• Genomics & Informatics
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• v.7 no.1
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• pp.20-25
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is characterized by inflammation of the synovial tissue and deterioration of the joint and bone. A recent study reported a potential gene-environment interaction between HLA-DR and smoking. The present study investigated whether a specific gene was related to the association between smoking and the severity of RA (rheumatoid factor levels > 20 IU/ml). We used the resources of the NARAC family collection of GAW 15 databases, and 1139 subjects with RF>20 IU/ml were included in the current analysis. The linkage panel contained 5858 SNP markers, and 5744 SNPs passed quality control criteria. Linear regression analyses, using PLINK software and generalized estimating equation regression models, were used to test for associations between the SNPs and the severity of RA according to smoking groups. Two major findings were established. First, the severity of RA in smokers was associated with rs703618 (p=$6{\times}10^{-5}$), which lies in the intronic region of the stabilin 2 (STAB2) gene on chromosome 12. Second, there were significant differences in the levels of RF between 'ever smokers' and 'never smokers' according to the rs703618 genotype (G/G, A/G, A/A). We investigated whether a specific gene acts as a mediator between smoking and the severity of RA and found that the STAB2 gene could affect this relationship. Our finding indicates that smoking may mediate RA severity by affecting the expression level of a specific gene.

• Imaging Science in Dentistry
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• v.48 no.1
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• pp.1-9
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• 2018

Purpose: To evaluate osseous changes of temporomandibular joint (TMJ) in patients with rheumatoid arthritis (RA) using cone-beam computed tomography (CBCT) and to correlate the imaging findings with the severity of TMJ dysfunction, clinical findings, and laboratory findings. Materials and Methods: This study consisted of 28 subjects, including 14 RA patients and 14 controls, who were scheduled to undergo CBCT imaging for the diagnosis of a complaint not related to or affecting the TMJ. The Fonseca's questionnaire was used to assess the severity of TMJ dysfunction. Rheumatoid factor (RF) and the erythrocyte sedimentation rate (ESR) were assessed in the RA patients. CBCT was then performed in all subjects and osseous TMJ abnormalities were assessed. Results: According to the Fonseca's questionnaire, 14.3% of the patients had no TMJ dysfunction, while 50%, 21.4%, and 14.3% had mild, moderate, and severe dysfunction, respectively. RF was positive in 64.3% of patients, and the ESR level was high in 100%. Imaging findings revealed a statistically significantly higher prevalence of erosion (85.7%), flattening (89.3%), osteophyte formation (32.1%), subchondral cyst (32.1%), sclerosis (64.3%), and condylar irregularities (28.6%) in the RA patients than in the controls. No correlations were found between CBCT findings and the clinical findings, the severity of TMJ dysfunction, disease duration, or laboratory results. Conclusion: RA patients might show extensive osseous abnormalities with no/mild clinical signs or symptoms of TMJ dysfunction that necessitate TMJ imaging for these patients. CBCT is a valuable and efficient modality that can assess osseous TMJ changes in RA patients.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.39-47
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• 2007

Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

• Journal of muscle and joint health
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• v.5 no.2
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• pp.174-190
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• 1998

Osteoporosis has been known as a common complication of rheumatoid arthritis and a major preventable health problem. Lots of studios have demonstrated that changes in life style can help delay or prevent osteoporosis. Therefore nursing intervention related osteoporosis prevention have consisted of education programs aimed at changing dietary and exercise habit. However knowledge gained from education haven't always leaded to behavior change. Therefore it is important to consider other psychological variables in effecting behavior change. Numerous research have found self efficacy and health belief to be an important factor in individual decision making behavior. The purpose of the study was to develop health belief and efficacy expectation promoting program based on Health Belief Model & Self Efficacy Model and to investigate its effects in women with rheumatoid arthritis. For this purpose, one group pretest-post design was used. The subject of the study were 16 women with rheumatoid arthritis in Pusan city and data collection was carried out from April, 1997 to May, 1998. The intervention program was consisted of educating on osteoporosis and enhancing and reinforcing self efficacy by verbal persuasion during the period of 4 weeks. The instruments were used to collect data in this study were Osteoporosis Health Belief Scale, Osteoporosis Self Efficacy Scale, and Osteoporosis Preventive Behavior Scale. Data was analyzed by Wilcoxon signed rank test using SPSS $PC^+$ program. The results are as follows : 1) The behavior should be increased after intervention was supported(Z=-3.5162, p=.0004, diet : Z=-3.2942, p=.0010, exercise). 2) The sub-hypothesis that perceived sensitivity should be increased after intervention was supported (Z=-2.3854, p=.0171). 3) The sub-hypothesis that perceived severity should be increased after intervention was rejected(Z=-1.4327, p=.1520). 4) The sub-hypothesis that perceived benefit should be increased after intervention was supported(Z=-2.6410, p=.0083). 5) The sub-hypothesis that perceived barrier should be decreased after intervention was supported (Z=-2.4138, p=.0158). 6) The sub-hypothesis that efficacy expectation should be increased after intervention was supported(Z=-3.5162, p=.0004). As a conclusion, it was found that health belief and self efficacy promoting program was an effective nursing intervention for preventing osteoporosis of rheumatoid arthritis.

• Bulletin of the Korean Chemical Society
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• v.26 no.11
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• pp.1823-1825
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• 2005

Angiogenesis is tightly regulated by a variety of angiogenic activators and inhibitors. Disruption of the balanced angiogenesis leads to the progress of diseases such as cancer, rheumatoid arthritis, and diabetic blindness. Even though a number of proteins involved in angiogenesis have been identified so far, more protein factors remain to be identified due to complexity of the process. Here I report that pituitary tumor-transforming gene (PTTG) induces migration and tube formation of human umbilical vein endothelial cells (HUVECs). High levels of both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are detected in conditioned medium obtained from cells transfected with PTTG expression plasmid. Taken together, these results suggest that PTTG is an angiogenic factor that induces production of both VEGF and bFGF.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.27-44
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• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.3
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• pp.1-11
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• 2022

Objectives This study was designed to evaluate the healing effect of Cordyceps Militaris (CM) on collagen II-induced arthritis rats. Methods Sprague-Dawley rats were randomly divided into 6 groups (normal, control, positive control, CM with low/medium/high dosage each). Type II collagen mixed with complete Freund's adjuvant (with 1:1 v/v) was injected subcutaneously, and the mixture was injected in a same manner one week after the first injection to boost arthritis. Arthritis index, paw thickness and von Frey test were conducted to observe physical changes. hematoxylin and eosin (H&E) staining was performed to observe knee cartilage. The levels of messenger RNA (mRNA) expressions of interleukin (IL)-1𝛽, IL-6, tumor necrosis factor-alpha (TNF-𝛼) in spleen were assessed by real-time polymerase chain reaction. Results Rheumatoid arthritis is an autoimmune disease that occurs on multiple joints and can lead to temporary shape change of bones or organ failure in severe cases. Here, we aimed to determine the effect of CM extract on rheumatoid arthritis by measuring paw thickness, arthritis index, conducting von Frey test and H&E staining, and evaluating the level of IL-1𝛽, IL-6, TNF-𝛼. As a result, paw thickness, arthritis index significantly decreased in low concentration group, hind leg became less sensitive in all expermental groups. Also, histological analysis showed that the damage of knee cartilage was prevented in all experimental groups. The level of mRNA of IL-1𝛽, IL-6, and TNF-𝛼 in spleen was analyzed to decide the effectiveness of CM extract. IL-1𝛽 did not show significant change, but IL-6 and TNF-𝛼 showed significant decrease in at least one of the experimental groups. Conclusions CM showed protective effect on knee tissue destruction and improved the physical conditions of the leg involving arthritis. Also, it showed that CM has anti-inflammatory effect on specific cytokines inducing rheumatoid arthritis. In conclusion, this study demonstrated that the therapeutic potential of CM for the treatment rheumatoid arthritis, and set the foundation for the further studies.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.103-113
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• 2012

Objectives : The purpose of this study is to evaluate effect of suppressing the expression of cyclo-oxygenase-type-2 (COX-2) as a consequence of inhibition macrophage migration inhibitory factor (MIF) activation by $Sambucus$ $williamsii$ $Hance$ (SWH) pharmacopunctureon rheumatoid arthritis (RA). Methods : In vitro test, synoviocytes extracted from type II collagen-induced arthritis (CIA) mouse's knee joint were cultivated After that, each well of synoviocytes was mixed with the extract of SWH at the dosage of $0.4mg/m{\ell}$, $0.6mg/m{\ell}$, $0.8mg/m{\ell}$, and $1.0mg/m{\ell}$ respectively, and cultivated for 24 hours after the addition. Reverse transcriptase - polymerase chain reaction (RT-PCR) is used to investigate the expression of MIF, Tumor necrosis factor (TNF)-${\alpha}$, COX-2 mRNA. $In$ $vivo$ test, thirty DBA female mice were used, and each ten mice were allocated into three group; normal group, CIA-elicitated group, and group treated with SWH pharmacopuncture on it's the point of $ST_{35}$ after CIA elicitation. It is investigated that change of mice foot thickness, histologic change of sliced synovial joint of mouse, and extent change of MIF, TNF-${\alpha}$, COX-2 in synovial membrane. Results : $In$ $vitro$ test, the expressions of cytokine(MIF, TNF-${\alpha}$, COX-2) mRNAs related to RA were dose-dependent decreased. In the SWH pharmacopuncture group, foot thickness and histologic change of sliced synovial joint were decreased comparing with CIA-elicitated group's change. In the SWH pharmacopuncture group, the suppression of MIF, TNF-${\alpha}$, COX-2 in synovial membrane was clearly shown comparing with CIA-elicitated group's change. Conclusions : It might be suggested that SWH pharmacopuncture mitigate tissue damage originated from rheumatoid arthritis by suppressing the expression of COX-2 as a consequence of inhibition MIF activation.

• Journal of Rheumatic Diseases
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• v.24 no.4
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• pp.227-235
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• 2017

Objective. Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. Methods. Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. Results. Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, $-1.63{\pm}0.30$ vs. n=31, $-2.05{\pm}0.34$) and standard population set analysis (n=31, $-1.51{\pm}0.29$ vs. n=24, $-2.21{\pm}0.34$). Similarly, the change in DAS28 at 12 months did not reach statistical significance ($-1.82{\pm}0.35$ in the rituximab vs. $-2.34{\pm}0.44$ in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). Conclusion. Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.207-219
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• 2004

Objectives : We investigated to find the relationship between single-nucleotide polymorphism (SNP) of IL4R, IL-10 and bee venom therapy efficacy in patients with RA treated with bee venom for 8 weeks. Methods : Korean RA patients (n=114) and healthy subjects (n=109) were included in this prospective study. Korean bee venom was dissolved in saline (diluted 1:3000) and administrated into acupuncture points. Bee venom therapy was applied twice a week and continued for 8 weeks. The clinical response was evaluated using various assessments before and after treatment. Disease severity was measured by determining the number of tender joints and swollen joints. Laboratory studies included ESR, CRP, and rheumatoid factor. Genotyping for IL-4R and IL-10 polymorphism was done by pyrosequencing analysis. Results : 1. In IL4R genotypes, there was significant difference between RA ptitients tind controls group. 2. In IL4R genotypes, there was significant difference among Good, Mild and Bad responders to in RA patients, but in the frequency of alleles and carriers, there were no significant difference. 3. There was no significant difference between RA patients and controls group in IL-10 gene genotypes. 4. In IL-10 genotypes, there was no significant difference among Good, Mild and Bad responders to in RA patients. 5. There was no significant difference in the improvement of ESR, CRP and KHAQ scores after bee venom therapy in RA patients among the IL4R or IL-10 genotypes. Conclusions : In IL-4R genotypes, there was significant difference between RA patients and control group, and among Good, Mild and Bad responders in RA patients. However, in IL-10 genotypes, there was no significant difference between RA patients and controls group and among Good, Mild and Bad responders in RA patients.