• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.449-458
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• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.31-42
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• 2005

Background : Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce $H_2O_2$ and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess $H_2O_2$, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. Methods : This study examined the effect of exogenous, excess $H_2O_2$ on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. Result : The addition of excess $H_2O_2$ to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the $H_2O_2$ treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated $H_2O_2$ treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. Conclusion : The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.71-79
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• 2003

Background : A bronchoalveolar lavage(BAL) is useful in diagnosing the etiology of bilateral pulmonary infiltrations, but may worsen the oxygenation and clinical status in severely hypoxemic patients. This study assessed the safety and efficacy of the continuous positive airway pressure(CPAP) using a conventional mechanical ventilator via a face mask as a tool for maintaining the oxygenation level during BAL. Methods : Seven consecutive patients with the bilateral pulmonary infiltrates and severe hypoxemia ($PaO_2/FIO_2$ ratio ${\leq}200$ on oxygen 10 L/min via mask with reservoir bag) were enrolled. The CPAP 5-6 $cmH_2O(F_IO_2\;1.0)$ was delivered through an inflatable face mask using a conventional mechanical ventilator. The CPAP began 10 min before starting the BAL and continued for 30 min after the procedure was completed. A bronchoscope was passed through a T-adapter and advanced through the mouth. BAL was performed using the conventional method. The vital signs, pulse oxymetry values, and arterial blood gases were monitored during the study. Results : (1) Median age was 56 years(male:female=4:3). (2) The baseline $PaO_2$ was $78{\pm}16mmHg$, which increased significantly to $269{\pm}116mmHg$(p=0.018) with CPAP. After the BAL, the $PaO_2$ did not decrease significantly but returned to the baseline level after the CPAP was discontinued. The $SpO_2$ showed a similar trend with the $PaO_2$ and did not decrease to below 90 % during the duration of the study. (3) The $PaCO_2$ increased and the pH decreased significantly after the BAL but returned to the baseline level within 30 min after the BAL. (5) No complications directly related to the BAL procedure were encountered. However, intubation was necessary in 3 patients(43 %) due to the progression of the underlying diseases. Conclusion : In severe hypoxemic patients, CPAP using a face mask and conventional mechanical ventilator during a BAL might allow minimal alterations in oxygenation and prevent subsequent respiratory failure.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.433-438
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• 2008

Background: Measurement of the maximum oxygen uptake in patients with chronic obstructive pulmonary disease (COPD) has been used to determine the intensity of exercise and to estimate the patient's response to treatment during pulmonary rehabilitation. However, cardiopulmonary exercise testing is not widely available in Korea. The 6-minute walk test (6MWT) is a simple method of measuring the exercise capacity of a patient. It also provides high reliability data and it reflects the fluctuation in one' s exercise capacity relatively well with using the standardized protocol. The prime objective of the present study is to develop a regression equation for estimating the peak oxygen uptake ($VO_2$) for men with moderate to very severe COPD from the results of a 6MWT. Methods: A total of 33 male patients with moderate to very severe COPD agreed to participate in this study. Pulmonary function testing, cardiopulmonary exercise testing and a 6MWT were performed on their first visits. The index of work ($6M_{work}$, 6-minute walk distance [6MWD]${\times}$body weight) was calculated for each patient. Those variables that were closely related to the peak $VO_2$ were identified through correlation analysis. With including such variables, the equation to predict the peak $VO_2$ was generated by the multiple linear regression method. Results: The peak $VO_2$ averaged $1,015{\pm}392ml/min$, and the mean 6MWD was $516{\pm}195$ meters. The $6M_{work}$ (r=.597) was better correlated to the peak $VO_2$ than the 6MWD (r=.415). The other variables highly correlated with the peak $VO_2$ were the $FEV_1$ (r=.742), DLco (r=.734) and FVC (r=.679). The derived prediction equation was $VO_2$ (ml/min)=($274.306{\times}FEV_1$)+($36.242{\times}DLco$)+($0.007{\times}6M_{work}$)-84.867. Conclusion: Under the circumstances when measurement of the peak $VO_2$ is not possible, we consider the 6MWT to be a simple alternative to measuring the peak $VO_2$. Of course, it is necessary to perform a trial on much larger scale to validate our prediction equation.

• Journal of Sasang Constitutional Medicine
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• v.8 no.1
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• pp.43-56
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• 1996

As considering a study of the So-um-In and So-yang-In desease, I know each of Extra-disease (表病) and Intra-disease (裏病). I takes serious view of the Extra-Intra-Um-Yang-Up-Down (表裏陰陽升降). I try to join costitutional disease to the parts of human body, which base on the theory on Sa-sang constituional Medicine. And I make some diagrams of them. They could be summerized as follows. 1.The Extra-qi (表氣) is four-viscera (四臟) and four back parts of hurman body (後四海). The Intra-qi (裏氣) is four-digestive organs (四腑) and four fore parts of human body (前四海). 2. It is important that Yang-qi (陽氣) go up at So-um-In Extra-disease (少陰人 表病) and Um-qi (陰氣) go down at So-yang-In Extra-disease (少陽人 表病). And It is important that Um-qi (陰氣) go down at So-um-In Intra-disease (少陰人 裏病) and Yang-qi of Large Intestine (大關局) go up at So-yang-In Intra-disese (少陽人 裏病). 3. Looking into the Extra-disease, ◈ Sin-Yang-Gon-Yiel (腎陽困熱) and Ha-Cho-Chuk-Hyel (下篇蓄血) of So-um-In disease are the disease that Yang-qi don't go up from the buttock. So-Yang-sang-Pung (少陽傷風) of So-yang-In disease is the disease that Um-qi don't go down from the upper back. ◈ Yui-Ga-Sil (胃家室) of So-um-In disease is the disease that Yang-qi don't go up from the lower abdomen Gyel-Hung (結胸) of So-yang-In disease is the disease that Um-qi don't go down from the thorax. ◈ Mang-Yang (亡陽) of So-um-In disease is the disease that Yang-qi don't go up from Intra-qi so it go out to the Extra-qi. Mang-Um (亡陰) of So-yang-In disease is the disease that Um-qi don't go down from the Extra-qi so it go into the Extra-qi. ◈ Dea-Jang-Pa-Han of So-um-In disease and Sim-Ha-Gyel-Hung (心下結胸) of So-yang-In desease are half of Extra-qi and Inrea-qi. 4. Looking into the Intra-disease, ◈ The Intra-disease of So-um-In is Tae-um symtom (太陰證) and So-um symtom (少陰證). The So-um symtom is more severe than Tae-um symtom because a cold wave of Large Intestine (大腸冷氣) involve a warm wave of Stomach (胃局). ◈ The Intra-disease of So-yang-In is not to go up Yang-qi of Large Intestine. Deficit of Yang-qi from Large Intestine which go up at Stomach is more sever than deficit of Yang-qi from Stomach which go up at extremes.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.193-204
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• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.233-243
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• 2000

Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.257-264
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• 2000

Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.231-238
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• 1994

Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.