• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Journal of Chest Surgery
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• v.35 no.11
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• pp.799-806
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• 2002

In spite of the establishment of chemotherapy and the gradual decrease in prevalence, pulmonary tuberculosis is still mainly treated with an operation. Through analyzing and examining some cases of surgical treatment, we hope to provide some help in treating of pulmonary tuberculosis in the future. Material and Method: By comparing four journals previously published in our department with 144 cases of lung surgery during ten years from January of 1991 to December of 2000 performed by the department of thoracic and cardiovascular surgery of the National Medical Center, we analyzed and reviewed the most recent trends and the results of the surgical treatment. Annual frequency of the operation, distribution of age, examination of sputum, adaptability and types of techniques, complications, and results of the postoperative follow-up were used as methods. Result: It was found that the annual frequency of operations had decreased. The ratio of men to women, 2:1 indicates that there are more incidences in men. Aging of patients could be speculated by the .results that the decrease in the incidence rate in the 20s age range and increase rate in the 50s age range. The range of preoperative lesions belonged mostly to far advanced and moderately advanced tuberculosis. By monitoring the period of use in preoperative antituberculosis drugs, cases for more than 3 years remarkably increased from 16.0 % to 55.6 %. The positive reactive rate for preoperative sputum examinations were drastically decreased from 91 % to 27 %. Total pulmonary destruction and partial destruction were the most common cases in terms of adaptability to the operations and there were significant increases in forming empyema accompanied by parenchymal lesions from 4.0 % to 20.1 %. Pneumonectomy and pulmonary lobectomy were the major type of operations. Especially, there were increases in the incident rate of empyema and recurrence of tuberculosis resulted. Post operative follow-up indicates that the rate of complete recovery was more than 70 % and the rate of gradual increase in treating with persistent antituberculosis drug was from 5.8 % to 18.0 %. Conclusion: In recent cases, there is an increasing number of patients showing tolerance to chemotherapy. Patients with pleural tuberculosis and severe lesions were typically increased. It is important to accurately analyze those complaints accurately that are mostly difficult to be treated medically. Surgical treatment is strongly recommended Before multiple drug resistance occurs.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.852-861
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• 1996

Background : Many clinicians have experienced the difficulty of decision on termination of antituberculosis chemotherapy after the 6th month due to relapse of disease. There is still controversy in the effect of 2S(K)HRZ/4HRZ 6-month short course chemotherapy including pyrazinamide for 6 months in patiems with pulmonary tuberculosis. And there is no long term follow-up study of 6-month short course chemotherapy for pulmonary tuberculosis in korea. So we had performed the study to find the result of 6-month antituberculosis chemotherapy for 4 years. Method : We studied prospectively the effect of 2S(K)HRZ/4HRZ in one hundred-fifty patients with pulmonary tuberculosis and followed up fifty-nine patients for more than 1 year to 4 years after the completion of 6-month short course therapy. Results : 1) Out of one hundred-fifty patients, seventy-two patients(48%) completed the prescribed 6-month chemotherapy. Sixty-eight patients(45.3%) have experienced premature discontinuation and the most common cause of premature discontinuation was drop-out against advice(thirty-six patients, 24%). Ten patients(6.7%) were treated beyond the 6 months mainly due to irregular treatment. 2) Fifty-nine patients(81.9%) among seventy-two patients with completed treatment have been followed up for more than 1 year and 32 patients(44.4%) for more than 4 years. There was three relapse patients of whom two patients have experienced relapse of pulmonary tuberculosis within 1 year after the termination of chemotherapy. 3) Among one hundred-thirty-four patients who have been assessible for more than two months of chemotherapy, including the patients who experienced within 2 months, there were eighty-two patients(61.2%) who have experienced adverse reactions and the treatment regimen was changed only in thirteen patients(9.7%). The most frequent cause of adverse reactions was arthralgia and/or hyperuricemia, which had occurred in 33 patients(24.6%). Conclusion : In a university hospital in Korea, 6-month shot course chemotherapy of 2S(K)HRZ/4HRZ had unnegligible relapses and premature discontinuation. Therefore, change of the regimen might be carefully considered by drug susceptibility results. Close monitoring of patients, retrial of sputum exam and radiologic evaluation during treatment might be required in the endemic area of drug resistant strains like in Korea. Further study about the effect of 6-month short course chemotherapy including pyrazinamide for 6-month might be needed.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.295-301
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• 1995

Background: The serious problems in retreatment of pulmonary tuberculosis are a significant proportion of drug resistance. Preferably retreatment should contain the drugs which has never used before, so drug retreatment is limited in selection. A new antibacterial substance, ofloxacin(OFX) is the activity against mycobacterium tuberculosis and it has been used in the treatment of pulmonary tuberculosis. The present report concerns the result of retreatment of pulmonary tuberculosis patients containing OFX treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow up of 92 smear positive cases, who were treated by four drugs regimen between Mar 1991 and June 1994 at National Kongju Tuberculosis Hospital. Four drugs were, namely prothionamide, cycloserine, ofloxacin and streptomycin(kanamycin or tuberactinomycin). The duration of follow up was over one year. Results: 1) Out of 92 cases with positive sputum AFB smear, 67(73%) achieved the negative conversion. 2) Considering the negative sputum conversion in all the groups, the vast majority(85%) of sputum conversion occurred within the first 4 months. 3) The roentgenological improvement occurred in 49 percent on the whole and when the extent of disease was minimal, moderately, far advanced pulmonary tuberculosis, sputum AFB smear negative response to retreatment was 100%, 93%, 68%, respectively. 4) When the duration of patient's illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 87%, 76%, 65% and 55%, respectively. 5) Adverse reaction to prothionamide, with complaints of gastrointestinal troubles was common and hepatic dysfunction without jaundice was observed in 7 percent, convulsion in 1 percent, that to cycloserine occurred renal dysfunction & psycosis & convulsion, 2%, 1%, 1%, respectively. Tinnitus with KM occurred in 1% and dirrhea with OFX in 4%. Conclusion: The duration of patient's illness was shorter, sputum AFB smear negative response rate was better. Radiologic responses were not remarkable, but extent of disease by national tuberculosis association was smaller, the result of retreatment was better. Adverse reaction of the secondary antituberculosis agent was mainly observed gastrointestinal troubles, as regard to tolerance to the secondary drugs the role of the physician is of very important value and toxic effects can be overcome by the strong confidence.

• Journal of Chest Surgery
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• v.29 no.4
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• pp.397-402
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• 1996

A clinical study of 36 cases of pulmonary tuberculosis that had had a surgical resection during the period of 13 years from January 1979 to December 1992 was performed in the Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Hospital The ratio between male and female was 3.5 1 and the age of peak incidence was in the 2nd and 3rd decades. The common prodromal symptoms were chest pain (38.9 %) and hemoptysis or blood tinged sputum (36.1 %). Preoperative diagnostic examination of sputum positivity for AFB stain despite antituberculosis chemotherapy was noticed in 22.8 oyo . Surgical indications were destroyed lobe or segment with or without cavity (58.3 oyo), mass unable to differentiate from lung cancer (16.7 %), total destroyed lung (13.9 %), bronchostenosis with atelectasis and distal bronchiectasis (11.1 %). Types of resection were pneumonectomy in 16.7%, lobec omy and segmentectomy 2.7%, lobectomy 50 %, segmentectomy 27.8%, and wedge resection 2.7%. Postoperatively, pulmonary function Improved compared to the preoperative examination, although these changes were not statistically significant. One patient died of ulcerative colitis due to drug hypersensitivity, and the postoperative complications were remnant dead space in 11.1 %, spreading of tuberculosis in 5.5%, and empyema with BPF in 5.5%.

• Pediatric Infection and Vaccine
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• v.15 no.2
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• pp.167-173
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• 2008

Purpose : We evaluated the prevalence and clinical, microbiological features of extrapulmonary tuberculosis (EPT) in pediatric patients. Methods : We retrospectively reviewed medical records of pediatric patients diagnosed with EPT at The Catholic University of Korea, Incheon St. Mary's Hospital between 2000 and 2007. Results : Of 109 patients diagnosed with tuberculosis (TB), 12 patients (11%) were admitted with EPT. At 2006-2007, the proportion of patients with EPT among patients with TB was the highest (20%) comparing with last 6 years. The ratio of male to female patients was 1.4:1 and the mean age was 9.2 years (range, 3 months-15 years). The involved sites were pleura in 5 (41.6%), central nervous system in 3 (25%), miliary TB in 2 (16.7%), gastrointestinal tract in 1 (8.3%) and bone and joint in 1 (8.3%). The most common symptom at admission was fever (91.6%) and mean duration of fever was 15.8 days (range, 0-47 days) in spite of the proper treatment. Confirmed rate for acid fast bacillus stain, culture, and polymerase chain reaction were 33.3%, 41.6% and 41.6%. Of 5 culture proven cases, 4 (80%) were resistant to more than one antituberculosis drugs. Eleven patients recovered without complication and 1 patient died. Conclusion : Total incidence of TB decreased steadily according to the nationwide survey. However, our results suggest that the proportion of diagnosis with EPT among diagnosis with TB in children has increased. Microbiological diagnosis of EPT in children was more difficult than that of pulmonary TB. And drug resistance rate has increased.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.241-250
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• 1997

Objective : Although the prevalence of pulmonary tuberculosis has decreased progressively after the national control program for tuberculosis began, nowadays the number of MDRTB is increasing seriously. MDRTB tends to be poor responsive to current antituberculosis regimens. It is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. The purpose of present study is to evaluate the clinical features of pulmonary tuberculosis patients admitted in one national tuberculosis hospital and to expose the problems pertaining to current remedies, to increase the treatment efficacy for pulmonary tuberculosis including MDRTB in the end. Method : Retrospective analysis of 336 pulmonary tuberculosis patients admitted in National Masan Tuberculosis Hospital was done. Contents of analysis were patients profile, the first diagnosed time and medical institutes, family history, residence, previous treatment history, chief complaints at the time of admission, lesion site on chest X -ray film, combined deseases, side reaction to antibuberculosis drugs, used drugs before admission and the results of drug sensitivity test. Results : The ratio between male and female was 4 : 1. Age showed relatively even distribution from 3rd to 6 th decades. 64.6% of the patients was diagnosed at public health center. Weight loss was the most common complaint at admission. Bilateral lesions on chest X-ray films were 59.8%. 130patients had combined desease, of which DM was the most common(37.7%). 95patients had family history, of which parents were the most common(41.7%). According to the time of first diagnosis, 31 patients were diagnosed before 1980, and after then the number of patients was increased by degrees. Residence overwhelmed in pusan and gyung-nam province. 258 patients got previous treatment history, of which 112 patients(43.4%) had more than 3 times and only 133 patients(51.6%)got regular medication. 97 patients used more than other 3 drugs in addition to INH, EMB, RFP and PZA before admission. 154 patients were informed with the results of drug sensitivity test. of which 77 patients had resistance to more than 5 drugs. Gastrointestinal problem was the most common in side reaction to drugs. Conclusion : In the case of weight loss of unknown cause, tuberculosis should be suspected. In first treatment, sufficient and satisfactory explanation for tuberculosis is necessary and treatment period should not be stict to 6 month-short term therapy. In retreatment, new drugs should not be added to used drugs even though drug sensitivity results show sensitivity to some of them. Proper time for surgical intervention should not be delayed.