• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.83-88
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• 2005

Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half-life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.982-991
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• 2007

The present study was done to assess the suppressive effects of Haedongpi-san(HDPS), a traditional herbal medicine, on collagen induced arthritis (CIA) in mice and to examined it's effects on immune system. Oral administration of HDPS (200 or 400 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 30 mg/Kg), a positive control. Histological examinations reveled that HDPS inhibited infiltration of inflammatory cells into affected paw joint, and bone erosion and cartilage destruction were greatly reduced compared with control. In paw joint, the number of CD3+ cells and CD11b+/Gr-1+ cells were greatly reduced by HDPS. The levels of pathologic cytokines including TNF-a and IL-6 were significantly decreased in the serum by oral treatment with HDPS. The levels of $IFN-{\gamma}$ in the culture supernatant of splenocyte stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. Rheumatoid factors including IgG, IgM and collagen specific antibody were present much lower in the serum of HDPS treated mice than control. In peripheral blood mononuclear cells of HDPS treated mice, the percentage of CD3+, CD3+/CD69+, CD4+, CD4+/CD25+ cells were significantly decreased, while CD19+ cells were slightly increased compared with control. The absolute number of CD19+, CD3+, CD3+/CD69+, CD4+/CD25+, CD49b+ cell in spleen from HDPS treated mice were significantly decreased. The absolute number of CD3+, CD3+/CD69+, CD4+, CD4+/CD25+ CD8+, CD49b+, CD3+/CD49b+ cells in draining lymph node were significantly increased compared with control. Taken together, HDPS has suppressive effects on rheumatoid arthritis by modulating immune system, and has potential to use as an therapeutic for rheumatoid arthritis.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.2
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• pp.190-199
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• 2003

Purpose: The aim of this study was to find out a clinically appliable method to insert a biodegradable solid material containing holmium-166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after ${\beta}$ -ray irradiation from holmium-166 according to the dose, period and type of tissues. Materials and Methods: 3.0 mCi, 50 ${\mu}l$ of the liquid state $^{166}$Ho-chitosan complex was attached to the absorbable gelatin sponge. The radiation activity measured by dose caliberator was 1.5 mCi. These $^{166}$Ho-chitosan complex containing absorbable gelatin sponges were inserted into the thigh muscles and over the femur bones of the Wistar rats. The cases were evaluated at 2 weeks after insertion, and 4, 6 weeks with respect to the histological changes of the soft tissues and bone, the depth of the tissue necrosis, and the changes of the $^{166}$Ho-chitosan complex containing absorbable gelatin sponges. Results: At 2 weeks, the muscles showed coagulation necrosis, degenerating myocytes, regenerating myocytes, intermuscular edema, and inflammatory cells. The necrosis depth was 3.3 mm. In the bones, there was no osteocyte in the lacuna of cortex (empty lacuna), marrow fibrosis, inflammation. The necrosis depth was 2.9 mm. At 4 weeks, in the muscle, calcification and increased fibrosis with necrosis depth by 3.3 mm were the additional findings. In the bone, marrow fibrosis with necrosis depth by 3.3 mm were detected. At 6 weeks, soft tissue shrinkage, increased fibrosis and granulation tissue formation, and nearly resolving inflammatory reaction were the findings. Conclusion: The local application of the $^{166}$Ho-chitosan complex attached to biodegradable gelatin material with surgery in the laboratory animals resulted in no mortality and morbidity, and satisfactory tissue necrosis. Holmium-166 can be applied to the treatment of the malignant tumor patients.

• Journal of muscle and joint health
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• v.5 no.2
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• pp.238-252
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• 1998

Reumatic arthritis is a disease with joint pain being one of the key symptoms. The patient suffers from the pain, stiff sensation and edema due to the inflammation taking Place In one or more joints. Accompanying these problems are fatigue, unusual exhaustion, fever, tachycardia and weakness. Inaddition, joints are often deformed and muscles shrink along with the progress of edema, coupled with depression and psychological instability resulting from the loss of the mobile function and limitations on the daily life. Some patients become fed up with the long and hard flight with the disease and just give up, which aggravates the symptoms. Others come to the hospital only when the conditions have become serious. We need to prevent these and guide the patients in the right direction. Against this backdrop, this study aims to look into the relations between the knowledge on the part of the patients together with their feeling of self-efficacy and the compliance. The results are expected to help the patients improve their life, In addition to providing useful materials for setting up appropriate plan for nursing intervention. The study was conducted by distributing questionnaire to 88 patients selected from the out-patient department of a university hospital in Inchon, from April 6 to 27, 1998. The following tools were used the yardstick of self-efficacy, developed in 1997 by the Society for the Health of Rheumatism Patients, was used for measuring the levels of knowledge and the feeling of self-efficacy. The degree of compliance was measured by the data collected from documents in addition to the results of the analysis of the interviews with the patients. The reliability of the tools was confirmed. In the analysis, the general characteristics were expressed in figures and percentages. The levels of knowledge, feeling of self-efficacy, and compliance were expressed in the average values and standard deviations. The relations among the variables following the general characteristics were analysed by the t-test and one-way ANOVA. The Pearson correction coefficient was used for the analysis of factors. Multiple-loop analysis was used to identify the variables affecting the compliance. The following are the results of this study. 1. Among the 88 patients, 18 were men and the remaining 70 were women, with a ratio 1 : 3.87. Regarding the age groups, 23 were between 50 and 59 years old, with those between 50 and 69 accounting for 51.1% of the total. High school graduates or higher amounted to 58%. Religious patients was 67% or 59 persons. Fifty nine percent were unemployed, and 58.3% (49 persons) had two children or fewer. The period of suffering from rheumatism varied between 2 months and IS years, with 70% less than years. 2. The average figure In relation to the of knowledge was 17.63 points over 30 or 58. 76%, which means a medium level. 3. The average figure of the feeling of self-efficacy was 60.06 points. 4. The level of compliance was 3.26, which was above average. 5. The relation between the feeling of self-efficacy and compliance showed an "r" value of 0.37, which was significant. It means that the higher the feeling, the greater the compliance points. 6. The analysis of the knowledge level revealed that the difference is found only between the college graduates and junior-high graduates or lower. 7. The feeling of self-efficacy varied along with the age and education level. 8. The general characteristics of patients as discussed above did not show significant difference with the compliance. 9. Regarding the elements influencing the compliance, the number of children, period of suffering, income, age, feering of self-efficacy, knowledge, and compliance had 54% of significance. In conclusion, rheumatism victims can lead a better life if they are appropriately educated, based on efficient training program from the early days of the disease ; if they become able to manage themselves thanks to the training ; and if they are helped by a program focusing on the increase of the feeling of self-efficacy aimed at changing patient's behavior.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.1-7
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• 2003

Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.

• Journal of Acupuncture Research
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• v.21 no.4
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• pp.177-196
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• 2004

Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

• Journal of muscle and joint health
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• v.1 no.1
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• pp.1-30
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• 1994

Rheumatoid arthritis is a chronic systematic disease with unpredictable course of exacerbation and remission, characterized by pain, joint deformity and reduced activity by joint limitation. The growing public awareness of the need for health management of chronic illnesses, provides impetus for nursing to demonstrate social effectiveness by active nursing intervention in this vast area in general, and with rheumatoid condition in particular. However, nursing interventions to date have not demonstrated its active participation in the management of chronic conditions. Nursing intervention for the patients having rheumatoid arthritis is one such area that needs to be studied intensively and to demonstrate their effectiveness empirically. The purposes of this study were two fold : first, to develop a comprehensive program that was intensified with therapeutic joint exercises in water, self-help group activities and utilization of self-efficacy promoting strategies : and secondly, to determine the effect of aquatic exercise program on pain, physiological changes and quality of life in the rheumatoid arthritis patients. Thirty five female subjects participating in this study were selected from outpatients in the Rheumatism Center, Hanyang University hospital. The period of data collection was from December, 1992 to March, 1993 in seoul and Taejeon. Subjects in Taejeon were assigned to the experimental group. The comprehensive aquatic exercise program for the experimental group was carried out three times a week for 6 weeks in regular swimming pool. Subjects in Seoul did not participated in the program, and treated as the control group. Data were analyzed with repeated measure MANCOVA, t-test, ANCOVA, percentage of change, Kruskal-Wallis 1-Way ANOVA using SPSS $PC^+$ program. Results were obtained as follows : 1) Scores on Korean pain scale, Numeric pain score, and RAI score of the experimental group were significantly lower than those of the control group (t=2.11, p=0.022 ; F=4.40, p=0.044 : t=3.10, p=0.002). 2) There was significant improvement in the physiological parameters (higher joint movement parameters, F=15.64, p=0.024 ; higher lean body mass, percentage of change=+12.2, lower body weight, t=1.01, p=0.026 : lower ESR, t=1.69, p=0.001) in the experimental group compaired with subjects In the control group. 3) There was significant improvement in the specific self-efficacy score through the comprehensive aquatic exercise program(t=2.73, p=0.011), but not in the general self- efficacy score(t=0.62, p=0.113). 4) The quality of life failed to show significant improvement in the experimental group as compaired with the control group (F=3.69, p=0.064). 5) In the experimental group, findings from additional analysis showed no significant difference in the specific self-efficacy between those who continued to aquatic exercise after completing 6 week program and those who stopped (X2=0.086, p=0.690). Therefore, adherence to aquatic exercise program for 6 weeks seem to be affected mainly by self-help group activities. An indepth study to delve into articulation of mechanisms affecting the effect of aquatic exercise program be recommended. A further study is necessary to determine the difference in the effect of group and individual aquatic exercise program, to assess factors affecting adherence to exercise for an extended length of time.

• Journal of Life Science
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• v.30 no.11
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• pp.983-989
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• 2020

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.232-240
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• 1997

Background : Postprimary pulmonary tuberculosis is located mainly in upper lobes. The tuberculous lesion involving the lower lobes usually arises from the upper lobe cavity through endobronchial spread. When tuberculosis is confined to the lower lung field, it often masquerades as pneumonia, lung cancer, bronchiectasis, or lung abscess. Thus the correct diagnosis may be sometimes delayed for a long time. Methods : We carried out, retrospectively, a clinical study on 50 patients confirmed with lower lung field tuberculosis who visited the Department of Pulmonary Medicine at Hanyang University Hospital from January 1992 to December 1994. The following results were obtained. Results : Lower lung field tuberculosis without concomitant upper lobe disease occurred in fifty patients representing 6.9% of the total admission with active pulmonary tuberculosis over a period of 3 years. It occurred most frequently in the third decade but age distribution was relatively even. The mean age was 43 years old. Female was more frequently affected than male (male to female ratio 1 : 1.9). The most common symptom was cough(68%), followed by sputum(52%), fever(38%), and chest discomfort(30%). On chest X-ray of the 50patients, consolidation was the most common finding in 52%, followed by solitary nodule(22%) collapse(16%), cavitary lesion(10%), in decreasing order. The disease confined to the right side in 25 cases, left side 20 cases, and both sides 5 cases. Endobronchial tuberculosis (1) Endobronchial involvement was proved by bronchoscopic examination in 20 of 50patients. (2) Mean age was 44years old and female was more affected than man (male to female ratio 1 : 3). Sputum AFB stain and Mycobacterium tuberculosis culture were positive only in 50% of cases unlikely upper lobe tuberculosis, additional diagnostic methods were needed. In our study, bronchoscopic examination and percutaneous fine needle aspiration biopsy increased diagnostic yield by 18% and 32%, respectively. The most common associated condition was diabetes mellitus(18%) and others were anemia, anorexia nervosa, stomach cancer, and systemic steroid usage. Conclusion : When we find a lower lung field lesion, we should suspect tuberculosis if the patient has diabetes mellitus, anemia, systemic steroid usage, malignancy or other immune suppressed states. Because diagnostic yield of sputum AFB smear & Mycobacterium tuberculosis culture was low, additional diagnostic methods such as bronchoscopy and fine needle aspiration biopsy were needed.