• Journal of muscle and joint health
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• v.7 no.1
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• pp.89-101
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• 2000

This study was carried out to compare the bone mineral density and risk factors of osteoporosis between normal and rheumatoid arthritis in postmenopausal women. Sixty-eight postmenopausal patients with rheumatoid arthritis(RA) were compared with 124 postmenopausal normal women. Data were collected from october, 1998 to April, 1999 at Dong-a university hospital in Pusan. From all subjects, individual characteristics such as age, body weight, height, age of menarche, duration of menopause, gravity, parity, and breast feeding period and factors of life style such as milk consumption, exercise, alcohol intake, cigarette smoking, coffee consumption were identified as influencing factors of osteoporosis by questionnaire. From RA patients, health assessment score, Ritchie articular index, erythrocyte sedimentation rate, C-reactive protein and steroid dosage were measured by rheumatologist on measuring bone mineral density. Bone mineral density was measured at the Lumbar spine, femoral neck, femur Ward's triangle, and femur trochanter using dual x-ray absorptiometry. The data was analyzed by using a frequency, t-test, Chi-square, ANCOVA with SPSS PC program. The results could be summarized as follows : 1) There was a significant difference in age and breast feeding period between RA patients and normal women. 2) RA patients took less calcium in the past and practiced less regular exercise in past and present than normal women. 3) There was no difference in lumbar bone mineral density between RA patients and normal women. 4) There was a significant difference in femur Ward's triangle and femur trochanter between RA patients and normal women after adjustment for age and breast feeding period. 5) The prevalence of osteoporosis of all subjects was the highest in femur Ward's triangle. In summary, our findings suggest that the bone mineral densities of femur Ward's triangle and trochanter in postmenopausal women with RA is significantly lower than normal women. Also the exercise participation rate of postmenopausal women with RA is lower than normal women. For the further study, we recommend to develop exercise program that improve the bone mineral density in femur Ward's triangle and trochanter and to test the effect of that exercise program.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.262-266
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• 2010

Tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) is a major proinflammatory cytokine involved in the pathophysiology of juvenile rheumatoid arthritis. Etanercept is an effective inhibitor of $TNF-{\alpha}$ and has shown a beneficial effect in patients with JRA. However, the most important cause of concern related to etanercept administration is infection. We report a case of encephalitis in a JRA patient receiving long-term treatment with etanercept. The patient was a 4-year-old boy with refractory JRA, and he received etanercept subcutaneously at a dose of $0.4\;mg\;kg^{-1}\;day^{-1}$ twice a week for 14 months, along with non-steroidal anti-inflammatory drugs, methotrexate, oral steroids, and sulfasalazine. The patient presented with sudden fever, headache, vomiting, a generalized tonic seizure, and changes in mental status. We suspected a central nervous system infection, and simultaneously administered antibiotics, an antiviral agent, and steroids. After 2 days of hospitalization, his mental function returned to normal, and he showed no further seizure-like movements. Brain magnetic resonance imaging scan of the patient showed a multifocal cortical lesion on both sides of the temporoparietooccipital lobe, which indicated encephalitis. Although we were unable to identify the causative organism of encephalitis, we think that the encephalitis may be attributed to infection, and the use of etanercept may have increased the risk of severe infection. Therefore, etanercept was discontinued and the patient recovered shortly after. To the best of our knowledge, this is the first case of encephalitis in a juvenile rheumatoid arthritis patient treated with etanercept.

• IMMUNE NETWORK
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• v.12 no.1
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• pp.1-7
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• 2012

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24.

• The Journal of Korean Physical Therapy
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• v.14 no.1
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• pp.219-226
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• 2002

Vascular endothelial growth factors(VEGFs) constitute a group of structurally and functionally related growth factor that modulate many important physiological functions of endothelial cells, especially angiogenesis. This paper explain substance, which participate in signaling transduction of VEGF, including Bcl-2, caspase, focal adhesion kinase(FAK), integrin ${\alpha}v{\beta}3$, MAP kinase, nitric oxide(NO)and prostacyclin(PGI2). Physical therapy enhance angiogenesis for repairment of injury which as wound healing, muscle contusion, cerebrovascular disease, rheumatoid arthritis. Therefore this review assist understanding for mechanism of physical therapy as therapeutic angiogenesis.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.120.1-120.1
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• 2003

Nuclear factor-${\kappa}{B}$ (NF-${\kappa}{B}$) belongs to a group of homodimers and heterodimers of Rel/NF-${\kappa}{B}$ proteins that bind to DNA target sites, where they directly regulate gene transcription. The activation of NF-${\kappa}{B}$ has been shown to mediate inflammation and suppress apoptosis. Activated NF-${\kappa}{B}$ has been found n various inflammatory diseases such as rheumatoid arthritis, Atherosclerosis, asthma, nflammatory bowel disease, and Helicobacter pylori-associated gastritis and associated with cancer, cachexia, diabetes, euthyroid sick syndrome, and AIDS. (omitted)

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.132-136
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• 2009

Purpose: WHO(world health organization) announced the FRAX Tool(fracture risk assessment) of new software in the beginning of 2008. FRAX Tool was considered various risk factor, being different from existing fracture risk. In this study, we wanted to know the fracture risk of following the changing of the risk factor of fracture. Materials and Methods: A total of 50 women aged 50~60 were studied. We measured BMD at the part of femur neck which was based on the age, weight, height of individual with GE, Lunar-prodigy. The control group is fracture risk without considering fracture risk factor. The experimental group is previous fracture, parent fracture, current smoking, glucocorticoid, rheumatoid arthritis, secondary osteoporosis, alcohol. if each items makes one 'existence', others are all 'nothing'. and the results produced major osteoporotic region and hip fracture risk in 10-years. Statistics used t-test of SPSS 12.0. Results: The average rate of increment of major osteoporotic region between control group and experimental group, previous fracture-74% increase, parent fracture-96% increase, current smoking-2% increase, glucocorticoid-61% increase, rheumatoid arthritis-29% increase, alcohol-20% increase, secondary osteoporosis-0.18% decrease. The average rate of increment of hip region between control group and experimental group, previous fracture-84% increase, parent fracture-5% increase, current smoking-72% increase, glucocorticoid-84% increase, rheumatoid arthritis-40% increase, alcohol-52% increase, secondary osteoporosis-1.69% decrease. Conclusions: Each fracture risk factor has different rate of increment between major osteoporotic and hip region while in occasion of the second osteoporosis it has little relation because of low P-value. We could know that a contribution of the risk factor is different between major osteoporotic and hip region.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.591-597
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• 2003

Human urokinase kringle domain, sharing homology with angiostatin kringles, has been shown to be an inhibitor of angiogenesis, which can be used for the treatment of cancer, rheumatoid arthritis, psoriasis, and retinopathy. Here, the expression of the kringle domain of urokinase (UK1) as a secreted protein in high levels is reported. UK1 was expressed in the methylotrophic yeast Pichia pastoris GS115 by fusion of the cDNA spanning from Ser47 to Lys135 to the secretion signal sequence of ${\alpha}-factor$ prepro-peptide. In a flask culture, the secreted UK1 reached about 1 g/l level after 120h of methanol induction and was purified to homogeneity by ion-exchange chromatography. Amino-terminal sequencing of the purified UK1 revealed that it was cleaved at the Ste13 signal cleavage site. The molecular mass of UK1 was determined to be 10,297.01 Da. It was also confirmed that the purified UK1 inhibited endothelial cell proliferation stimulated by basic fibroblast growth factor, vascular endothelial growth factor, or epidermal growth factor, in a dose-dependent manner. These results suggest that a P. pastoris sytem can be employed to obtain large amounts of soluble and active UK1.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.125-156
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• 2009

Objectives : To research the trend of studies related to rheumatoid arthritis and to indicate the hereafter direction for its study in oriental medicine and its treatment. Methods : I reviewed 75 domestic oriental medical journals, and 50 medical journals about rheumatoid arthritis published after 2004, and comparative analysis was made. And these theses were classified by college, year, field of study, subject. Results : The following are the results of this study. 1. Classified by oriental medical college, Dae-jeon college published the most theses, followed by Dong-guk, Kyung-hee, Se-myung and Dong-shin college. Han-yang college published the most theses among college of medicine. 2. Classified by type of thesis, experimental theses(70 pieces, 94%) showed higher rate than that of clinical theses(4 pieces, 5%) in oriental medical studies. However, in medical studies, clinical theses(34 pieces, 68%) showed higher rate than that of experimental theses(15 pieces, 30%). 3. Analyzed by subject, the most dealt subject in oriental medicine was herb medication, followed by herbal acupuncture, single herb, electroacupuncture, sasang & gene, acupuncture & moxibustion, complex accordingly. The most dealt subject in medical clinical journals was standards of diagnosis & prognosis, followed by medication, gene analysis, pathogenesis, clinical pattern, operative treatment and complication accordingly. 4. In theses related to herb medication, most of the subject was to evaluate anti-inflammatory and immunoregulatory effects of herb medication with geopungseup, jibitong, hwalhyeolgeoer function. The tendency of experimental methods was focusing on understanding anti-inflammatory and immunoregulatory mechanisms through molecular biologic methods by analyzing cytokine and gene. 5. Most of theses related to herbal acupuncture were experimental studies verifying ant-inflammatory and immnoregulatory effects through methods observing change of cytokine and immunoregulatory factors. Regarding remedies for herbal acupuncture, Ulmus davidiana Planch was most preferred, followed by bee venom. 6. In theses related to single herb, Boik-yak was most prefered, followed by Geopungseup-yak and Hwalhyeolgeoer-yak. Regarding methods of research, there were tendency of shifting from methods verifying travail, anti-inflammatory and anti-pyretic effects through a test of behavior, morphometry, serology and temperature measurement of the rectum and the skin into verifying anti-inflammatory and immunoregulatory effects through observing inflammatory cytokine in the joint and cells of spleen. 7. In theses related to electroacupuncture, ST36 and adjuvant were most preferred as acupoints and induced factor. The tendency of experimental methods was turning from verifying mechanism of travail effect to analyzing inflammation and pain inducing factors. 8. Diverse medical clinical studies were published. Subjects such as diagnosis and prognosis, medication, gene analysis, clinical pattern, operational treatment, complication and pathogenesis were published. Especially, studies about standards of early diagnosis, and research on possible parallel medications with methotrexate were actively inquired. 9. Most of theses related to medical experimental studies was about mediators and receptors related to inflammatory induction and osteoclasia mechanism. Also, it was presented blockage of them can be effective on rheumatoid arthritis. Conclusions : The oriental medicine studies have merit in its diversity of treatment, but it clinical studies is lacking compared to experimental studies. Also, more diversity of subjects is necessary. Therefore, complementary measures are needed. Hereafter, oriental medicine research about rheumatoid arthritis needs more clinical research verifying the effectiveness and safety in clinical field. Also, we require oriental medical standard of diagnosis and researches on pathological generation which would make early checkup and prognosis possible.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.219-240
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• 2009

Since NF-${\kappa}B$ has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of ${\kappa}B$ (NF-${\kappa}B$) in inflammatory signaling for decades. The various molecular components of NF-${\kappa}B$ transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-${\kappa}B$ pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-${\kappa}B$ signaling pathway for many therapeutic applications. However, a gene knock-out study for $IKK{\beta}$ in the NF-${\kappa}B$ pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte $IKK{\beta}$ accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of $IKK{\beta}$ appears to be beneficial to reduce HCC. This article will update issues of the NF-${\kappa}B$ pathway and inhibitors regulating this pathway.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.244-249
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• 2001

The transforming growth $factor-{\beta}$ ($TGF-{\beta}$) is a multifunctional cytokine modulating the onset and course of autoimmune disease as shown in experimental models. In synovial inflammation, there is a potential role for $TGF-{\beta}$ in repairment, the inhibition of cartilage and bone destruction, and the down-regulation of immune response. The biologic effects of $TGF-{\beta}$ depend on the cell type, the isoform and the availability of active $TGF-{\beta}$. We investigated $TGF-{\beta}$ expression in patients with rheumatoid arthritis (RA) and compared to those of osteoarthritis (OA). And we determined a correlation between $TGF-{\beta}1$ and $TGF-{\beta}2$, and also the relationships between each $TGF-{\beta}$ isoform and the parameters for disease activity of RA. Methods: The study population consisted of 20 patients with RA and 20 patients with OA. The commercial ELISA kit was used to study $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in peripheral blood (PB) and synovial fluids (SF). Results: 1) While PB $TGF-{\beta}1$ level was of no difference between RA and OA patient groups, SF $TGF-{\beta}1$ level was higher in RA group than OA group. Similarly, PB $TGF-{\beta}2$ levels of RA and OA groups was not different, but SF $TGF-{\beta}2$ levels was higher in RA group than OA group. 2) In patients with RA, the $TGF-{\beta}1$ levels were higher than $TGF-{\beta}2$ in both the PB and SF, while in patients with OA, there showed higher readings for $TGF-{\beta}1$ than $TGF-{\beta}2$ in SF but no difference between $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in PB. 3) In patients with RA, there were no correlations between PB $TGF-{\beta}1$ and PB $TGF-{\beta}2$ levels, nor between SF $TGF-{\beta}1$ and SF $TGF-{\beta}2$ levels. At the same way, there was no correlation between PB $TGF-{\beta}1$ and SF $TGF-{\beta}1$ levels, nor between each levels of $TGF-{\beta}2$ in patients with RA. 4) There was also no correlation between each $TGF-{\beta}$ isoform and the parameters for disease activity such as ESR, CRP, tender joint count, swollen joint count, rheumatoid factor, and the duration of morning stiffness except between in PB $TGF-{\beta}1$ and disease duration of RA (r=0.637, p<0.01). Conclusion: Each $TGF-{\beta}$ isoforms were higher in synovial fluid of patients with RA than that of patients with OA. The data from the RA patients demonstrated different patterns of expressions of the isoforms depending on which compartment (PB or SF) was investigated. The quantification of different $TGF-{\beta}$ isoform is thought to be important when $TGF-{\beta}$ is measured under disease conditions of RA.