• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.8-14
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• 2008

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was $14{\pm}7$ days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was $34{\pm}21$ days and in the hospital $58{\pm}52$ days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.42 no.1
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• pp.68-78
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• 1997

Laboratory and greenhouse studies were conducted to determine differential sensitivities on absorption of $^{14}$ C-oxyfluorfen and the anatomical responses in wheat and barley to protoporphyrinogen oxidase-inhibiting herbicides [oxyfluorfen (2-chloro-1- (3-ethoxy -nitrophen-oxy)-4-(trifluoromethyl) benzene, acifluorfen(5-[2-chloro-4-(trifluoromethyl) phenoxy]-2-nitro-benzoic acid), bifenox(methyl-5-(2, 4-dichlorophenoxy)-2-nitrobenzoate) and oxadiazon(5-tert-butyl-3-(2, 4-dichloro-5-isopropoxyphenyl)-1, 3, 4-oxadiazol-2-one)]. I$_{50}$ value of the tolerant wheat cultivars to oxyfluorfen was about 10$^{-4}$ , whereas that of the susceptible barley cultivars was about 10$^{-6}$ M, showing significant difference between the two groups. When foliage were applied with acifluorfen, bifenox or oxadiazon, the oxyfluorfen-tolerant wheat showed less decreased in shoot fresh weight and chlorophyll content than the susceptible barley. Also, when soil-applied with these herbicides test plants showed similar tendency in foliar application. Electrolyte leakage from the tissue treated with these compounds was the more influenced in the barley than the wheat. Malondialdehyde(MDA) production as index of lipid peroxidation was greater in the barley than the wheat by treatment of these compounds. Therefore, the differential sensitivities of wheat and barley to protoporphyrinogen oxidaseinhibiting herbicides was showed by our greenhouse and in vitro experiment. The absorption rates of $^{14}$ C-oxyfluorfen were higher in the barley than the wheat. And this tendency was showed appararitly difference by increase of treatment durations. After the oxfluorfen and oxadiazon treatment, the tolerant wheat did not show the structural damage in leaf surface, but the susceptible barley was damaged in the leaf waxy layer. However, the acifluorfen and bifenox treatment showed no difference between wheat and barley. The anatomical changes by these compounds treatment were not observed in the tolerant wheat but epidermal cell and mesophyll cell were highly broken in the susceptible barley.

• Journal of Life Science
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• v.27 no.2
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• pp.149-154
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• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.735-746
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• 1999

Background: As the prevalence of nontuberculous mycobacteriosis has been increasing rapidly, there has been recent advance in diagnostic methods and drug therapies for disease. Although the incidence of pulmonary disease caused by nontuberculous mycobacteria(NTM) has been increasing in Korea since 1990, detailed clinical description about the disease were very few. In this study we described the clinical manifestations, radiologic findings, and therapeutic outcomes of nontuberculous mycobacterial pulmonary disease. Methods: Medical records and radiologic findings were retrospectively reviewed in 27 patients who were fulfilled the diagnostic criteria of ATS guideline for NTM pulmonary disease between January of 1990 and August of 1998 in Seoul National University Hospital(SNUH). Results: Of the 27 patients, 15 were male. The mean age was 51.5 yr($\pm$11.9). Twenty patients(74.1%) had preexisting pulmonary diseases. Among them, 19 patients had previous pulmonary tuberculosis. Sixteen patients(59.2%) had cavitary lesions and the majority showed slow progression over 1 yr during follow up period on radiography. Susceptibility test to standard antituberculous drugs showed 100% resistance to INH, 72.2% to RMP, 81.5% to EMB, 92.6% to PZA. The average resistance rate to 2nd-line antituberculous drugs was 66.1%. Among twenty-one patients(77.8%) who received drug therapy over 6 months, 11 subjects were improved and 10 subjects were aggravated. Of six subjects(22.2%) without therapy, 5 patients were aggravated. Presence of cavity and less than 3 sensitive drugs in the regimen were indicators for adverse outcome. Conclusion : The nontuberculous mycobacterial pulmonary diseases in our hospital developed predominantly in older patients with preexistent pulmonary disease. The results of antituberculous drug therapy has been frustrating and disappointing. To improve treatment response, different susceptibility tests and drug regimens for different species of NTM should be performed. Also, diagnostic and therapeutic guidelines of Korea should be made in the recent future.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.871-881
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• 1996

Objective: In the early short-term therapy of pulmonary tuberculosis, PZA is used for the first two months on 6EHRZ therapy but PZA is not effective in the case of long-tenn use PZA for retreatment in the sensitive relapse or acquired drug resistance for PZA. But in the endemic area as Korea, if we can't use PZA in the retreatment of pulmonary tuberculosis, we can't expect the success for retreatment of pulmonary tuberculosis, therefore we need new drugs substituting for PZA. In these days, 4 - fluoroquinolone derivatives were investigated and only ofloxacin and ciprofloxacin of derivatives were known to be effective but the effectiveness was also not certain because the result was experimental or combined with other bacteriocidal drugs and datas on effectiveness of pulmonary tuberculosis were so little. Therefore these drugs should be use with other two or three strong-acting drugs in the last period of retreatment of pulmonary tuberculosis. The ofloxacin or ciprofloxacin is used in some area in Korea but randomly and needed more study. We did this study for proving the effectiveness of these drugs and establishment of retreatment regimen for pulmonary tuberculosis. Methods: Retrospective cohort study of 83 drug-resistant pulmonary tuberculosis patients at National Masan Tuberculosis Hospital from Jan. 1994 to dec. 1995 was made. All the patients taken medicine for 2nd ami-tuberculosis regimens for the first lime. We separated the patients by two groups.(Group I : OFX+ PTA + CS+PAS + Injection, Group II: PZA + PTA+ CS + PAS + Injection). We compared the difference between two groups and tested the confidence limit about results after treatment by $\chi$2-test and T-test. Results : 1. The age distribution was most frequent in fourth decade(29.2% in Group I, 37.1% in Group II) and the mean age was 43.9 year in Group I, and 39.0 year in Group II, but had no significant difference between two groups. The sex distribution was more frequent in the males(68.8% in Group I, 85.7% in Group II), but had no significant difference. 2. Family history was 29.2% in Group I, 28.6% in Group II, but had no significant difference. 3. In the respect of extent of disease, far-advanced stare was 60.4% in Group I, 74.3% in Group II, but had no significant difference. 4. The side effects for drugs showed in 58.3% in Group I and 65.7% in Group II, and the gastrointestinal trouble showed 25.0% in Group and arthralgia 34.3% in Group II predominantly respectively and had the significant difference(p<0.05). 5. The negative conversion rate on sputum AFB smear was 87.5% in Group I and 80.0% in Group II, but had no significant difference. But the negative conversion rate on sputum AFB culture was 83.3% in Group I and 57.1 % in Group II and had the significant difference(p<0.05). 6. The success rate of treatment was 87.5 % in Group I and 83.3 % in Group II but had no significant difference. Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and can be use effectively substituting for PZA.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.143-149
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• 2008

Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.225-232
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• 2021

This study sought to investigate the distribution, antimicrobial resistance rate, and bacterial co-infection frequency of non-tuberculous mycobacteria (NTM) in a single center in Incheon, South Korea. A total of 8,258 specimens submitted for tuberculosis (TB)/NTM real-time PCR tests during the years 2015 to 2020 were retrospectively reviewed. In total, 296 specimens (3.6%) were NTM positive, and the positivity increased from 2.5% (30/1,209) in 2015 to 3.8% (66/1,740) in 2020. Of 296 NTM specimens, 54.7% (162/296) were identified as the Mycobacterium avium complex (MAC) followed by the Mycobacterium abscessus complex (MABC) 20.9% (62/296), M. fortuitum 6.4% (19/296) and M. flavescens 3.4% (10/296). Of the NTM-positive specimens, 76.7% (227/296) were tested for drug resistance. The results showed multidrug-resistant NTM in 40.1% (91/227) and extensively drug-resistant NTM in 59.9% (136/227) of these specimens. Of the 145 isolates taken for bacterial culture, bacteria/fungi co-infection with NTM accounted for 43.4% (63/145), in which the most common bacterial species was Klebsiella pneumonia (23.8%, 15/63). This study is the first report on the distribution and antimicrobial resistance of NTM in Incheon. As the proportion of NTM infections increases, active treatment and thorough infection control are required for effective management.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.484-492
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• 2001

Background : Pulmonary tuberculosis with a remaining cavitary lesion is considered to be a problem with the course of treatment. In particular, re-treatment cases tend to respond poorly to current anti-tuberculosis agents. Therefore the factors that are related with the poor closure of a cavitary lesion in pulmonary tuberculosis during treatment were evaluated. Methods : A retrospective review of the medical records and chest X -ray films of 68 patients who had chemotherapy for the pulmonary tuberculosis with cavitary lesions was made. All the patients had been followed up for more than 12 months at National Masan Tuberculosis Hospital as of Aug. 2000. Results : The male to female ratio was 3.9:1.72.4% of the patients were between 20 to 50 years of age. 66.2% of the cavitary lesions on the chest X-ray films were confined to the upper lung fields : 36.8% in the right upper lung field and 29.4% in the left upper lung field. 82.4% of the cavities were less than 40 mm in their size, and 83.8% were less than 6 mm thick. The cavitary lesions were closed in 48 cases and remained in 20 cases during a follow-up period of more than 12 months. The factors that are thought to affect to the outcomes of the cavities were age, past medication history, the number of unused drugs, and the number of sensitive drugs. Conclusion : In the treatment courses of pulmonary tuberculosis with cavitary lesions, the following factors are associated with less desirable outcome:an age over 45, a past medication history of more than 2 courses of treatment, The number of unused drugs not exceeding average 6 and the number of sensitive drugs not exceeding average 7.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1143-1153
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• 1998

Background : Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuberculosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the management of multidrug-resistant tuberculosis. Method : A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findings : (1) patients who have reasonably localized lesion (Localized Lesion Group ; LLG) (2) patients who have cavitary lesions after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG) (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multi drug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. Results : Seventy five point six percent were men and 24.4% women with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients(90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25. 7 months. The mean length of postoperative drug therapy of LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. Conclusion : Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failure or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all of them could not be resected perfectly, you should not open the thorax.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.