• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.164-172
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• 1996

Background : Transforming growth factor-$\beta$(TGF-$\beta$) may play a role in a variety of fibroproliferative disorders including pulmonary fibrosis via the induction of extracellular matrix accumulation. TGF-$\beta$ not only stimulates extracellular matrix production, but also decreases matrix degradation. Interstial lung diseases have demonstrated marked expression of TGF-$\beta$. Methods : To evaluate the possible role of TGF-$\beta$ in human pulmonary fibrosis, by using neutralizing antibody of TGF-$\beta$ we investigated immunohistochemically the expression of TGF-$\beta$ in the formalin-fixed, paraffin-embedded tissue sections of the 5 normal cases for the control, and a couple of pieces of tissues taken out of 3 cases with idiopathic pulmonary fibrosis, 3 cases with ILD from bleomycin toxicity, 3 cases with ILD from sarcoidosis, and 3 cases with ILD from eosinophilic granuloma. Results : In the 5 normal cases for the control, the TGF-$\beta$ was expressed in bronchial and alveolar epithelial cells. Up-regulation of the TGF-$\beta$ expression was showed in the interstitial fibroblast cells of alveolar septa in 5 pieces and proliferated alveolar pneumocytes in 1 piece among 6 pieces tissues taken out of 3 cases with idiopathic pulmonary fibrosis. Also up-regulation of the TGF-$\beta$ expression was showed in alveolar lining pneumocytes, intra-alveolar mononuclear cells, and epithelioid cells in most of cases of ILD from bleomycin toxicity, sarcoidosis and eosinophilic granuloma. Conclusion : These findings suggest that up-regulation of the TGF-$\beta$are involved in pathogenesis of interstitial lung fibrosis from variety of causes.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.984-991
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• 1998

Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.838-845
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• 1995

The determination of ADA(adenosine deaminase) activity in pleural fluid is useful in differental diagnosis of pleural effusion. The conventional method of determining ADA activity used by Giusti was influenced by contamination of ammonia. Additionally, because Giusti's method was mannual method a determining the ADA activities in sample, was not easily automated. In 1993, Oosthuizen HM with collegues developed simple kinetic method for determining ADA activity. It was reliable and suiable method for automation. In this study, we have measured ADA activity in 162 patients with various pleural effusion by Hitachi 747 autoanalyser using the Oosthuizen kinetic method for the purpuse of determination of new diagnostic cut-off value for the tuberculous effusion and evaluation of the correlation between the conventional method and new automated method. This new method of an enzymatic reaction involves 2, 6-dichlorophenolindophenol dye(DICP), adenosine, xanthine oxidase(XO), and nucleoside phosphorylase(NP). The results were as follows: 1) The mean pleural ADA activity of the tuberculous effusion was $52.53{\pm}16.43\;U/L$ and significantly higher than that of other groups(p<0.001). If the diagnostic cut-off value of pleural ADA activity for tuberculous effusion is above 30 U/L, the sensitivity is 96% and the specificity is 90%. 2) The mean pleural to serum ADA activity ratio of the tuberculous effusion was $2.29{\pm}0.96$ and it was also significantly higher than that of other pleural groups(p<0.001). If the diagnostic cut-off value of pleural to serum ADA activity ratio is 1.5, the sensitivity is 80% and the specificity is 88% in the diagnosis of tuberculous pleural effusion. 3) The new kinetic method is correlates well to Giuisti's conventional method(r=0.971). In conclusion, the new kinetic method described is easily automated and seems to be suitable for the routine determination of ADA activity.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.574-582
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• 1997

Background : Normal humans meet the increased ventilatory need during exercise initially by the increase of tidal volume (TV) and later by the increase of respiratory frequency (Rf). And the inspiratory duty cycle (Ti/Ttot) is also increased more than 50% for the compensation of the decrease of respiratory cycle provoked by the increase of respiratory frequency. The patients with chronic airflow obstruction show rapid and shallow breathing pattern during exercise because of the decreased ventilatory capacity and the increased dead space ventilation. However, the studies about the change of inspiratory duty cycle are only a few and there is no literature about the relationship between the change of inspiratory duty cycle and the degree of airflow obstruction. Methods : The subjects were the twelve patients with chronic airflow obstruction (CAO) and ten normal people. The incremental exercise test was done. The increase of work load was 10 W in CAO group and 25 W in normal control group. The analysis of the results was done by the comparison of the parameters such as minute ventilation (VE), TV, Rf, physiologic dead space (Vd/Vt), and inspiratory duty cycle between the two groups. Each parameters were compared after transformation into % control duration base that means dividing the total exercise time into five fractions and % control duration data were obtained at rest, 20%, 40%, 60%, 80%, and max. Statistical analysis was done by repeated measure ANOVA using SAS program. Results : The changes of VE and TV were significantly different between two groups while the change of Rf was not significant. The decrease of Vd/Vt was significantly low in CAO group. Ti/Ttot was markedly increased from 38.4 + 3.0% at rest to 48.6 + 4.5% at max in normal control group while Ti/Ttot showed little change from 40.5 + 2.2% at rest to 42.6 + 3.5% at max. And the change of inspiratory duty cycle showed highly good correlation with the degree of airflow obstruction (FEV1%). (r=0.8151, p < 0.05). Conclusions : The increase of Ti/Ttot during exercise observed in normal humans is absent in the patients with CAO and the change of Ti/Ttot is well correlated with the degree of airflow obstruction.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.493-504
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• 1997

Background : Non-small cell lung cancer is one of the most frequent cause of death due to cancer in men, and its incidence among women is rapidly increasing. Although there has been a recent surge of interest in combined modality therapy for stageIII non-small cell lung cancer(NSCLC), the optimal treatment is still not well established. Thoracic irradiation has long been the gold standard for locally advanced unresectable NSCLC. However, although conventional radiotherapy(XRT) can palliate symptom and improve local control of disease, it has at most only a modest effect on survival. Recently, cisplatin(cis-diamminedichloroplatinum) has been reported to enhance the cell-killing effect of radiation For patients with unresectable NSCLC, cisplatin-based concurrent chemoradiotherapy(CCRT) had the advantage of therapeutic response over XRT alone and therapeutic side effect more commonly occurred in CCRT group in EORTC(European Organization for Research and Treatment of Cancer) and other trials. Objectives : We compared therapeutic response, compliance, and side effects between CCRT and XRT in patients with advanced NSCLC. Patients and Method : Thirty patients with biopsy-proven inoperable NSCLC were randomized to one of two treatment arms. Arm A consisted of XRT, radiotherapy for 4~6 weeks(1.8 Gy given 20~33 times, in five fractions a week), and arm B consisted of CCRT, radiotherapy for 2 weeks(3 Gy given to times, in five fractions a week), followed by 3 week rest period and then radiotherapy 2 more weeks(2.5 Gy given 10 times, in five fractions a week), combined with 6mg cisplatin per square meter, given daily before radiotherapy. We evaluate therapeutic response, compliance, change of performance status, side effects, and radiation pneumonitis by using the author's made scoring system. Results : There was no significant difference in therapeutic response and compliance. But there was a significantly lower laboratory complication and radiation pneumonitis in CCRT group (p < 0.05). There's significant negative correlation between stage and therapeutic response score in both groups(R=0.353, p < 0.05) In both groups, patients with squamous cell carcinoma had a tendency to higher therapeutic response score than those with adenocarcinoma. Conclusion : There was no difference between CCRT and XRT in respect to therapeutic response and compliance. But CCRT had a advantage of decreased side effects.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF -resistance in TNF-$\alpha$ cDNA transfected cancer cells would be. an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1285-1295
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• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.128-136
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• 2002

Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.137-144
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• 2002

Background: Hemoptysis is an often alarming presenting symptom and VEGF is a major regulator of both normal and abnormal angiogenesis, including many inflarrunatory diseases. In this report the clinical significance of the serum VEGF level in patients with hemoptysis was investigated. Methods: Thirty-two patients with hemoptysis were evaluated. The estimated amount of hemoptysis, etiology and serum VEGF level was examined at admission and bronchial angiography was performed in 22 patients. In order to objectify the neovascularization status, one point for the presence of the A-V shunt, hypervascularity, vascular tortuosity was designated for a total of 0-3 points. Results: Mean quantity of hemoptysis was $172.4{\pm}270.4ml$. The mean angiographic neovascularization score was $1.23{\pm}0.75$. The serum VEGF level correlated with the quantity of hemoptysis(r=0.524, p=0.002) and with the angiographic neovascularization score(r=0.441, p=0.04). Using the standard diagnostic criterion for massive hemoptysis, the serum VEGF level of patients with massive hemoptysis($642.4{\pm}545.6$ pg/ml, n=13) was found to be higher than that of patients with non-massive hemoptysis($394.6{\pm}225.8$ pg/ml, n=19) (p=0.069). Conclusion: Regardless of the etiology, the serum VEGF may contribute to abnormal neovascularization in patients with hemoptysis. Therefore, it is suggested that serum VEGF measurements may help in predicting a massive hemoptysis.