• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.180-189
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• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1154-1166
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• 1998

Background : In the management of patients whose primary chemotherapy has failed, careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The purpose of present study is establishment of retreatment regimen for pulmonary tuberculosis. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Masan Tuberculosis Hospital. Methods : Retrospective cohort study was made of 104 drug-resistant pulmonary tuberculosis patients who were treated by five regimens between Jan. 1994 and Nov. 1996. All the patients taken medicine for second anti-tuberculosis regimens for the first time. We separated the patients by three groups(Group I ; OFX+PTA+CS+PAS+Aminoglycoside, Group II : PZA+PTA+CS+PAS+Aminoglycoside, Group III : PZA+OFX+PTA+PAS+Aminoglycoside). Results : The age distribution was most frequent in fourth decade(36patients, 34.6%) and the mean age was 42.6 year. The sex distribution was more frequent in the males(81 patients, 85.7%). There was 31 patients(29.8%) with combined diseaes, 18 patients with complication and 24 patients(27.9%) with family history. Primary chemotherapy regimens were HERZ(S or K) in 48 patients (46.2%), HER(S or K) in 41 patients(39.4%) and others in 15 patients(14.4%). Result of drug sensitivity test showed that the resistance to INH and RFP is in 68 patients(65.4%), RFP is 12 patients(11.5%), INH is in 3 patients(2.9%) and all sensitive to INH and RFP is 3 patients(2.9%). The clinical symptoms on admission were coughing(89.4%), sputum(69.2%), dyspnea on exertion(37.5%), weight loss(33.7%) blood tinged sputum(15.4%) and others. The extent of disease on the radiograph was far-advanced in 73 patients(70.2%), moderate in 28 patients(26.9%) and minimal in 3 patients(2.9%). The side effects for drugs were gastrointestinal troubles in 31 patients(29.8%), arthralgia in 22 patients(21.2%), skin rash in 12 patients(11.5%) and others. The negative conversion rate on sputum AFB smear was 85.6%(87.5% in Group I, 80.0% in Group II and 90.5% in Group III). The average negative conversion time on sputum was 4 month(4.0 month in Group I, 4.6 month in Group II and 3.0 month in Group III). Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and combination of PZA and OFX can be use effectively substituting for CS.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.129-134
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• 2005

Background : Ethambutol (EMB) is one of important first-line drug in the treatment of tuberculosis. Molecular techniques to detect embB gene mutations have been considered as an method to define the EMB resistance. We investigated the mutation rate within embB gene among EMB resistant strains using reverse hybridization techniques. Methods : We made 11 probes that had wild or mutated sequences containing codons 306, 406, or 497 within embB gene respectively. These probes were reverse-hybridized with PCR products amplified from embB gene which were isolated from 149 ethambutol resistant strains and 50 pan-susceptible strains. Results : Out of 149 ethambutol resistant strains, one hundred (67.1%) had mutation at least one base at codon 306, 406, or 497 in embB gene. Mutation at codon 306, 406, 497 were demonstrated in 75 (50.3%), 16 (10.7%), and 13 strains (8.7%) respectively. There were four strains that showed multi-mutation at codon 306 and codon 406 simultaneously. A high proportion (8.1%) had single mutation at codon 406. There was no mutation observed in embB gene among 50 pan-susceptible strains. Conclusion : Reverse hybridization will be useful technique for detection of gene mutation correlated to ethambutol resistance.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.2
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• pp.74-81
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• 2016

Ureaplasma species can normally colonize in the bodies of healthy individuals. Their colonization is associated with various diseases including non-gonococcal urethritis, chorioamnionitis, neonatal meningitis, and prematurity. In 2012, the sum of the resistant and intermediate resistant rates of Ureaplasma spp. to ofloxacin and ciprofloxacin was 66.08% and 92.69%, respectively. DNA point mutations in the genes encoding DNA gyrase (topoisomerase II) and topoisomerase IV are commonly responsible for fluoroquinolone resistance. Each enzyme is composed of two subunits encoded by gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV. In the current study, these genes were sequenced in order to determine the role of amino acid substitutions in Ureaplasma spp. clinical isolates. From December 2012 to May 2013, we examined mutation patterns of the quinolone resistance-determining region (QRDR) in Ureaplasma spp. DNA sequences in the QRDR region of Ureaplasma clinical isolates were compared with those of reference strains including U. urealyticum serovar 8 (ATCC 27618) and U. parvum serovar 3 (ATCC 27815). Mutations were detected in all ofloxacin- and ciprofloxacin-resistant isolates, however no mutations were detected in drug-susceptible isolates. Most of the mutations related to fluoroquinolone resistance occurred in the parC gene, causing amino acid substitutions. Newly found amino acid substitutions in this study were Asn481Ser in GyrB; Phe149Leu, Asp150Met, Asp151Ile, and Ser152Val in ParC; and Pro446Ser and Arg448Lys in ParE. Continuous monitoring and accumulation of mutation data in fluoroquinolone-resistant Ureaplasma clinical isolates are essential to determining the tendency and to understanding the mechanisms underlying antimicrobial resistance.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.546-557
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• 2000

Background : Oligonucleotide chip technology has proven to be a very useful tool in the rapid diagnosis of infectious disease. Rifampin resistance is considered as a useful marker of multidrug-resistance in tuberculosis. Mutations in the rpoB gene coding $\beta$ subunit of RNA polymerase represent the main mechanism of rifampin resistance. The purpose of this study was to develop a diagnosis kit using oligonucleotide chip for the rapid and accurate detection of rifampin-resistance in Mycobacterium tuberculosis. Method : The sequence specific probes for mutations in the rpoB gene were designed and spotted onto the glass slide, oligonucleotide chip. 38 clinical isolates of Mycobacterium were tested. A part of rpoB was amplified, labelled, and hybridized on the oligonucleotide chip with probes. Results were analyzed with a laser scanner. Direct sequencing was done to verify the results. Result : The low-density oligonucleotide chip design어 to determine the specific mutations in the rpoB gene of M. tuberculosis accurately detected rifampin resistance associated with mutations in 28 clinical isolates. Mutations at codons 531, 526, and 513 were confirmed by direct sequencing analysis. Conclusion : Mutant detection using oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of multidrug-resistance in M. tuberculosis.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.955-960
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• 2005

Resistance to metronidazole, a key component of therapies against Helicobacter pylori, is common in clinical isolates. Resistance generally requires inactivation of rdxA (HP0954), and sometimes also frxA (HP0642), two related nitroreductase genes. Here we studied the effect of resistance to metronidazole on fitness of the gastric pathogen H. pylori. The effect of metronidazole resistance for H. pylori in culture was assessed first by looking at colonies formed by freshly constructed mutant derivatives of H. pylori strain 26695. Mutations resulting in metronidazole resistance caused premature death of H.pylori in stationary phase, but had no significant effect on early exponential growth. The effect of nitroreductase deficiencies on fitness in vivo was tested by infecting C57BL/6 mice with 1:1 mixtures of SS1 wild type and its isogenic metronidazole resistant derivatives. Inactivation of rdxA caused an inability to colonize mice in SS1 H. pylori strain. Derivatives of a metronidazole resistant strain that survived better in stationary phase, although remaining metronidazole resistant, could again colonize mice. In conclusion, metronidazole resistance diminishes H. pylori's fitness, but their costs can be suppressed by additional mutation.

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.82-91
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• 2021

Background: The purpose of this study was to investigate the association between antibiotic use and the antimicrobial resistance of gram-negative bacteria isolated from blood cultures in a pediatric population. Methods: From January 2014 to June 2018, the antibiotic resistance pattern of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa obtained from bacteremic patients aged ≤18 years hospitalized at Asan Medical Center Children's Hospital was analyzed and the parenteral antibiotic consumption data were retrieved. Results: During the study period, the blood culture was positive for K. pneumoniae (6.4%; 105/1,628), E. coli (5.6%; 91/1,628), P. aeruginosa (3.3%; 54/1,628), and A. baumannii (2.5%; 41/1,628), and the extended-spectrum antibiotic resistance rate of gram-negative bacteria was consistently high. The overall resistance rate of E. coli and K. pneumoniae to extendedspectrum cephalosporin was 49.3% and 54.4%, respectively. Carbapenem-resistant E. coli was first detected in 2014; its overall resistance rate to carbapenem was 5.3%. There was a linear correlation between the usage of 3rd generation cephalosporin and the resistance of A. baumannii (r²=0.96, P=0.004) and carbapenem usage and the resistance of K. pneumoniae (r²=0.79, P=0.045). Conclusions: A positive linear correlation was observed between antibiotic resistance and the corresponding antibiotic usage in 3rd generation cephalosporin resistant A. baumannii and carbapenem resistant K. pneumoniae. The judicious use of antibiotics in healthcare settings is important to minimize selection for extended-spectrum β-lactamase (ESBL) and carbapenem resistance in gram-negative bacteria.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Biomedical Science Letters
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• v.3 no.1
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• pp.55-67
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• 1997

Considering many problems caused by the abuse of antibiotics recently, the appearance of antibiotic resistance bacteria is believed to help the cure of patients greatly. From Jan. 1st, 1996 to Dec. 31, 1996, 6135 strains were examined after being asked of and seperated from the clinical pathology departments of general hospitals, and the isolation frequency of identified bacteria and the susceptibility of antibiotics showed the following result. 1. The isolation frequency of strains was Escherichia coli, 1134 strains (18.4%), Pseudomonas aeruginosa, 856 strains (13.9%), coagulase negative Staphylococcus, 793 strains (12.89%), Staphylococcus aureus, 555 strains (9.02%), B. cepacia, 421 strains (6.84%), Enterobacter cloacae, 366 strains (5.95%), Enterobacter faecalis (4.86%), and Klebsiella pneumonia, 220 strains (3.85%). 2. The isolation rate of specimen was urine, 1, 969 strains, wound 1, 104 strains, sputum 701 strains, blood 643 strains, vaginal swab, 342 strains, and eye discharge, 192 strains, 40% of urine strains were E. coli 18％ of wound strains were B. cepacia, 43.7％ of sputum were P. aeruginosa, and in blood strains there were Enterobacter cloacae (25.8%), coagulase negative Staphylococcus (19.6%), and P. aeruginosa (8.7%). 3. The result of antibiotics susceptibility showed that, among gram negative bacilli, P. aeruginoas had resistance in almost all antibiotics except ceftazidme imipenem. But B. cepacia, the same glucose non-fermentation gram negative bacilli had more than 90％ of sensitivity in aztreonam, ceftazidime, ciproflxacin, piperacillin, trimethoprim/sulfa and had resistance in the others. Enterococcus faecalis showed more than 85% of sensitivity in penicillin-G, ampicillin, ciprofloxacin. 4. In the case of specimen antibiotics susceptibility, Enterobacter cloacae was lower in specimen isolated from blood than in those isolated from others and p. aeruginosa was low in specimen isolated from urine, which showed that there was difference in specimen antibiotics susceptibility. The result of this study shows that there happen many resisitances in antibiotics used frequently and some countermeasure is necessary because many bacteria began to show new resistance. Also it is desirable that the choice of antibiotics for infection diagnosis and its cure should be made after the inspection of antibiotics.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.29-41
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• 2001

Background : The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. Methods : In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. Results : Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. Conlcusion : An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drugsusceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.