirmation of association in various ethnic groups. Luciferase reporter assay was used to assess the effect of Q412R polymorphism on the activation of IRF7.
Results
Consistent association of rs1131665 (Q412R) with SLE was identified in Asian, EA and AA populations (case vs. control: 2435 vs. 2582; Pmeta = 6.18×10−6, OR = 1.42[1.22–1.65]). Expression of IRF7 412Q risk allele resulted in a 2-fold increase in ISRE transcriptional activity compared with expression of IRF7 412R (P = 0.0003), suggesting IRF7 412Q confers elevated IRF7 activity and may therefore affect downstream IFN pathway.
Conclusion
We showed that the major allele of a nonsynonymous SNP rs1131665 (412Q) in IRF7 confers elevated IRF7 activation and predisposes to the development of SLE in multiple ethnic groups. This result provides direct genetic evidence supporting IRF7 may be a risk gene for human SLE.
doi:10.1002/art.30193
PMCID: PMC3063317  PMID: 21360504
10.  Behçet’s disease presenting with Budd–Chiari syndrome and intracardial thrombus: a case report 
Budd–Chiari syndrome has been described as a late complication of Behçet’s disease. Although the mortality rate associated with Behçet’s disease is low, it can escalate in the presence of Budd–Chiari syndrome and may be further complicated by intracardial thrombus formation. It is therefore important to detect and initiate management early in the disease course. The imaging modalities of choice should be minimally invasive as certain procedures may aggravate Behçet’s disease by initiating a thrombosis or aggravating an existing one. In Behçet’s disease-induced Budd–Chiari syndrome, cardiac investigation is crucial in the work-up in order to identify any cardiac involvement and determine the etiology of intracardial thrombus. Furthermore, the treatment should ultimately focus on controlling the activity of Behçet’s disease. We report an unusual case of Behçet’s disease presenting with Budd–Chiari syndrome complicated by intracardial thrombus in a young Korean man.
doi:10.2147/IMCRJ.S24021
PMCID: PMC3658241  PMID: 23754909
Behçet’s disease; Budd-Chiari syndrome; intracardial thrombus
11.  Salivary chemokine levels in patients with primary Sjögren’s syndrome 
Rheumatology (Oxford, England)  2010;49(9):1747-1752.
Objective. The present study aimed to investigate the salivary chemokine levels in patients with primary SS (pSS) and compare them with those in patients with non-SS sicca symptoms or non-sicca controls.
Methods. Unstimulated and stimulated whole saliva samples were obtained from pSS patients (n = 30) and age- and gender-matched patients with non-SS sicca (n = 30) and non-sicca healthy controls (n = 25). Salivary CCL2, CCL3, CCL4, CXCL8 and CXCL10 levels were measured using a Luminex bead-based multiplex assay.
Results. Patients with pSS had significantly different distributions of salivary CCL3 (P = 0.0001 by the Kruskal–Wallis test), CCL4 (P < 0.00001), CXLC8 (P < 0.0001) and CXCL10 (P < 0.05) levels in unstimulated saliva and all chemokine levels in stimulated saliva when compared with non-SS sicca and non-sicca controls. In comparison with chemokine production rate, the CXCL8 and CXCL10 production rates were significantly higher in pSS than in non-SS sicca controls (P < 0.01 by the Mann–Whitney test). Logistic regression analyses revealed that salivary CXCL8 (P < 0.05) and CXCL10 (P < 0.05) were the significant discriminating chemokines between the pSS and non-SS sicca groups. Although CXCL8 and CXCL10 levels were not correlated with the focus scores, CXCL8 and CXCL10 levels were significantly associated with salivary gland dysfunction.
Conclusion. These results support the notion that CXCL8 or CXCL10 chemokine plays a role in the pathogenesis of pSS.
doi:10.1093/rheumatology/keq121
PMCID: PMC2919196  PMID: 20525739
Sjögren’s syndrome; Sicca; Saliva; Chemokine
12.  Prevalence of Knee Pain and Its Influence on Quality of Life and Physical Function in the Korean Elderly Population: A Community Based Cross-Sectional Study 
Journal of Korean Medical Science  2011;26(9):1140-1146.
To investigate the prevalence of knee pain and its influence on physical function and quality of life (QOL), we examined 504 community residents of Chuncheon, aged ≥ 50 yr. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee anteroposterior radiographs. Self-reported QOL and function were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12 (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The prevalence of knee pain was 46.2% (32.2% in men and 58.0% in women) and increased with age in women. After adjustment of confounders including the presence of knee OA, the subjects with knee pain had significantly worse WOMAC function and SF-12 scores compared to subjects without knee pain. Among the subjects with knee pain, women had worse WOMAC and SF-12 scores than men. Subjects with knee pain had worse physical performance score compared to those without knee pain, especially among females. In conclusion, the prevalence of knee pain is high (32.2% in men and 58.0% in women) in this elderly community population in Korea. Independent of knee OA and other confounding factors, subjects with knee pain have more than 5-fold increase in the risk of belonging to the worst lower extremity function compared to subjects without knee pain.
doi:10.3346/jkms.2011.26.9.1140
PMCID: PMC3172649  PMID: 21935267
Knee Pain; Osteoarthritis; Quality of Life
13.  Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray 
Journal of Korean Medical Science  2011;26(7):851-858.
Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate into multiple connective tissue lineages, which include cartilage, bone, and fat. Cartilage differentiation and chondrocyte maturation are required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. This study was designed to identify novel genes that might help clarify the molecular mechanisms of chondrogenesis. Chondrogenesis was induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in the presence of defined medium for 3, 7, 14 or 21 days. Several genes regulated during chondrogenesis were then identified by reverse transcriptase-polymerase chain reaction (RT-PCR). Using an ABI microarray system, we determined the differential gene expression profiles of differentiated chondrocytes and BM-MSCs. Normalization of this data resulted in the identification of 1,486 differentially expressed genes. To verify gene expression profiles determined by microarray analysis, the expression levels of 10 genes with high fold changes were confirmed by RT-PCR. Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene expression patterns. These findings provide novel information concerning genes involved in the chondrogenesis of human BM-MSCs.
doi:10.3346/jkms.2011.26.7.851
PMCID: PMC3124712  PMID: 21738335
Chondrogenesis; Mesenchymal Stem Cells; cDNA Microarray
14.  Identification of CM1 as a Pathogenic Factor in Inflammatory Diseases and Cancer 
Immune Network  2011;11(3):175-181.
Background
CM1 (centrocyte/-blast marker 1) was defined by a mAb against concanavalin A (Con A) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation.
Methods
However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs.
Results
As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin E2(PGE2). In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation.
Conclusion
CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.
doi:10.4110/in.2011.11.3.175
PMCID: PMC3153670  PMID: 21860611
CM1; ENO1; PGE2; Inflammatory responses; MMP-2/-9
15.  HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis -Genome-wide association study in Koreans with Replication in North Americans 
Arthritis and rheumatism  2009;60(12):3807-3814.
Objective
To investigate the most susceptible genetic loci in systemic sclerosis (SSc) with genome-wide association study (GWAS).
Methods
A genome-wide association study was performed in 137 patients with systemic sclerosis and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine mapping study, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.
Results
The SNPs (rs3128930, rs7763822, rs7764491, rs3117230 and rs3128965) of HLA-DPB1 and –DPB2 on chromosome 6 formed a distinctive peak with log p-values (p =8.16 × 10−13) for association with SSc susceptibility. Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (p = 7.61×10−8) and DPB1*0901 (p = 2.56×10−5)were the most susceptible subtypes for SSc in Koreans. In US Caucasians, two pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (p = 7.58 × 10−17/4.84 × 10−16) or anti-centromere autoantibodies (p = 1.12 × 10−3/3.2 × 10−5), respectively.
Conclusion
Our GWAS in Koreans revealed that the region of HLA-DPB1 and –DPB2 contains the most susceptible loci to Korean SSc. The confirmatory studies in US Caucasians indicated that specific SNPs of the HLA-DPB1 and/or –DPB2 were strongly associated with US Caucasian SSc patients who were positive to anti-topoisomerase I or anti-centromere autoantibodies.
doi:10.1002/art.24982
PMCID: PMC2829245  PMID: 19950302
Systemic sclerosis; Genome wide association study; HLA-DPB1; Anti-topoisomerase I antibody
16.  Tibiofemoral osteoarthritis affects quality of life and function in elderly Koreans, with women more adversely affected than men 
Background
The prevalence of knee osteoarthritis(OA) in East Asia is as common for men and even higher for women than that reported in the Caucasian population. Since both population aging and economic growth have taken place at a much faster pace in Asian countries, such as South Korea, one would expect knee OA to become a major public health problem. However, few studies have examined the influence of knee OA on the quality of life (QoL) and physical function in Asia. The aim of this cross-sectional study is to investigate the influence of knee osteoarthritis (OA) on the quality of life (QoL), function and lower extremity physical performance and the gender difference in its influence in elderly community residents in Korea.
Methods
Participants were from the population-based Hallym Aging Study (HAS). The mean age of the 504 study subjects was 70.2 years and 274 (54%) were women. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee radiographs. Self-reported QoL and function were assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12-item (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The odds ratios(ORs) for belonging to the worst quartile of WOMAC and physical performance test were calculated by logistic regression analysis in radiographic knee OA compared to non-OA after adjustment of confounders. Scores for SF-12 items were analyzed using general linear models and means adjusted for age, BMI and OA severity were compared.
Results
Subjects with radiographic knee OA had significantly increased OR for belonging to the worst WOMAC quartile(for pain, 2.13,95% confidence interval[CI], 1.33-3.40, for stiffness, 2.94,95% CI,1.78-4.86, and for function, 2.97, 95% CI,1.83-4.81) and significantly worse SF-12 scores compared to non-OA after adjustment of age, BMI and sex. Women had worse WOMAC and SF-12 scores compared to men, regardless of the presence of radiographic knee OA after adjustment of age, BMI and OA severity. OA subjects had significantly worse performance score for usual walk and chair stands compared to non-OA subjects, but the ORs were no more significant after adjustment of sex.
Conclusions
Knee OA negatively affects the QoL and physical function in both genders, but women are more adversely affected than men.
doi:10.1186/1471-2474-11-129
PMCID: PMC2898694  PMID: 20569450
17.  The Prevalence of Knee Osteoarthritis in Elderly Community Residents in Korea 
Journal of Korean Medical Science  2010;25(2):293-298.
The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) among community residents and to elucidate the relevant risk factors. This prospective, population-based study was conducted on residents over 50 yr of age in Chuncheon. Subjects completed an interview based on a standardized questionnaire and clinical evaluation including standardized weight bearing semiflexed knee A-P radiographs. We defined a subject with the Kellgren and Lawrence grade ≥2 as having radiographic knee OA (ROA). Symptomatic knee OA (SOA) was defined by the presence of both ROA and knee pain. We obtained symptom information and radiographs from 504 subjects. The prevalence of ROA and SOA was 37.3% and 24.2%, respectively. The prevalence of both ROA and SOA was significantly higher among women than among men. Multivariate analysis revealed that the presence of hypertension, and a manual occupation were significantly associated with the presence of ROA and SOA. Lower level of education was significantly associated with the presence of ROA, and female sex with the presence of SOA. In conclusion, both ROA and SOA are common in the aged adult population of Korea, with preponderance for women.
doi:10.3346/jkms.2010.25.2.293
PMCID: PMC2811300  PMID: 20119586
Osteoarthritis, Knee; Risk Factors; Prevalence
18.  Downregulation of heat shock protein 70 protects rheumatoid arthritis fibroblast-like synoviocytes from nitric oxide-induced apoptosis 
Arthritis Research & Therapy  2009;11(4):R130.
Introduction
Heat shock protein 70 (Hsp70) is a well-known anti-apoptotic protein that blocks multiple steps in the stress-induced apoptotic pathway. Enhanced Hsp70 expression has previously been demonstrated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). The authors investigated the role of Hsp70 in the survival of RA FLSs in a sodium nitroprusside (SNP)-treated environment.
Methods
Targeted knock-down of Hsp70 was performed by RNA interference in RA FLSs at passage 3-7. After SNP treatment, the morphological features of apoptosis were observed by phase-contrast microscopy. Cell survival was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and by flow cytometric analysis after propidium iodide (PI) staining. Bcl-2 expression and signaling pathways (Akt, extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase) were examined with or without Hsp70 downregulation.
Results
Hsp70 downregulation in RA FLSs, induced by small interfering RNA (siRNA), was confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. When treated with SNP, Hsp70 downregulated cells showed markedly less cell blebbing, cytoplasmic condensation, and nuclear shrinkage than non-downregulated control cells. Furthermore, Hsp70 downregulated cells were found to survive better than control cells in MTT assays (mean of absorbance ratio, 4.39 in target cells versus 1.00 in control siRNA-treated cells versus 1.09 in lipofectamine-treated cells, P = 0.001) and according to PI staining results (mean M1 ratio, 0.21 in target cells versus 1.00 in control siRNA-treated cells versus 1.03 in lipofectamine-treated cells, P = 0.001). Bcl-2 expression and Akt phosphorylation were higher in Hsp70 downregulated RA FLSs than in control cells. When cells were treated with LY294002, a potent phosphoinositide 3-kinase inhibitor, Akt phosphorylation and Bcl-2 levels were reduced and Hsp70 downregulation no longer had a cytoprotective effect.
Conclusions
Knock-down of Hsp70 protects RA FLSs from nitric oxide-induced apoptosis by activating the Akt signaling pathway. These results suggest that Hsp70 has a pro-apoptotic role in RA FLSs.
doi:10.1186/ar2797
PMCID: PMC2745814  PMID: 19709444
19.  Beneficial and Adverse Effects of Bosentan Treatment in Korean Patients With Pulmonary Artery Hypertension 
Korean Circulation Journal  2009;39(3):105-110.
Background and Objectives
The purpose of this study was to investigate 1) the beneficial effect of bosentan treatment (125 mg twice daily) on exercise capacity and echocardiographic variables and 2) the profiles and frequency of adverse events in Korean patients with World Health Organization (WHO) class III or IV pulmonary artery hypertension (PAH).
Subjects and Methods
Twelve patients who received bosentan treatment were investigated in an open label manner. One patient was excluded in the final analyses due to a prohibited concomitant medication. A 6-minute walk test and echocardiography were performed at baseline and after 12 weeks of treatment.
Results
The administration of bosentan for 12 weeks resulted in a significant improvement in exercise capacity (measured with the 6-minute walking distance), WHO functional capacity, and in echocardiographic variables. Bosentan treatment was associated with a decrease in the maximal tricuspid regurgitation jet velocity {from 4.7 m/sec (95% confidence interval, 3.89-5.45) at baseline to 4.4 m/sec (95% confidence interval, 3.61-5.1) at 12 weeks, p=0.03} and systolic pulmonary arterial pressure {from 105 mmHg (95% confidence interval, 74.4-135.6) at baseline to 93 mmHg (95% confidence interval, 66.3-120.1) at 12 weeks, p=0.04}. Treatment with bosentan at a dose of 125 mg twice a day was not associated with life-threatening side effects, although a higher incidence of elevated liver enzymes compared to previous studies was noted.
Conclusion
Bosentan at a dose of 125 mg twice daily is considered a clinically optimal, safe dose and can be used as a valuable treatment option in Korean PAH patients with WHO functional capacity III or IV, though close monitoring of liver function is required.
doi:10.4070/kcj.2009.39.3.105
PMCID: PMC2771800  PMID: 19949596
Hypertension, pulmonary; Bosentan; Adverse effects
20.  Hypereosinophilia Presenting as Eosinophilic Vasculitis and Multiple Peripheral Artery Occlusions without Organ Involvement 
Journal of Korean Medical Science  2005;20(4):677-679.
We report here a case with hypereosinophilia and peripheral artery occlusion. A 32-yr-old Korean woman presented to us with lower extremity swelling and pain. Angiography revealed that multiple lower extremity arteries were occlusive. The biopsy specimen showed perivascular and periadnexal dense eosinophilic infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg daily. Her skin lesion and pain were improved and the eosinophil count was dramatically decreased. After discharge, eosinophil count gradually increased again. Cyanosis and pain of her fingers recurred. She had been treated with cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis and tingling sense were progressive. The extremity arterial stenoses were slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum TNF-α was markedly increased. These results suggest that CD40L (a member of TNF-α superfamily) could play a role in the inflammatory processes when eosinophil infiltration and activation are observed. We prescribed prednisolone, cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was discharged.
doi:10.3346/jkms.2005.20.4.677
PMCID: PMC2782169  PMID: 16100465
Hypereosinophilic Syndrome; Vasculitis; Tumor Necrosis Factor-alpha; CD40 Ligand
21.  A Case of Femoral Compressive Neuropathy in AL Amyloidosis 
Journal of Korean Medical Science  2005;20(3):524-527.
We describe a case of a 54-yr-old AL amyloidosis patient who developed femoral compressive neuropathy due to iliopsoas pseudohypertrophy. The patient, who presented with end stage renal disease, was referred to our clinic because of lower extremity weakness and polyarthritis. Finally, he was diagnosed as having kappa-AL amyloidosis, complicated by femoral compressive neuropathy, hypertrophic amyloid myopathy, amyloid arthropathy, carpal tunnel syndrome, and end stage renal disease. Femoral compressive neuropathy has never been reported in association with amyloid induced iliopsoas hypertrophic myopathy. This report expands the clinical spectrum of AL amyloidosis.
doi:10.3346/jkms.2005.20.3.524
PMCID: PMC2782218  PMID: 15953884
Amyloidosis; Muscle Weakness; Femoral Neuropathy
22.  A Case of Hypertrophic Osteoarthropathy Associated with Epithelioid Hemangioendothelioma 
Journal of Korean Medical Science  2004;19(3):484-486.
Epithelioid hemangioendothelioma is a rare vascular tumor, which occurs in the lung, liver, bone, and soft tissue. Hypertrophic osteoarthropathy is a syndrome characterized by subperiosteal new bone formation, joint effusion and clubbing, and may be associated with cyanotic heart disease, chronic pulmonary disease, liver disease, and other miscellaneous diseases. The activation of endothelium and platelets has been suggested to be involved in the development of hypertrophic osteoarthropathy. We report a rare case of hypertrophic osteoarthropathy, which developed in association with hepatic epithelioid hemangioendothelioma with pulmonary metastasis. We also discuss the role of vascular endothelial growth factor in its pathogenesis.
doi:10.3346/jkms.2004.19.3.484
PMCID: PMC2816858  PMID: 15201523
Hemangioendothelioma, Epithelioid; Osteoarthropathy, Secondary Hypertrophic; Vascular Endothelial Growth Factor
23.  Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE). 
Journal of Korean Medical Science  2003;18(4):606-608.
Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.
PMCID: PMC3055077  PMID: 12923344
24.  Phenotype Difference between Familial and Sporadic Ankylosing Spondylitis in Korean Patients 
Journal of Korean Medical Science  2014;29(6):782-787.
Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6±22.2 vs 35.4±34.4, P=0.029) and C-reactive protein (CRP) (1.24±1.7 vs 2.43±3.3, P=0.003) at diagnosis, body mass index (21.9±2.7 vs 23.7±3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.
Graphical Abstract
doi:10.3346/jkms.2014.29.6.782
PMCID: PMC4055810  PMID: 24932078
Spondylitis, Ankylosing; Familial; Sporadic; Phenotype; Recurrence Risk
25.  Cost-of-Illness and Quality of Life in Patients with Ankylosing Spondylitis at a Tertiary Hospital in Korea 
Journal of Korean Medical Science  2014;29(2):190-197.
The objectives of this study were to estimate the cost-of-illness (COI) and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS) in Korea and to evaluate the effects of socio-demographic and clinical factors on the COI and the HRQOL. Face-to-face interview surveys were taken from patients with AS at the Rheumatology Clinic of Seoul National University Hospital. Direct medical and non-medical costs, indirect costs (productivity loss due to job loss and sick leave), and deterioration of HRQOL in patients with AS were measured. Factors associated with COI and HRQOL were analyzed with multiple regression and multivariate logistic regression. A total of 191 patients with AS was enrolled in the study. The COI in patients with AS amounted to 11,646,180 Korean Won (KRW) per patient, and their HRQOL was 0.62. As functional severity worsened, the total costs increased (class I, KRW 7.7 million; class II, KRW 12.9 million; classes III & IV, KRW 25.2 million) and the HRQOL scores decreased (class I, 0.72; class II, 0.61; classes III & IV, 0.24). Functional severity is the major determinant of the COI and HRQOL in patients with AS.
Graphical Abstract
doi:10.3346/jkms.2014.29.2.190
PMCID: PMC3923996  PMID: 24550644
Spondylitis, Ankylosing; Arthritis, Rheumatoid; Cost; Quality of Life

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