• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.470-478
• /
• 1997

Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.493-504
• /
• 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
• /
• v.44 no.6
• /
• pp.1353-1365
• /
• 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
• /
• v.44 no.6
• /
• pp.1245-1255
• /
• 1997

Background : Rifampicin(RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant(MDR) tuberculosis. RPoB gene encodes the $\beta$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And rpoB gene mutations are the cause of RFP resistance of M. tuberculosis. Although several reports showed that PCR-SSCP would be a rapid diagnostic method for identifying the RFP resistance, there were few reports Performed using direct, clinical specimens. So we Performed PCR-SSCP analysis of rpoB gene of M. tuberculosis in direct, clinical specimens. Methods : 75 clinical specimens were collected from patients at Asan Medical Center from June to August 1996. After PCR of IS 6110 fragments, 43 both AFB smear-positive and IS6110 fragment PCR-positive specimens were evaluated. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. DNA was extracted by bead beater method. And heminested PCR was done using 0.1ul(1uCi) [$\alpha-^{32}P$]-dCTP. SSCP analysis was done using non-denaturating MDE gel electrophoresis. Results : The results of PCR of IS6110 fragments of M. tuberculosis were positive in 55(73%) cases of 75 AFB smear-positive clinical specimens. Of the 55 specimens, RFP susceptibility was confirmed in only 43 specimens. Of the 43 AFB smear-positive and IS6110 fragment-positive specimens, 29 were RFP susceptible and 14 were RFP resistant. All the RFP susceptible 29 strains showed the same mobility compared with that of RFP sensitive H37Rv in SSCP analysis of ropB gene. And all the other RFP resistant 13 strains showed the different mobility. In other words they showed 100% identical results between PCR-SSCP analysis and traditional susceptibility test. Conclusion : The PCR-sseP analysis of rpoB gene in direct clinical specimens could be used as a rapid diagnostic method for detecting RFP resistant M. tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.6
• /
• pp.774-779
• /
• 2000

Pseudomembranous colitis, although uncommon, is an important complication of antibiotics that is related to a variety of deleterious effects on the gastrointestinal tract. Rifampicin is one of the 1st line agents in the treatment of tuberculosis and a large number of patients are exposed to its potential adverse effects. We report upon a patient that had diarrhea due to pseudomembranous colitis after receiving antitubeculous medication, and which was probably caused by rifampicin. A 77-year-old man was admitted with diarrhea of three weeks duration. One month previously, he suffered from left pleuritic chest pain and left pleural effusion was noticed at chest X-ray. One week prior to the onset of diarrhea, he was started on empirically isoniazid, rifampicin, ethambutol and pyrazynamide as antituberculous medication. On admission, he complained of diarrhea, left pleuritic chest pain, dyspnea and sputum. On physical examination, breathing sound was decreased in the left lower lung field and bowel sound increased. Pleural biopsy revealed chronic granulomatous inflammation, which was compatible with tuberculosis, Sigmoidoscopy showed whitish to yellowish pseudomembrane with intervening normal mucosa, and his stool was positive for C.difficle toxin. He was diagnosed as pseudomembranous colitis and treated with oral metronidazole and vancomycin. The diarrhea did not recur after reinstitution of the anti-tuberculous medication without rifampicin inpatients with severe diarrhea receiving anti-tuberculous medication, rifampicin induced pseudomembranous colitis should be excluded.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.2
• /
• pp.271-279
• /
• 1998

Background: Diagnosis by direct microscopy and/or by culture of the Mycobacterium tuberculosis from body fluids or biopsy specimens is "Gold standard". However, the sensitivity of direct microscopy after Ziehl-Neelsen staining is relatively low and culture of mycobacteria is time consuming. Detection of mycobacterial DNA in clinical samples by the polymerase chain reaction is highly sensitive but laborious and expensive. Therefore, rapid, sensitive and readily applicable new tests need to be developed. So we had evaluated the clinical significance of serologic detection of antibody to 38 kDa antigen, which is known as the most specific to the M. tuberculosis complex, and culture filtrate antigen by ELISA in sputum AFB smear negative patients. Method: In this study, culture tests for acid fast bacilli with sputa or bronchial washing fluids of 183 consecutive patients who were negative of sputum AFB smear were performed. Simultaneously serum antibodies to 38 kDa antigen and unheated culture filtrate of M. tuberculosis were detected by an ELISA method. Results: The optical densities of ELISA test with 38 kDa and culture filtrate antigen were significantly higher in active pulmonary tuberculosis cases than in non tuberculous pulmonary diseases (p<0.05), but in patients with active pulmonary tuberculosis, those of the sputum culture positive patients for M. tuberculosis were not significantly different from those of the sputum culture negative cases(p>0.05). In the smear-negative active pulmonary tuberculosis patients, the sensitivity of the ELISA using 38 kDa antigen and culture filtrate was 20.0% and 31.4%. respectively. The specificity was 95.3% and 93.9%. respectively. Conclusion : In active pulmonary tuberculosis but smear negative, the serologic detection of antibody to 38 kDa antigen and culture filtrate by ELISA cannot substitute traditional diagnostic tests and does not have clinically significant role to differenciate the patient with active pulmonary tuberculosis from other with non-tuberculous pulmonary diseases.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.2
• /
• pp.128-136
• /
• 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
• /
• v.52 no.2
• /
• pp.137-144
• /
• 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.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.1
• /
• pp.5-13
• /
• 2002

Background: DNA repair plays a crucial role in protecting the genome from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to cancer. The human OGG1 (hOGG1) gene encodes DNA glycosylase/apurinic lyase and excise 8-hydroxyguanine, one of the major premutagenic DNA lesions, which is produced by oxygen radical forming agents including smoking. Recently several polymorphisms in the hOGG1 gene were identified, and it is possible that these polymorphism') may affect the DNA repair capacity and thus modulate cancer susceptibility. The relationship between the codon 326 polymorphism (Ser to Cys) in the hOGG1 gene and lung cancer risk was investigated. Materials and Method: The Ser326Cys genotypes were determined using PCR-RFLP analysis in 299 primary lung cancer patients and 186 healthy controls who were frequency (case:control=3:2) matched according to age and sex. Result: The frequencies of the Ser326Cys genotypes (Ser/Ser, Ser/Cys and Cys/Cys) among cases (23.4%, 51.8%, and 24.7%, respectively) were not significantly different from those among the controls (22.6%,52.1% and 25.3%, respectively). When the analyses were stratified according to age, sex, smoking status and packyears of smoking, no significant association between this polymorphism and lung cancer risk was found. Moreover, the Ser326Cys genotype showed no apparent relationship with any of the histological types of lung cancer. Conclusion: These result suggest that the hOGG1 Ser326Cys polymorphism is not a major contributor to individual lung cancer susceptibility in Koreans.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.1
• /
• pp.37-45
• /
• 2002

Background: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease that presents as coughing, copious sputum, exertional dyspnea, which progresses to bronchiectasis. The pathogenesis of bronchiectasis is controlled by inflammatory mediators, which are closely related to mucus hypersecretion, goblet cell dysplasia. In recent studies, the epidermal growth factor receptor(EGFR) system was reported to be associated with this process. It was hypothesized that a relationship exists between goblet cell dysplasia, EGFR expression, and inflammatory mediators produced by neutrophil. Method: Alcian blue/periodic acid -Schiff(AB/PAS) stain, MUC5AC, EGFR, CD16 immunohistochemical stain were examined to investigate a role for the EGFR system in a mucus hypersecretion in DPB using the lung biopsy specimens from 13 DPB patients and 6 controls. Results : In the DPB group, the AB/PAS and MUC5AC -stained areas were $8.31{\pm}3.36%$, $11.46{\pm}4.68%$, respectively. In the control group, the AB/PAS- and MUC5AC-stained areas were $50.5{\pm}5.77%$, $53.3%{\pm}6.67%$, which was significantly larger than in the DPB group (each comparison, p<0.05). The percentage of EGFR expression was $9.54{\pm}4.95%$ in the DPB group, but zero in of the control group. The extent of neutrophilic infiltration was $71.92{\pm}3.71$/5HPF in the DPB group and $45.0{\pm}5.73$/5HPF in the control group, which was statistically significant(p=0.002). Conclusion: The EGFR system is highly related to goblet cell dysplasia, mucus hypersecretion and neutrophilic inflammation in DPB.