류마치스성 질환의 면역학적 진단

김신규 ( Think You Kim ) 대한결핵 및 호흡기학회 1988 Tuberculosis and Respiratory Diseases Vol.35 No.3

Internal Impact Score를 이용한 대한류마티스학회지 게재 논문의 자체 기여도 조사

김덕언 ( Duck An Kim ),김신규 ( Think You Kim ) 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.3

Objective: The authors created a new citation index of the Journal of the Korean Rheumatism Association (JKRA) and, based on the index, developed internal impact score, which can measure contribution to the development of the journal by manuscript, by author and by institute. Thus, we report the results in this paper. Methods: For manuscripts published in the JKRA from Volume 1 No. 1 in 1994 to Volume 13 No. 4 in 2006, we built a database of the journals and their references, and created an index using the database. The citation index were analyzed using three indicators internal impact score for manuscript (IIS-M), internal impact score for author (IIS-A) and internal impact score for institute (IIS-I). Results: The total number of references cited in the manuscripts was 7,341, and of the references, 80 (1.1%) had been published in the JKRA. The mean IIS-M of all the cited manuscripts was 0.46. The total number of authors participated in the cited manuscripts was 226. In IIS-A calculated in consideration of each author`s participation and the weight of manuscripts, the highest score was 19.253. The number of institutes that had produced the cited manuscripts was 29. In IIS-I calculated in consideration of each organization`s participation and the weight of manuscripts, the highest score was 92. Conclusion: If the indicators developed by the authors are used as tools for analyzing the citation indexes of journals, they can quantify the contribution of manuscripts, authors and institutes to each journal, and compensation based on the quantified contribution will promote the development of academic journals considerably.

ANCA 검사의 임상적 유용성에 관한 재평가

전래희 ( La He Jearn ),김신규 ( Think You Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.1

Objective: Antineutrophil cytoplasmic antibody (ANCA) is known to be associated with vasculitides. But recently ANCA has been reported in some chronic inflammatory diseases regardless of vasculitic condition. Although the incidence of vasculitis was low in Korea, we occasionally encounter patients with positive ANCA. And it was doubtful whether ANCA positivity of reports, in time that ANCA test was introduced in Korea, was true. So this study aimed to reevaluate the clinical utility of ANCA with the modern stabilized substrate. Methods: 162 patients with positive ANCA from Jan. 2002 to Jan. 2003 were investigated. ANCA was tested by indirect immunofluorescence assay using ALCA kit (ImmunoThink(R), Korea). Results: Of 162 patients, 158 were P-ANCA positive, 2 were C-ANCA positive and 2 were atypical C-ANCA positive. Most of the ANCA positive patients had chronic inflammatory diseases-129 patients (79.6%) with rheumatoid arthritis (RA), 4 (2.5%) with lupus and 4 (2.5%) with ulcerative colitis. Only 3 patients (1.9%) had vasculitides and the remaining seventeen patients had other diseases. Among the RA patients with ANCA, 27.9% were seronegative RA. Conclusion: In order to increase the clinical applicability of ANCA test in diagnosing vasculitides, it is essential to decrease the false positivity by using stabilized substrate and by adapting professional interpretation from experts. And our results suggest that ANCA test can be useful for diagnosing chronic inflammatory diseases such as rheumatic diseases (especially RA) along with vasculitides in Korea. Further study will be needed for the diagnostic utility of ANCA in RA.

항응고제에 따른 HLA-B27 검사를 위한 세포 생존능 보존 기간의 비교

김홍석 ( Hong Seok Kim ),전래희 ( La He Jearn ),김신규 ( Think You Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.3

Objective: HLA-B27 test require at least 80% of viable cells. So the procedures require immediate processing of the blood samples. To increase the efficiency and the cost-effectiveness of the laboratory, longer maintenance of cell viability is requested. For this purpose, we compared the cell viability of blood samples collected in heparin tubes with those collected in ACD tubes. Our aim was to determine whether the length of storage that could maintain adequate cell viability for HLA-B27 testing depends on the anticoagulants in the storage tube and to ascertain the qualified HLA-B27 results after several days of storage. Methods: We collected 15 blood samples in ACD and heparin tubes. The samples were stored at 4℃ for 6 days and after which, 2 mL of the sample was used to confirm the viability of lymphocytes every 24 hours for 5 days. For evaluating the reproducibility, the HLA-B27 test was performed at the day of sampling and after 6 days of refrigeration. Results: There was no difference in cell viability between ACD and heparin until the sixth day, but a statistically difference was observed from the seventh day (p=0.004). The HLA-B27 test showed no different results even after 6 days of storage. Conclusion: We suggest that the heparin tubes have a same storage benefit as the ACD tubes of blood for HLA-B27 testing for less than a week. This can affect more economic and efficient laboratory management for HLA-B27 testing.

다약제 내성 유전자를 이용한 항류마티스 약제의 내성 검사 방법 개발

김상경 ( Sang Gyung Kim ),서헌석 ( Hun Suk Suh ),최정윤 ( Jung Yoon Choe ),이종원 ( Jong Won Lee ),서장수 ( Jang Soo Suh ),김신규 ( Think You Kim ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.1

Objective: A number of disease-modifying anti-rheumatic drugs (DMARDs) have been shown to be more effective than placebo in the management of rheumatoid arthritis (RA). However, most course of DMARDs, except methotrexate, are discontinued after 2 or 3 years, because of toxicity, lack of efficacy or escape from control. The multi-drug resistance (MDR) is a phenomenon in which cells develop cross-resistance to many agents such as anthracyclin, vinca alkaloids and colchicine. In our hypothesis, MDR phenomenon could be implicated in acquired resistance to DMARDs in RA. We have established a mdr1 cell line and tested whether DMARDs are substrate for P-glycoprotein (P-gp). Methods: The mdr1-cDNA was cloned into retroviral vector, and the recombinant retroviral vector was transfected into PA317 cells. The target cells, NIH3T3, were infected with recombinant retroviruses. A colony most resistant to vinblastin was selected for the following experiments; expression of mdr1 gene in NIH3T3 cells was confirmed by RT-PCR, and biological function of mdr1 gene product, P-gp, was tested using Rhodamine-123 (Rh123) efflux assay. Resistance of the target cells expression P-gp which can survive against hydroxychloroquine (HCQ) and methotrxate (MTX) were measured by MTT assay. Results: RT-PCR for mdr1 gene showed successful transfer of the gene into the NIH3T3 cells. Rh123 assay revealed expression of P-gp on the selected cells as follows; Rh123 efflux activity of uninfected NIH3T3 cells was 6%, that of PLXSN was 0.2%, and that of selected cells was 44%. The 50% proliferation inhibitory capacity of the selected cells were twice for HCQ but there was no difference of that for MTX. Conclusion: We established a mdr1 cell line and using the cell line, HCQ was a substrate of MDR, but MTX was not related to MDR.

대한류마티스학회지에 사용된 통계기법의 평가

박일규 ( Ile Kyu Park ),김신규 ( Think You Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.2

Objective: Quantitative experiment and analysis of the result with statistical techniques are an essential part of the medical article for acquiring objective confidence. But errors on application, calculation, and interpretation of statistics and insufficient explanation of the used statistical technique deprive the reader of reliance on the article. We identified the statistical techniques and errors that were commonly encountered, and both of researchers and readers should recognize, in the Journal of the Korean Rheumatism Association (JKRA). Methods: We identified the frequency of the statistical techniques and errors from the 136 articles in the 1994~1998 editions of the JKRA. Each different kind of statistical techniques and errors in the same article were counted separately, but two or more of the same kind of statistical techniques and errors in an article were counted as one. Results: One hundred and seventy-seven statistical techniques were encountered and 75 statistical errors were identified. The most frequently used techniques were descriptive statistics, and common errors and the observed numbers of the errors were as follow: 1. performing statistical techniques for two groups on the comparison of three or more groups(14), 2. mentioning the statistical technique without using it(14), 3. using mean and standard deviation instead of median and range on the ordinal data(12), 4. using standard error instead of standard deviation for the description of data spread(11), 5. using p value without the statistical name(11). Conclusion: The most frequently encountered statistical technique and error are descriptive technique and performing statistical techniques for 2 groups on the comparison of 3 or more groups, respectively. The authors` careful application of the basic statistics would be the real solution to reduce the statistical errors.

Human parvovirus B19와 류마티스 관절염

전래희 ( Lae Hee Chun ),김신규 ( Think You Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.1

목적: Human parvovirus B19는 소아의 전염성 홍반의 원인 바이러스일 뿐 아니라 재생불량성발증, 선천성 태아수종, 급성 또는 만성 류마토이드양관절증 등 다른 질환을 일으키기도 한다. 최근 들어서는 human parvovirus B19와 RA와의 연관성에 관한 연구들이 보고되었다. 영국, 독일, 일본, 중국 등에서는 human parvovirus B19가 RA의 병발과 관련이 있다고 보고한 반면 북아일랜드, 핀란드, 프랑스 등에서는 관련이 없다고 보고하였다. 저자들은 국내 환자들을 대상으로 한국에서의 human parvovirus B19와 RA의 연관성에 대해 연구하였다. 방법: RA 환자 104명, OA 환자 40명, SLE 환자 32명의 혈청으로 anti-human parvovirus B19 IgG와 IgM에 대해 ELISA (Biotrin)로 검사하였다. 결과: RA 환자들과 비교하여 SLE 환자들과 OA 환자들의 human parvovirus B19 IgG 양성율이 통계적으로 의미있는 차이를 나타내지 않았다. IgM의 경우도 RA에서만 4명의 환자에서 양성을 보였고 SLE와 OA에서는 모두 음성이었다. 결론: 외국의 보고들 특히 주변국인 일본과 중국의 보고와 달리 한국에서는 human parvovirus B19 감염과 RA 사이에 연관성이 없다고 생각되었다. 이러한 차이는 결국 인종과 국가마다 집단의 항체 양성률이 다르기 때문으로 생각되었다. 그러므로 한국에서 RA 환자의 human parvovirus B19 항체 검사는 필요 없을 것으로 생각하였다. 결론적으로 RA 환자에 대한 human parvovirus B19 항체검사는 나라마다 적응과 결과해석을 달리해야 할 것으로 사료된다. Background: The pathogenic human parvovirus B19 is the etiologic agent of erythema infectiosum and causes other events including aplastic crisis, hydrops fetalis and fetal loss. Recently, it has been reported in many articles that human parvovirus B19 infection is associated with rheumatoid arthritis (RA). In contrast to these reports from the United Kingdom, Germany, Japan and China, different results were reported that there is no association between human parvovirus B19 and the pathogenesis of RA in Northern Ireland, Finland and France. This study aimed to investigate the association between human parvovirus B19 and RA in Korea. Methods: Sera from 104 patients with RA, 40 with osteoarthritis (OA) and 32 with systemic lupus erythematosus (SLE) were tested for IgG and IgM of human parvovirus B19 by ELISA (Biotrin), respectively. Results: There were no statistical differences among RA, OA and SLE patients in both anti-human parvovirus B19 IgG and IgM (p>0.05). Human parvovirus B19 IgM was positive in only four RA patients and negative in all SLE and OA patients. Conclusion: Human parvovirus B19 infection showed no association with RA in Korea, which is different from reports from other countries, especially Japan and China which are our neighbors. We thought that this result was due to the ethnic or national differences of baseline titer of anti-human parvovirus B19. Therefore anti-human parvovirus B19 test for RA patients is not necessary in Korea. In conclusion, we suggest that the indication and interpretation of anti-human parvovirus B19 testing in RA patients should be applied differently for each nation.

한랭글로불린의 조기결과 보고를 위한 연구

김종우 ( Jong Woo Kim ),전래희 ( La He Jearn ),김신규 ( Think You Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.2

Objective: Cryoglobulins are immunoglobulins that tend to form reversible precipitations below 37℃, well known to be associated with various diseases such as autoimmune diseases, hematologic malignancies, chronic infections and renal diseases. In many cases, low amounts of cryoglobulins take a few days to be precipitated. In this study, we compared cryoglobulin early screening test with conventional method to evaluate its clinical efficacy. Methods: 28 patients who showed cryoglobulinemia were selected and the time it took for visibly detecting the existence of cryoglobulin were recorded. Sera of cryoglobulinemiemic patients (n=19) and of control group (n=14) kept in two conditions of 37℃ and 4℃ for 1 hour and were then measured for delta optical density (DOD). Results: In the cryoglobulin early screening test using the test tube, the median and range of the DOD for cryoglobulinemic patient group was 0.50 (0.17∼0.99) while it was 0.18 (0.02∼0.50) for the control group. The results showed statistically significant difference (p=0.001). In another method of using the microplate, there was no statistical significance between disease and control group. The area under the curve for test tube method was 0.857. The sensitivity and specificity were 89.5% and 71.4% respectively (cut-off value=0.23). Conclusion: Cryoglobulin early screening test provides the results within 2 hours and we thought this feature could give clinicians some helpful informations. More studies are needed in the future for increasing the sensitivity and specificity of this test.

류마티스 관절염에서 항핵주변인자의 아형에 관한 연구

이혜림 ( Hye Rim Lee ),김신규 ( Think You Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.2

Objective: Antiperinuclear factor (APF) is regarded as a marker antibody with high sensitivity and specificity for rheumatoid arthritis (RA). However, the precise role of APF in the pathogenesis of RA has not yet been elucidated. Studying the isotype of APF may be a step in revealing the nature of this antibody, but such studies have been rare, and none have been done in Korea. The present study is set out to identify the isotype of APF from sera of Korean patients with RA, and to determine whether certain isotypes are related to specific clinical aspects. Methods: A total of 114 APF positive RA sera were tested against IgG, IgA and IgM separately by indirect immunofluorescence method, and the medical records were retrospectively reviewed. Results: All 114 serum samples were positive for IgG-APF, 100 positive for only IgG-APF (G group, 87.7%), 9 positive for IgG and IgA-APF (GA group, 7.9%), 4 positive for IgG and IgM-APF (GM group, 3.5%), and one sample was positive for IgG, IgA and IgM-APF (0.9%). The levels of rheumatoid factor (RF) and C-reactive protein (CRP) were different between the 3 groups (ANOVA test), and the RF and CRP of the GM group was higher than the other 2 groups (Bonferroni test). Conclusion: The APF identified in Korean patients with RA was always IgG-APF. IgM-APF may be used as a serological marker to assess disease activity in conjunction with CRP. The differences in the laboratory parameters between each isotype groups indicate the possibility of utilizing the isotype of APF to determine the disease activity or prognosis of RA.

류마티스 관절염 환자에서 Shared Epitope의 임상적 의의

민도식 ( Doh Sik Minn ),김신규 ( Think You Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.1

Objective: The application of DNA sequencing and molecular-based typing to detect HLA-DRB1 alleles showed that those associated with rheumatoid arthritis (RA) shared a consensus amino acid sequence (QKRAA or QRRAA) at positions 70-74 of the third hypervariable region of the HLA-DRB1 chain. This is defined as the so-called `shared epitope`. Many studies reported that shared epitope was associated with RA susceptibility and disease severity. Also, DRB1*0401 and DRB1*0404 alleles confer genetic predisposition to RA in Caucasian. We studied the frequency of shared epitope, DRB1*04, DRB1*0401, and DRB1*0404 in Korean RA patients using monoclonal antibodies. We also tried to investigate the influence of these factors on susceptibility and severity in RA patients and to evaluate the method. Methods: RA patients were 32 persons with classical or definite RA who attended the Hospital for Rheumatic Diseases, Hanyang University Hospital, Seoul, Korea. We separated lymphocytes from whole blood and used indirect immunofluorescence staining method using four monoclonal antibodies (Terra Nova, Canada). Results: The frequency of DRB1*04 and shared epitope were 56% and 56%, respectively. That of DRB1*0401 and DRB1*0404 were positive in 19% and 9% of all patients, respectively. There were no association between share epitope and disease severity. Conclusion: The shared epitope is expressed with high frequency, as many as DR4 frequency in Korean RA patients. But the frequency of DRB1*0401 and DRB1*0404 is low different from Caucasian. The used method is simple and easy to screen shared epitope.