• Journal of Chest Surgery
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• v.34 no.5
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• pp.377-385
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• 2001

배경: Cisplain과 같은 세포돗성 약제에 대한 내성은 폐암 치료 실패의 중요한 원인이다. 이러한 항암제에 대한 내성의 발생기전은 복잡하고 아직 완전히 알려져 있지 않지만 불량한 예후의 원인으로 생각된다. 특히 약제 내성이 발생한 환자의 경우 기존의 종양의 급속한 성장뿐 아니라 새로운 전이 병소가 급속히 발생 및 진단됨은 약제 내성을 가진 종양이 전이에의 용이성을 획득하는게 아닌가 의심케한다. 이를 규명하기 위해 Cisplatin에 내성을 지닌 비소세포폐암 세포주 H460/CISm이 전이 능력을 Cisplatin에 민감한 비소세포폐암 세로주 H460과 비교하고자 한다. 대상 및 방법: 약제 내성 세포주를 확보하기 위하여 H460세포에 cisplatin을 점차적으로 증가시켜 처리한 후 배양하였다. H460 세포와 H460/CIS 세로에서의 혈관신생인자와 성장관련인 자의 발현양상, gelatin zymography 분석 그리고 in vivo 실험으로 nude 마우스에서의 자발적 전이 능력의 차이를 비교하였다. 결과: H460 세포를 이식한 마우스에 폐에서는 종양이 형성되지 않았으나 H460/CIS세포를 이식한 마우스 10마리중 8마리에서 종양이 형성되었다. 또한 H460/CIS 세포주에서 전이 관련 유전자로 알려진 angiopoietin-1, vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2 등이 더 발현되었고, 전이의 침습성을 유발하는 gelatinase의 활성이 증가된 것을 확인할 수 있었다. 결론: 본 여구 결과를 통해 cisplatin에 내성을 가진 비소세포폐암세포에서 전이 능력이 증가될 수 있다고 여겨지며 이러한 사실을 토대로 초기 비소세포폐암 환자의 수술 전 항암약물요법의 타당성에 대해서 이야기 하기 위해서는 많은 임상적 연구가 필요하리라 생각된다.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.311-316
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• 1999

Background: The drug-resistant tuberculosis has recently decreased in Korea, but it is still one of the major obstacles in the treatment of pulmonary tuberculosis. Unfortunately there are no reliable ways to figure out the drug sensitivity pattern of the M. tuberculosis in the starting point of treatment. At least several months which is critical for the success of treatment have to be passed away before getting the report of drug-sensitivity test. The aim of this study was to find out the clinical and radiological parameters that make it possible to predict the drug-resistant pulmonary tuberculosis and to make a correct decision on the antituberculosis drug regimens. Method: We studied 253 pulmonary TB patients with sputum and/or bronchial washing fluid culture-positive diagnosed at the Chung-Ang University Young-San Hospital in the period of 1989-1994. The differences in the clinical and raiological variables between the drug-sensitive and the drug-resistant tuberculosis patients were evaluated. Results: In 66 out of 253 patients(26.1%), drug resistant tuberculosis to at least one antituberculosis drug were found. Patients with retreatment showed higher resistance rate than those with initial treatment(30/69, 43.5% vs 36/184, 19.5%, p<0.01). Patients with cavitary TB showed higher resistance rate than those with non-cavitary TB(24/54, 44.4% vs 42/199, 21.1%, p<0.05). Among patients with initial treatment, those with far-advanced TB showed a higher drug resistance rate than those with minimal lesion(9/23, 36.9% vs 10/82, 12.5%, p<0.05). Patients with culture positive only in the bronchial washing fluid showed lower resistance rate than those with sputum culture positive(7/63, 11.1 % vs 59/190, 31.1%, p<0.05). Conclusion: Prior treatment history for pulmonary tuberculosis, the presence of cavity & far advanced tuberculosis in the radiologic exam, sputum rather than solely bronchial washing culture positivity would be the related factors to the drug resistance. So in the patients with such characteristics, it is needed to try to find out the drug sensitivity pattern of the infecting tuberculosis organism as soon as possible.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.23-30
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• 2011

Purpose : Acinetobacter baumannii is an aerobic, gram negative coccobacillus. Due to its pathogenicity and ability to accumulate diverse mechanisms of resistance, the importance of this organism is increasing. Many reports have targeted adults, and studies of pediatric patients are limited. This study aims to investigate the current status of A. baumannii infection in children. Methods : From January 2001 to December 2008, 505 patients hospitalized with A. baumannii infection were enrolled. Admission records for underlying disease, duration of hospitalization, previous antibiotic use, location of admission, presence of ventilator care, and resistance to antibiotics were retrospectively reviewed and analyzed. Results : Hemato-oncological disease and neurological disease were 30.6% and 24.3% of all cases; therefore, these were the most common underlying diseases of patients with A. baumannii infection. Prevalence of A. baumannii infection was 78.1% in patients with previous antibiotic use, which was higher than that of the group not using previous antibiotic. And prevalence of multi-drug resistant and pan-drug resistant A. baumannii infection was 76.4% and 38.3% in patients with ICU care, 76.8% and 38.9% with ventilator care, and these were higher than the others. Rate of resistance to all groups of antibiotics showed a gradual increase to over 50% in 2008. Multi-drug resistant A. baumannii was 63.5% and pan-drug resistant A. baumannii was 48.2% of all cases. Conclusion : Prevalence of A. baumannii infection and resistance to antibacterial agents of A. baumannii is increasing. Adequate use of antibiotics and infection control should be emphasized in pediatric patients.

• Tuberculosis and Respiratory Diseases
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• v.58 no.3
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• pp.243-247
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• 2005

Background : The prevalence of tuberculosis is slowly decreasing in Korea. However, the drug-resistance of pulmonary tuberculosis is a major risk factor of treatment failure. Moreover, the National Surveillance System has recently been discontinued. Therefore, a continuous survey is necessary for the exact detection of the rate of drug resistance. We studied the recent 4-year drug resistance rate of tuberculosis at a single University hospital in Seoul. Materials and Methods : The study included 239 pulmonary tuberculosis patients performed with a tuberculosis culture and a drug-sensitivity test at Hanyang University Medical Center from March 1999 to March 2003. Results : Of the 239 patients included in the study during the 4-year period, 52 patients showed resistance to one or more anti-tuberculosis drug (21.8%). The rate of multi-drug resistance was 12.6%. The resistance rates to isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were 18.4%, 13.8%, 11.7%, 6.7% and 8.4%, respectively. Ninety patients had a history of previous anti-tuberculosis treatment, and the rates of the overall drug resistance and multi-drug resistance of these patients were 36.7% and 25.6%, respectively. The patients with drug-resistance showed a higher rate of a previous tuberculosis treatment history (63.5%) than the drug-sensitive group patients (30.5%). Conclusion : The rate of drug resistant tuberculosis is 21.8%, and multi-drug resistant tuberculosis is 12.6%. The rate of drug resistance is higher in those previously treated for tuberculosis.

• Journal of Yeungnam Medical Science
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• v.9 no.1
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• pp.75-89
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• 1992

The development of multi drug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell(SNU-1/$Cis_5$) was induced from human stomach cancer cell line(SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/$Cis_5$, We compared the value of $IC_{50}$ - drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNU-1/$Cis_5$ were as follows; vinblastine, > 43.0 ; epirubicin, 22.9 ; dactinomycin, 16.0 ; etoposide, 15.0 ; vincristine, 9.2 ; adriamycin, 5.7 ; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of $10{\mu}M$ verapamil for SNU-1/$Cis_5$ were as follows; vincristine, 13.1 ; epirubicin, 10.0 ; etoposide, 6.3 ; vinblastine, 4.4 ; dactinomycin, 3.6 ; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.470-478
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• 1997

Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.

• Korean Journal of Agricultural Science
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• v.10 no.2
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• pp.200-205
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• 1983

Transfer experiment of drug resistance and citrate utilizing ability were performed to show the relationship between drug resistance and citrate utilizing ability of 76 Citrate-Utilizing variants of Escherichia coli(Cit $^+E$. coli) isolated from cattle. The results obtained were summarized as follows; 1. Of seventy-six Cit $^+E$. coli, 36(47.4%) strains transfered their drug resistance to the E. coli ML 1410 by mating. 2. Tetracycline(TC) resistance determinants and citrate utilizing ability were transmitted in the recipient strains selected for TC, but it can be seen the segregation of streptomycin (SM) resistance determinants and citrate utilizing character in 9 recipient strains selected for SM. 3. Of seventeen TC resistance Cit $^+E$. coli, 10 strains transfered citrate utilizing character, alone. 4. The transmission of the ability to utilize citrate on Simmons citrate agar at $37^{\circ}C$, was demonstrated 52(68.4%) out of the 76 Cit $^+E$. coli.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.47-51
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• 2004

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance Is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By using adriamycin-resistance CL02 cancer cells, we undertook the screening fur agents which were effective to multidrug-resistant cancer cells from strains of the species Sorangium cellulosum isolated in our laboratory. Sorangium cellulose, cellulose-degrading myxobacteria have recently proved to be a rich source of novel anticancer agents. One of the significant examples is the promising anticancer agent epothilone. JW 1006 is the first strain of Sorangium cellulosum which was selected by us for the isolation of a metabolite by a biological screening because of a high cytotoxic activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation of the culture broth led to the Isolation of two active principles, disorazole $A_1$ and $A_2$. They showed potent cytotoxicity against CL02 cancer cells with $IC_{50}$ values in the picomolar range, and were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.416-425
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• 2001

Background : The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. Methods : The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. Results : The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently associated with a history of previous treatment(odds ratio; 9.43, 9.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio; 2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio; 4.17 and 4.81 respectively, p<0.05). Conclusion : This study revealed that patients with a prior treatment history for pulmonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.422-426
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• 2008

Background: Mycobacterium abscessus is the most pathogenic and drug-resistant rapid-growing mycobacterium. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents that have an effect on M. abscessus. We tried to detect the clarithromycin-resistant strains from the clinical isolates of M. abscessus. Methods: We tried to isolate the clarithromycin-resistant strains from 220 clinical isolates of M. abscessus by performing using reverse hybridization assay (RHA) and the broth microdilution test (BMT). Results: Seven resistant strains (3.2%) from all the tested clinical isolates were detected by BMT. Three of these resistant strains were also detected by RHA and it was confirmed that they had point mutants. Conclusion: These results showed that clarithromycin resistance in M. abscessus clinical isolates is related to a point mutation and other unknown mechanisms.