• Journal of Acupuncture Research
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• v.21 no.2
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• pp.21-29
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• 2004

목적 : 본 연구는 Interleukin 4 Receptor (IL-4R) 유전자 다형성이 중풍의 발병과 관련이 있는지 알아보기 위해 수행되었다. 대상: 대구한의대학교부속 한방병원에 입원한 중풍환자 56명과 종합건진센터에 내원한 중풍 기왕력이 없는 건강인 83명을 대상으로 하였다. 방법 : 각 그룹에서 개개인마다 DNA를 분리 정제한 후 Taq polymerase로 증폭하여 한천 겔에서 전기영동을 하여 PCR 산물을 확인하였다. PCR 산물은 Pyrosequencing 과정을 통하여 IL4R의 유전형이 자동으로 판정되었다. 결과 : A/A, A/G, G/G의 세가지 유전자형이 검출되었으며 중풍군과 대조군 사이에 유의성 있는 차이가 발견되었다(p=0.005). 그러나 개별 allele 빈도에 있어서는 중풍군과 건강인 사이에 통계적인 유의성이 나타나지 않았다(p=0.995). 결론 : 이상의 결과를 통하여 IL4R 유전자 다형성은 중풍의 발병과는 관련성이 있는 것으로 사려되지만 더 많은 환자를 대상으로 다른 환경요인 또는 유전자와의 연관성에 대한 심도있는 연구가 필요하다고 하겠다.

• Journal of Acupuncture Research
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• v.23 no.1
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• pp.39-51
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• 2006

목적 : 본 연구는 뇌경색에서 일반적으로 많이 사용하는 한방치료가 뇌경색 환자의 단일유전자 염기 다형성에 미치는 영향에 대하여 분석하였다. 2003년 3월부터 2003년 12월까지 경희대학교 한의과대학 부속한방병원 침구과에 입원한 뇌경색 환자 146명과 경희의료원 종합검진센터에 건강검진을 위해 내원한 건강인 192명을 대상으로 하였다. 방법 : 한국인 뇌경색 환자와 건강인에서 혈액을 채취하여 개인마다 DNA를 분리 정제하고 Taq polymerase로 증폭한 후 Pyrosequencing을 통하여 IL4R(interleukin 4 receptor)의 유전형을 관찰하였다. 결과 : 본 연구 결과 IL4R 유전자의 경우 한국인 뇌경색 환자군과 대조군 사이에 유의성 있는 차이가 나타나지 않았다. 결론 : 이상의 결과를 통하여 IL4R 유전자 다형성은 한국인에서 뇌경색의 발병에 관련이 적은 것으로 사려되며 더 많은 환자를 대상으로 다른 환경요인 또는 유전자와의 연관성에 대한 심도 깊은 연구가 필요할 것으로 사려된다.

• 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.

• Journal of Korean Neurosurgical Society
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• v.29 no.6
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• pp.731-737
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• 2000

Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.568-575
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• 2000

Background : Cytokines are chemical mediators that control and modulate many inflammatory processes. They work in different fashions in a variety of diseases. Discriminating between malignant effusion, tuberculous effusion, and parapneumonic effusion are crucial from the clinical view-point in Korea. In the current study, interferon-gamma (IFN-${\gamma}$), soluble interleukin-2 receptor (IL-2R), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured for this purpose. Methods : Pleural fluids from patients with malignant disease, tuberculosis, parapneumonic effusion and lung empysema were collected and gauged using commercial ELISA kits. Results : 34 patients were enrolled in this study. Among these 15 cases were malignant effusions, 12 were tuberculosis pleurisy and 7 were parapneumonic effusion and lung empyema. The levels of cytokines measured in this study were as follows, in order of frequency, malignant effusion, tuberculous effusion, parapneumonic effusion and lung empyema. The levels of INF-${\gamma}$ were higher in tuberculous effusion than in malignant or parapneumonic effusion ($295.5{\pm}585.5$ vs. $16.7{\pm}50$ vs. $10.0{\pm}0$ pg/ml, p>0.05). The levels of IL-2R were higher in tuberculous effusion than in malignant or parapneumoruc effusion ($7423.5{\pm}3752.8$ vs. $3247.4{\pm}1713.3$ vs. $3790.2{\pm}3201.1$ pg/ml, p<0.05). No significant differences were found in the levels of IL-6 between the groups ($600{\pm}12.8$ pg/ml in malignant effusion, $556.4{\pm}161.7$ pg/ml in tuberculous effusion, $514.4{\pm}224.8$ pg/ml in parapneumoruc effusion). IL-10 levels were higher in parapneumoruc effusion than in malignant or tuberculous effusions ($98.4{\pm}141.7$ vs. $28.2{\pm}55.5$ vs. $11.3{\pm}11.7$ pg/ml, p<0.05). Conclusion : These results suggest that the measurement of IL-2R levels in pleural fluids may be a useful means of differentiating between tuberculous effusion and pleural effusions of other origins, and that the measurement of IL-10 levels in pleural fluids may be useful to differentiate between parapneumonic effusion and pleural effusions of other origins.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.464-470
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• 2000

Background : The recognition of bronchial asthma as an inflammatory disease led to the search for soluble markers that would be useful in assessing airway inflammation. Interleukin-6 (IL-6) is a representative proinflammatory cytokine that has been shown to be connected with various inflammatory diseases. IL-6 acts via specific receptors that consist of the IL-6 binding glycoprotein gp80 and the signal transducer gp130. In the search for markers of airway inflammation, delete the role of soluble interleukin-6 receptor (sIL-6R) and IL-6 in acute asthma were investigated. Methods : Serum levels of sIL-6R and IL-6 were measured in 78 acute asthmatics, in 15 patients with asymptomatic asthma and in 10 healthy control subjects by a specific ELISA using a murine antihuman IL-6R, IL-6 mAb ($Quantikine^{(R)}sIL$-6R, IL-6). Results : Serum levels of IL-6 in acute asthmatics significantly exceeded those of control subjects. The levels of sIL-6R in acute asthmatics were also significantly increased compared to those of control subjects. The serum concentrations of IL-6 obtained in acute asthmatics were elevated compared with those in asymptomatic asthmatics. However, association between eosinophilic count/IgE and IL-6/sIL-6R in acute asthma could not be found. Conclusion : Our results suggest that IL-6 may be involved in the pathogenesis of acute asthma, and serum levels of IL-6 and sIL-6R may reflect the severity of airway inflammation.

• Microbiology and Biotechnology Letters
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• v.21 no.2
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• pp.144-149
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• 1993

We have identified a T cell-activating material in the culture supernatant of Streptomyces species. The factor in microbial culture supernatant (MCS) induced thymocyte proliferation in a does dependent fashion and it could be detected by immunoblot analysis using anti-interleukin-1(IL-1) antibody. The factor in MCS was slightly larger(about 21 kd) in its molecular weight than IL-1 on SDS-PAGE. When 125I-MCS was covalently coupled with homo-bifunctional cross-linking agent, disuccinimidyl-propionate to IL-1 receptor(IL-1R) on mouse thymoma cell(EL-4) and immunoprecipitated with anti-IL-1R antibody the molecular weight of this complex of 110 kd was observed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.993-999
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• 2008

Ischemic brain injury such as cerebral infarction is characterized by acute local inflammatory response mediated by cytokines. The mechanism of cytokines involved in cerebral infarction progression are uncompletely revealed yet. We investigated to find out the relationship between single nucleotide polymorphism (SNP) of interleukin 4 receptor(IL4R) and Oriental Medicine therapy efficacy in patients with cerebral infarction for 2 weeks. Oriental Korean Medicine therapies (herbal medicine and acupuncture) were applied daily and motor functions of patients were assessed using the modified cerebral vascular accident (MCVA) scores. Genotyping for IL4R polymorphism was done by pyrosequencing analysis. In IL4R genotypes and the frequency of alleles, there was no significant difference between cerebral infarction patients (n=124) and controls group (n=175). And there was also no significant difference among good and bad responders in cerebral infarction patients. In this study the IL4R genotype might not be the risk factor or a good predictive genetic marker for good and bad responders in cerebral infarction patients in Korean. Further studies including different cytokine genes will be necessary for the exact genetic markers.

• Molecules and Cells
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• v.42 no.12
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• pp.869-883
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• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.135-143
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• 1994

Background: The cell mediated immunity has an important role in the pathogenesis of tuberculosis. sIL-2R has been known as a sensitive marker of T lymphocyte activation Elevated serum levels of sIL-2R have been found in patients with lymphoproliferative disorders, organ transplantation, autoimmune diseases, and various granulomatous diseases. Elevated levels of sIL-2R have been also found in the serum and pleural fluid of the patients with tuberculosis. To evaluate the diagnostic value of sIL-2R in the differentiation of tuberculous pleurisy and nontuberculous pleurisy. We measured the level of sIL-2R in the sera and pleural fluids of 12 patients with tuberculous pleurisy and 32 patients with nontuberculous pleurisy. Method: Samples of pleural fluid and serum were centrifuged at 2500 rpm for 10 min to remove cell pellets. Soluble IL-2R was measured with a sandwitch enzyme immunoassay using the Cellfree(r) Interleukin-2 Receptor Test kit(T-cell science,Inc. Cambridge, MA). Results: The results obtained were as follows: 1) The sIL-2R level in pleural fluid of the patients with tuberculous pleurisy was higher than that of patients with nontuberculous pleurisy(P<0.005). 2) When the sIL-2R level above 5,000 u/ml in pleural fluid was used as the cut-off value to diagnose tuberculous pleurisy, it had a sensitivity of 84.6% and a specificity of 90.9%. 3) The sIL-2R level in the sera of the patients with tuberculous pleurisy was higher than that of patients with bacterial pleural effusions and normal control group(P<0.05) and there was no difference of levels compared with malignant pleural effusions and transudative pleural effusions(P>0.05). 4) In patients with tuberculous pleurisy, the mean concentration of sIL-2R in pleural fluid was higher than that in serum(P<0.005). Conclusion: These findings suggest that the measurement of elevated levels of pleural fluid sIL-2R in tuberculous pleurisy may be useful in the differential diagnosis between patients with tuberculous pleurisy and nontuberculous pleurisy.