• International Journal of Oral Biology
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• v.48 no.1
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• pp.1-7
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• 2023

Oral squamous cell carcinoma (OSCC), which accounts for approximately 90% of oral cancers, has a high rate of local recurrence and a poor prognosis despite improvements in treatment. Exosomes released from OSCC cells promote cell proliferation and metastasis. Although it is clear that the biogenesis of exosomes is mediated by the endosomal sorting complex required for transport (ESCRT) machinery, the gene expression pattern of ESCRT, depending on the cell type, remains elusive. The exosomal release from the human OSCC cell lines, HSC-3 and HSC-4, and their corresponding gefitinib-resistant sub-cell lines, HSC-3/GR and HSC-4/GR, was assessed by western blot and flow cytometry. The levels of ESCRT machinery proteins, including Hrs, Tsg101, and Alix, and whole-cell ubiquitination were evaluated by western blot. We observed that the basal level of exosomal release was higher in HSC-3/GR and HSC-4/GR cells than in HSC-3 and HSC-4 cells, respectively. Long-term gefitinib exposure of each cell line and its corresponding gefitinib-resistant sub-cell line differentially induced the expression of the ESCRT machinery. Furthermore, whole-cell ubiquitination and autophagic flux were shown to be increased in gefitinib-treated HSC-3 and HSC-4 cells. Our data indicate that the expression patterns of the ESCRT machinery genes are differentially regulated by the characteristics of cells, such as intracellular energy metabolism. Therefore, the expression patterns of the ESCRT machinery should be considered as a key factor to improve the treatment strategy for OSCC.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.38-47
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• 2012

Background: The prevalence rate of pulmonary tuberculosis (PTB) is steadily decreasing in South Korea. However, PTB is a disease with relatively high mortality and morbidity rates throughout Korea. Although there are many studies and statistics about the risk factors of PTB mortality in many countries, there are only a limited number of domestic papers on this topic. The aim of this study is to determine predictive factors for mortality among in-hospital patients associated with PTB. Methods: From December 2006 to January 2011, we reviewed medical records of 2,122 adult patients diagnosed with tuberculosis at a single tertiary hospital in a suburban area. In this study period, 960 patients were diagnosed with PTB by positive Acid fast bacilli smear and/or mycobacterial culture of the respiratory specimen. We compared the groups of patients deceased and patients discharged alive with PTB. The number of dead patients was 82 (47 males, 35 females). Results: Mortality was significantly associated with increased values of white blood cells (WBC), blood urine nitrogen (BUN), creatinine, C-reactive protein (CRP), numbers of involved lung field, and length of hospitalization. Also, it was associated with the decreased values of hemoglobin, lymphocyte, sodium, albumin, and cholesterol. Furthermore, admission through the emergency department, initial intensive care unit admission, and drug resistant PTB affected mortality in PTB patients. Independent predictors associated with PTB mortality are BUN, initial intensive care unit care, and admission during treatment of tuberculosis. Conclusion: In our study, mortality of pulmonary tuberculosis was related with parameters associated with nutritional status, disease severity at the time of admission, and drug resistance.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.287-293
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• 1999

Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

• Biomedical Science Letters
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• v.12 no.3
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• pp.153-160
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• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.

• Parasites, Hosts and Diseases
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• v.53 no.1
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• pp.35-41
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• 2015

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time ($22.5{\pm}10.6hr$) and the mean parasite clearance time ($27.3{\pm}12.2hr$) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P<0.0001). The resistance intensities decreased as follows: chloroquine>piperaquine>pyronarididine>artesunate. The inhibitory dose 50 ($IC_{50}$) was $3.77{\times}10^{-6}mol/L$, $2.09{\times}10^{-6}mol/L$, $0.09{\times}10^{-6}mol/L$, and $0.05{\times}10^{-6}mol/L$, and the mean concentrations for complete inhibition (CIMC) of schizont formation were $5.60{\times}10^{-6}mol/L$, $9.26{\times}10^{-6}mol/L$, $0.55{\times}10^{-6}mol/L$, and $0.07{\times}10^{-6}mol/L$, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.228-234
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• 2006

Background : Acinetobacter baumannii is an important pathogen associated with nosocomial infections in intensive care units, and is responsible for nosocomial pneumonia, UTI, bacteremia, etc. The main concern is that this pathogen is often resistant to many antimicrobial agents, particularly to carbapenem. This study compared the clinical those of ICU admitted patients with the carbapenem resistant A. baumannii isolated from the sputum with characteristics of patients with carbapenem sensitive A. baumannii. Methods : A total of 49 patients with A. baumannii from a sputum culture who were admitted to the ICU from January to December 2003 were enrolled in this study. This study evaluated the demographic variables, mortality, APACHE II score, comorbidity, antibiotics used, hospital and ICU stay, Clinical Pulmonary Infection Score, and mechanical ventilation. A retrospective analysis was made by a review of the patients' medical records. Results : Carbapenem sensitive and resistant A. baumannii was isolated from 23 patients and 26 patients respectively. Univariate analysis revealed renal disease, the use of carbapenem and aminoglycoside to be statistically significant factors for carbapenem resistance. Multivariate analysis revealed carbapenem use(p=0.024; OR, 8.17; CI 1.32 to 50.68) to be positively associated with carbapenem resistance, and aminoglycoside use(p=0.026; OR, 0.18; CI, 0.04 to 0.82) to be negatively associated with carbapenem resistance. There was no significant difference in mortality between the carbapenem sensitive and resistant group(30 vs 42%. P=0.39). Conclusion : The occurrence of carbapenem resistant A. baumannii is positively associated with carbapenem use and negatively associated with aminoglycoside use. Carbapenem resistance in the sputum culture did not affect the mortality rate.

• Childhood Kidney Diseases
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• v.17 no.1
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• pp.19-24
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• 2013

Purpose: Recently, enterococcus spp. have become one of the most common nosocomial pathogens with increasing rates of multi-drug resistance. However, study on enterococcal urinary tract infections (UTIs) in children is very limited, especially community acquired UTIs. We studied the clinical characteristics of enterococcus spp. in community acquired UTIs and antibiotic resistance within our urban area. Methods: All children with first episode of community acquired UTIs due to enterococcus spp. and Echerichia coli who were admitted in Pusan National University Children's Hospital between January 2010 and January 2013 were included in our study. We retrospectively reviewed their medical records. Results: During the study period, 201 patients were identified to have first episode of community acquired UTIs. 154 cases were E.coli UTIs (76.6%) and 11 cases were enterococcal UTIs (5.5%) and all enterococcus spp. were Enterococcus feacalis. In enterococcal UTI group, voiding cystourethrogram(VCUG) was performed in 7/11 patients and demonstrated 4 vesicoureteral refluxes (VURs) with renal scar and 3 patients underwent corrective surgery. In E.coli UTI group, VCUG was performed in 121/154 patients and demonstrated 23 VURs and 11 patients underwent corrective surgery. Enterococcal group had significant high rate of underlying urinary abnormalities and surgical corrections compared with E. coli group. All enterococcus spp. were susceptible to ampicillin, vancomycin and linezolid, but all were resistant to tetracycline. They also showed 71.4% resistance to trimethoprim-sulfamethoxazole and 20% resistance to ciprofloxacin. Conclusion: Community acquired enterococcal UTIs in children were rare within our urban area. However, they could be indicative of severe underlying urinary tract abnormalities.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.684-690
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• 2000

Background : The most common cause of treatment failure of pulmonary tuberculosis is early stoppage of treatment or irregular medication. The most important aspect of a retreatment is regular medication provided over a long period. Inadequate treatment may cause drug resistance and prolong the duration of chemotherapy. This study analyzed the risk factors of pulmonary tuberculosis patients, who failed in retreatment, and to use the results as basic data in the management of intractable tuberculosis patients with improving the rate of retreatment success. Methods : We performed a retroactive study of 62 pulmonary tuberculosis patients in retreatment at National Mokpo Tuberculosis Hospital from Jan. 1994 to Dec. 1995. The patients were separated into two groups: group I was retreatment failure and group II was retreatrnent success. For the analysis of risk factors in retreatment failure, we compared the difference between the two groups and tested the confidence limit about results of the results by independent t-test, ${\chi}^2$ test and Fisher's exact test. Results : The treatment failure rate of retreatment patients was 13(21%), and treatment success 49(79%). No significant difference (p>0.05)in age, sex, number of treatment, irregular rate of treatment, extent of the disease & cavitary lesion on the chest X-ray, number of resistance drugs, number of used drugs to medication, number of sensitive bactericidal drugs to medication, rate of sensitive drugs to medication and resisiance to INH & RFP had not significant difference. was found. However, the number of treatment was $2.4{\pm}0.8$ in group I and $1.6{\pm}0.9$ in group II, and had showing a significant difference(p<0.05) between the two groups. Conclusion : The risk factor of retreatment failure was more irregular previous treatment the irregularity of the previous treatment. For reducing the retreatment failure of pulmonary tuberculosis, greater efforts are needed more need to be done to prevent failure of first treatment.