• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.432-440
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• 2000

Background : The prevalence of pulmonary tuberculosis among the elderly is increasing in Korea and in the developed countries due to the increased elderly population and their predispositions to chronic disease, poverty and decreased immunity. To define the characteristics of pulmonary tuberculosis in the elderly, we evaluated the clinical spectrum of pulmonary tuberculosis. Method : We analyzed 92 patients retrospectively that were diagnosed as active pulmonary tuberculosis over the age of 65. The analysis involved patient's profiles, clinical manifestations, coexisting diseases, diagnostic methods, anti-TB medications and their side effects, and treatment outcomes. Results : The results were as follows : - 1) The ratio of male to female was 2.1:1(62:30 cases) 2) Chief complaints were a cough (47.8%), dyspnea (40.2%), sputum (38.0%), chest pain (12.0%), anorexia (10.9%), and fever (9.8%). 3) 38 (41.3%) of cases had a past history of pulmonary tuberculosis. 4) The coexisting diseases were : -COPD, 25 cases (27.2%); pneumonia, 17 cases (18.5%); DM. 13 cases (14.1%); and malignancy, 10 cases (10.9%). 5) The positivity of Mantoux test (5 TU, PPD-S) was 82.7%. 6) Pulmonary tuberculosis was diagnosed using the following methods : sputum AFB (Acid Fast Bacillus) smear 42.4%, sputum TB (M. Tuberculosis) culture 15.2%, sputum TB PCR (Polymerase Chain Reaction) 10.9%, bronchial washing AFB smear 2.1%, chest radiology only 25.0%. 7) Locations of radiologic lesions were RULF, 50 cases; RLLF, 50 cases, mostly, then LLLF ; 26 cases were leastly involved. 8) The coexisting tuberculosis were endobronchial TB(8.7%), TB pleurisy(7.6%) miliary TB(5.4%), intestinal TB(2.2%), renal TB(1.1%) 9) The proportion of treatment regimen with 1st line drug and 2nd line drug were 92.3% and 7.6%, respectively. 10) The outcome of treatment were as follows : cured 31.5%, expired 13.0%, no return 47.8%, follow-up now 7.6%. Conclusion : The pulmonary tuberculosis in the elderly has atypical patterns with chronic coexisting diseases. Therefore, the possibility of pulmonary tuberculosis should be considered in elderly patients with pulmonary symptoms.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.110-115
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• 2009

Background: A forceps-biopsy is performed to acquire tissue from patients with an endobronchial carcinoma using a flexible bronchoscope. Recently, a cryo-biopsy has also been used to acquire tissue samples. Cryo-biopsy is the diagnostic application of extreme cold for the local destruction of abnormal living tissue. This technique is safe, with no radiation danger, no risk of electrical accidents, and a little risk of bleeding. This study compared a forceps-biopsy with a cryo-biopsy using a flexible bronchoscope, and examined the chemosensitivity and level of VEGF (vascular endothelial growth factor) in the specimens obtained from the cryo-biopsy. Methods: We present a prospective study of 30 consecutive patients who underwent a forceps-biopsy between January 2007 and October 2007 with a mean age of 62.1 years and a male:female ratio of 5 : 1. A flexible bronchoscope was inserted to the area of the abnormal lesions, and a cryo-probe was then applied through the working channel of the flexible bronchoscope. A temperature of approximately -h80 was delivered to the tumor site for 8 seconds. The cryo-biopsy was performed after destroying the tumor mass. Results: The mean size of the tissue from the forceps-biopsy and cryo-biopsy were 2.0${\pm}$1.2 mm and 6.0${\pm}$3.0 mm. A chemosensitivity test was performed on 5 specimens obtained using cryo-biopsy and the level of VEGF was examined in 2 specimens obtained from a cryo-biopsy. There were no side effects in either group. Conclusion: Cryo-biopsy using a flexible bronchoscope is a safe and effective technique for acquiring tissue samples.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.104-109
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• 2009

Background: Anemia is quite common in lung cancer patients and known to decrease the quality of life. Darbepoetin alfa is an erythropoiesis-stimulating protein approved for administration to cancer patients. This study examined the efficacy and safety of darbepoetin alfa in lung cancer patients with a hemoglobin concentration <10 g/dl during chemotherapy. Methods: Lung cancer patients (n=178) received darbepoetin alfa at doses of 1.91 ${\mu}g/kg$ per week until the hemoglobin concentration increased to >10 g/dl. The efficacy and safety were measured by comparing the hemoglobin concentration and assessing the adverse events. Results: After chemotherapy, the hemoglobin concentration decreased to 9.03${\pm}$0.64 g/dl. With the darbepoetin alfa treatment, the hemoglobin concentration increased to 10.09${\pm}$1.17 g/dl after 4 weeks reaching a peak hemoglobin concentration of 10.45${\pm}$1.18 g/dl. The changes in hemoglobin after 4 and 8 weeks with treatment were 1.08${\pm}$1.24 g/dl and 1.38${\pm}$1.59 g/dl (p<0.01). At least a 1 g/dl or more increase in hemoglobin was observed in 62.4% of patients. There were no serious adverse effects except for some mild reactions. Conclusion: Darbepoetin alfa administered to lung cancer patients appears to be an effective, well-tolerated treatment for chemotherapy induced anemia.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.6
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• pp.920-926
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• 1998

To investigate the effects of yellow loess on the microbial community after applying into C. polykrikoides as a red tide centrol method during decomposition process, we conducted this study using microcosm experiments, which consisted of sediment collected from Jinhae and Masan bay. The composition, number of bacteria and respiratory electron transport system activity (ETSA) were analyzed. The number of heterotrophic bacteria examined in the samples of both stations reached maximum value within 12 hrs with $10^7$ cells/dry g, independent with the yellow loess applied. In addition, a differenee in the variation of heterotrophic bacterial composition was not observed by adding the yellow loess, and Vibrio spp. always appeared during the culture periods, However, in day 8 culture, the sulfate reducing bacteria was $3.8\times10^7$ cells/dry g in Masan bay and $5.5\times10^6$ cells/dry g in Jinhae bay samples without yellow loess, and these were 120, 350 fold-and 160, 420 fold-increased when yellow loess was added (1 : 1, 1 : 2). The average ETSA was 6.8$\~$7.6 $\mu$g formazan $h^{-1}$ dry $g^{-1}$ independently with yellow loess in aerobic condition for both samples, but activity was decreased by addition of yellow loess in anaerobic. Thus the addition of yellow loess to marine sediment seems to have an effect to inhibit the anaerobic decomposition process and growth of sulfate reducing bacteria which lead to the bad condition of marine environments.

• Journal of Oral Medicine and Pain
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• v.33 no.4
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• pp.305-316
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• 2008

The mandibular advancement device(MAD) has been used to help manage snoring and obstructive sleep apnea. The aims of this study were to specify the demographic and clinical characteristics of the patients receiving long-term treatment with MAD and to quantify the compliance with and side effects of the use of the device. Of 103 patients who were treated with MAD for at least one full year after delivery date, 49 were able to be contacted with telephone and complete follow-up questionnaires were obtainable. They were telephoned to determine whether they were still using the device. If not, they were asked when and why they stopped using it. Patients were also asked how much effectiveness of the MAD in decreasing snoring and how much they and their bed-partners were satisfied with the MAD therapy. The initial respiratory disturbance indices and pre-treatment snoring frequency and intensity were obtained from the medical records of initial visit. All the data were compared between users and nonusers. The results were as follows: 1. Of 49 patients 25 are still using the device, but 24 stopped using it. Among nonusers nobody stopped wearing the device within first 1 month, but 37.5% of nonusers stopped wearing it in the following 6 months, and another 4.2% before the end of the first year. 2. The one-year compliance of the MAD therapy was 79.59%. 3. There were no significant differences in mean age, mean body mass index, and gender distribution between users group and nonusers group. 4. There was no significant difference in mean respiratory disturbance index at initial visit between users group and nonusers group. 5. There was no significant difference in pre-treatment snoring frequency and intensity between users group and nonusers group. 6. The degree of decrease in snoring with use of MAD was significantly higher in the users when compared to nonusers. 7. Patient's overall satisfaction with treatment outcome was significantly higher in the users when compared to nonusers. 8. Bed partner's satisfaction with treatment outcome tended to be higher in the users when compared to nonusers. 9. The most frequent reasons why patients discontinued wearing the MAD were: jaw pain(25%), dental pain(20.83%), broken appliance(20.83%), hassle using(16.67%), lost weight(8.3%), dental work(8.3%), no or little effect(4.17%), sleep disturbance(4.27).

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.275-284
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• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.481-488
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• 1999

Background: The routine application of the combined regimen of corticosteroid-antituberculosis therapy to the tuberculous pleurisy remains controversial. Steroid therapy to tuberculous pleurisy could be effective on the acceleration of absorption of pleural effusion and symptom improvement, but there has been debate about the effect of prednisolone on the prevention of pleural adhesion. So we studied the efficacy of combined regimen of prednisolone-antituberculosis therapy on the absorption of pleural effusion and prevention of pleural adhesion. Method: A prospective, randomized study was performed in 82 patients, 50 patients(non-steroid group) were treated with only antituberculosis regimen for 6 months and in 32 patients(steroid group) prednisolone(30mg/day) were administered in addition to antituberculosis regimen for one months and tapered for another month. The amount of pleural effusion was compared at the beginning of treatment, 2nd month, 6th month and final visit with chest X-ray findings which were graded from grade 0(complete absorption) to grade 6(near total haziness). Results: The amount of pleural effusion of steroid group at 2nd month, 6th month and final visit was lesser than that of non-steroid group(P<0.05). The incidence of the complete absorption of the pleural effusion was 3/32(9.4%) in steroid group, 1/50(2%) in non-steroid group at 2nd month after treatment; and 12/32(37.5%) in steroid group, 6/50(12%) in non-steroid group at 6th month after treatment(P<0.05). At final observation, the incidence of residual pleural thickening was 15/32(47%) in steroid group and 37/50(74%) in non-steroid group(P<0.05). No serious side effects were noted during the treatment with prednisolone. Conclusion: The administration of prednisolone in conjunction with antituberculosis chemotherapy improved the absorption of pleural effusion and decreased the residual pleural thickening.