• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.173-182
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• 2002

Background : Nontuberculous mycobacteria (NTM) have usually been considered to be contaminants of colonizers when isolated from respiratory specimens in Korea, where there is a high prevalence of tuberculosis and a low rate of HIV infections. Therefore, there has been few studies on the clinical significance of NTM species in immunocompetent patients were investigated. Methods : Thirty-five NTM isolates, for which species identification was requested by the treating physicians during 1999 at the Asan Medical Center, were retrospectively analyzed. They were identified to the species level by mycolic acid analysis using high-performance liquid chromatography. The medical records of the patients with the NTM isolates were reviewed to identify those patients who met the American Thoracic Society (ATS)'s criteria for mycobacterial pulmonary infection. Their antimicrobial susceptibility data were compared with the clinical outcomes. Results : The NTM were identified as M. intracellulare (6 isolates), M. avium (5), M. abscessus (5), M. gordonae (5), M. terrae complex (4), M. szulgai (2), M. kansasii (2), M. fortuitum (2), M. peregrinum (1), M. mucogenicum (1), M. celatum (1), and M. chelonae (1). All 35 patients showed clinical symptoms and signs of chronic lung disease, but none had a HIV infections; 16 (45.7%) patients were found to be compatible with a NTM pulmonary infection according to the ATS criteria, 5 and 4 cases were affected with M. intracellulare and M. abscessus, respectively; 8 patients had a history of pulmonary tuberculosis. 13 patients received antimycobacterial therapy for an average of 21 months and 9 patients were treated with second-line drugs. Only 4 patients had improved radiologically. Conclusion : A NTM should be considered a potential pathogen of pulmonary infections in immunocompetent patients with chronic pulmonary diseases. Most NTM infections were left untreated for a prolonged period and showed a poor outcome as a result, M. intracellulare and M. abscessus were the two most frequent causes of NTM pulmonary infections in this study. Species identification and antimycobacterial susceptibility tests based on the species are needed for the optimum management of a NTM pulmonary infection in patients.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.253-264
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• 2002

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was $56.43{\pm}9.41$ yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P<0.05). There was no association between p27 or uteroglobin expression and survival. Conclusion : The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.775-785
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• 1999

Background : The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods : 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. Results : Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methyprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion : These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.113-126
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• 2002

Background : DNA repair plays a crucial role in protection from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to lung cancer. The XPC gene contains 15 exons and encodes a 940 amino acid protein that plays a central role in DNA damage recognition of the nucleotide excision repair pathway, which is a major DNA repair mechanisim removing the bulky-helix distorting DNA lesions caused by smoking. Recently several polymorphisms in the XPC gene were identified. In addition, it is possible that these polymorphisms may affect the DNA repair capacity, which modulate cancer susceptibility. The relationship between codon 499 and 939 polymorphisms, and a poly(AT) insertion/deletion polymorphism in the XPC gene, and the lung cancer risk were investigated. Materials and Methods : The genotypes were determined using either PCR or PCR-RFLP analysis in 219 male lung cancer patients and 150 healthy males controls. Results : The frequencies of the genotypes (Val499Ala, PAT and Lys939Gln) among the cases were not significantly different from those of the controls. There was no significant associantion between these polymorphi는 and the lung cancer risk when the analyses were stratified according to age, smoking status and the pack-years of smoking. Moreover, the genotypes had no apparent relationship with any of the histological types of lung cancer. There was a linkage disequilibrium among the Val499Ala, PAT and Lys939Gln polymorphisms. The PAT polymorphism had a strong linkage disequilibrium with the Lys939Gln polymorphism (kappa value=0.87). The XPC haplotypes showed no significant association with the lung cancer risk. Conclusion : These results suggest that XPC Val499Ala, PAT and Lys939Gln polymorphisms are not major contributors to the individual lung cancer susceptibility in Koreans.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.33-42
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• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.414-421
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• 2008

Background: Recently, in addition to multi-drug resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) has become rapidly growing public health threat. This study examined the clinical differences between pulmonary TB patients with extensively drug resistance (XDR) and multi-drug resistance (MDR) at the National Medical Center in Korea in order to determine the clinical characteristics associated more with XDR-TB than MDR-TB. Methods: Patients who received a diagnosis of culture-confirmed pulmonary TB and a drug sensitivity test (DST) for anti-TB drugs at the National Medical Center between January 2000 and August 2007 were enrolled in this study. The patients were identified into the XDR-TB or MDR-TB group according to the DST results. The clinical characteristics were reviewed retrospectively from the medical records. Statistical analysis for the comparisons was performed using a ${\chi}^2$-test, independent samples t-test or binary logistic regression where appropriate. Results: A total 314 patients with culture-confirmed pulmonary TB were included. Among them, 18 patients (5.7%) had XDR-TB and 69 patients (22%) had MDR-TB excluding XDR-TB. A comparison of the clinical characteristics, revealed the XDR-TB group to have a higher frequency of a prior pulmonary resection for the treatment of TB (odds ratio [OR], 3.974; 95% confidence interval [CI], 1.052~15.011; P value 0.032) and longer average previous treatment duration with anti-TB drugs, including a treatment interruption period prior to the diagnosis of XDR, than the MDR-TB group (XDR-TB group, 72.67 months; MDR-TB group, 13.09 months; average treatment duration difference between two groups, 59.582 months; 95% CI, 31.743~87.420; P value, 0.000). In addition, a longer previous treatment duration with anti-TB drugs was significantly associated with XDR-TB (OR, 1.076; 95% CI, 1.038~1.117; P value, 0.000). A comparison of the other clinical characteristics revealed the XDR-TB group to have a higher frequency of male gender, diabetes mellitus (DM), age under 45, treatment interruption history, cavitations on simple chest radiograph and positive result of sputum AFB staining at the time of diagnosis of XDR. However, the association was not statistically significant. Conclusion: Pulmonary TB patients with XDR have a higher frequency of a prior pulmonary resection and longer previous treatment duration with anti-TB drugs than those with MDR. In addition, a longer previous treatment duration with anti-TB drugs is significantly associated with XDR-TB.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.27 no.12C
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• pp.1288-1298
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• 2002

To implement elliptic curve cryptosystem in GF(2$\^$m/) at high speed, a fast divider is required. Although bit-parallel architecture is well suited for high speed division operations, elliptic curve cryptosystem requires large m(at least 163) to support a sufficient security. In other words, since the bit-parallel architecture has an area complexity of 0(m$\^$m/), it is not suited for this application. In this paper, we propose a new serial-in serial-out systolic array for computing division operations in GF(2$\^$m/) using the standard basis representation. Based on a modified version of tile binary extended greatest common divisor algorithm, we obtain a new data dependence graph and design an efficient bit-serial systolic divider. The proposed divider has 0(m) time complexity and 0(m) area complexity. If input data come in continuously, the proposed divider can produce division results at a rate of one per m clock cycles, after an initial delay of 5m-2 cycles. Analysis shows that the proposed divider provides a significant reduction in both chip area and computational delay time compared to previously proposed systolic dividers with the same I/O format. Since the proposed divider can perform division operations at high speed with the reduced chip area, it is well suited for division circuit of elliptic curve cryptosystem. Furthermore, since the proposed architecture does not restrict the choice of irreducible polynomial, and has a unidirectional data flow and regularity, it provides a high flexibility and scalability with respect to the field size m.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.145-154
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• 2004

Purpose : To examine whether a synthetic bile acid derivatives (HS-1200) sensitizes the radiation-induced apoptosis in human breast cancer cells (MCF-7) and to investigate the underlying mechanism. Materials and Methods : Human breast cancer cells (MCF-7) in exponential growth phase were treated with HS-1200 for 24 hours at 37$^{\circ}C$ with 5$\%$ CO$_{2}$ in air atmosphere. After removal of HS-1200, cells were irradiated with 2$\~$8 Gy X-ray, and then cultured Ii drug-free media for 24-96 hours. The effect of radiation on the clonogenicity of MCF-7 cells was determined with clonogenic cell survival assay with 16$\mu$M of HS-1200. The induction of apoptosis was determined using agarose gel electrophoresis and Hoechst staining. The expression level of apoptosis-related molecules, such as PARP, Bax, Bcl-2, Bak and AIF, were assayed by Western blotting analysis with 40$\mu$M of HS-1200 combined with 8 Gy irradiation. To examine the cellular location of cytochrome c, bax and AIF immunofluorescent stainings were undertaken. Results : Treatment of MCF-7 cells with 40$\mu$M of HS-1200 combined with 8 Gy irradiation showed several changes associated with enhanced apoptosis by agarose gel electrophoresis and Hoechst staining. HS-1200 combined with 8 Gy irradiation treatment also enhanced production of PARP cleavage products and increased Bax/Bcl-2 ratio by Western blotting. Loss of mitochondrial membrane potential ($\Delta$$\psi$$_{m}$) and increased cytochrome c staining indicated that cytochrome c had been released from the mitochondria in HS-1200 treated cells. Conclusion : We demonstrated that combination treatment with a synthetic chenodeoxycholic acid derivative HS-1200 and irradiation enhanced radiation-induced apoptosis of human breast cancer cells (MCF-7). We suggest that the increased Bax/Bcl-2 ratio In HS-1200 co-treatment group underlies the increased radio sensitivity of MCF-7 cells. Further futures studies are remained elusive.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.32-42
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• 2005

Purpose : To evaluate the incidence of arm morbidity following breast cancer surgery including axillary dissection and to identify related factors. Materials and Methods : One hundred and fifty nine patients were studied using a self-report questionnaire and a clinical examination. Lymphedema, reduction of range of motion in shoulder joint and subjective symptoms (pain, impaired arm movement, numbness, stiffness) were evaluated. As related factors, demographic, oncologic characteristics and types of treatment were analysed. Results : The incidence of lymphedema ($\geqq$2 cm difference comparing to unaffected arm) was $6.3\%$, $10.7\%$, $22.5\%$ and $23.3\%$ at each 10 cm, 20 cm, 30 cm, and 40 cm from wrist. Reduction of range of motion in shoulder joint ($\geqq$ 20 degree difference comparing to unaffected arm) was noted In more than 1/3 patients for flexion, abduction and internal rotation. Especially the reduction of range of motion in internal rotation was severe ($>50\%$ reduction) in 1/3 patients. Approximately 50 to $60\%$ of patients complained impaired arm movement, numbness, stiffness and pain. Body mass index (BMI) was the significant risk factor for lymphedema. Conclusion : Lymphedema was present in 1/3 of patients and the common sites of edema were 30 cm 40 cm proximal from the wrist. Also most severe reduction of range of motion in shoulder joint was with internal rotation. There needs weight control for lymphedema because BMI was the significant risk factor for lymphedema. Also rehabilitation program for range of motion especially internal rotation In shoulder joint should be developed.

• Journal of the Korean Society for Marine Environment & Energy
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• v.9 no.4
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• pp.193-202
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• 2006

The Consultative Meeting of the Convention on the Prevention of Marine Pollution by Dumping of Wastes and other matter, 1972 (London Convention 1972) has requested to International Maritime Organization (IMO) Marine Environmental Protection Committee to collaborate and help clarify a boundary issue between International Convention for the Prevention of Pollution from Shops, 1973 as modified by the Protocol of 1978 (MARPOL) and the London Convention concerning 'dumping' versus 'discharges' during normal operations of ships in 2004, and subsequently established a Joint London Convention/MEPC Correspondence Group. The Contracting Parties to London Convention expressed their environmental concerns on the broad interpretation of the "cargo-associated wastes" by the States, which could be discharged by ships under MARPOL. Regulatory regimes for the cargo residues appear to vary among states. Some countries require fur ships to discharge their cargo wastes into the port reception facility and IMO also recommends doing so. This paper examines the related current national and international legal texts for the regulation of disposal of wastes from ships in order to analyze the current global concern on the marine pollution associated with waste discharge during operations of ships. In particular, we attempt to evaluate the likely marine environmental consequences arising from the disposal of cargo residue using an hypothetical case for the coal cargo residue among bulk cargos in this paper, since location, magnitude and frequency of the discharge of coal cargo residues into the sea adjacent to Korean Peninsula are not readily available. The cargo residues may be discharged to the sea according to MARPOL 73/78; however, its marine environmental consequences can be significant depending upon the characteristics and amounts of wastes to be discharged. Also the public tolerance of the environmental consequences would be widely different among nations. Multilateral environmental agreements, in general, more strictly apply their rules if there are other options to disposal at sea, i.e. port reception facility in this case. Therefore, port reception facilities for the wastes generated by ships are recommended to be further constructed in major national ports in order to reduce the risk of environmental damages during the operations of ships.