• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.128-138
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• 2007

Backgrounds: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. Methods: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. Results: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 ($C{\rightarrow}T$) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation ($AAA{\rightarrow}AAC$) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. Conclusions: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.831-837
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• 1995

Background: We conducted a study to determine the factors associated with, patterns of, and proportion of cases of pulmonary tuberculosis with multiple drug-resistance at Kosin medical center in Pusan. Methods: We abstracted data from 141 patients, who had active pulmonary tuberculosis and report forms of drug susceptibility between 1986 and 1994, and related the previous treatment history, the extent of lung involvement and the presence of cavities on chest X-ray films to the drug resistance. Results: Overall, 59(41.8%) of the 141 cases of tuberculosis were resistant to at least one drug and 29(20.9%) of the 139 cases were resistant to isoniazid(INH) and rifampin(RIF). Among the 63 patients with previous tuberculosis therapy, 40(63.5%) had isolates that were drug-resistant and 24(38.1%) were multi-drug resistant. Among the 78 without previous therapy, 19(24.4%) had isolates that were drug-resistant and 5(7.5%) were multi-drug resistant. For all 141, resistance to INH was most common(39.0%) followed by RIF(21.6%), ethambutol(EMB, 16.3%), $\rho$- aminosalicylic acid(10.8%), streptomycin(SM, 8.7%), and pyrazinamide(PZA, 8.0%). INH, RIF and PZA resistances were independently associated with a history of previous tuberculosis therapy (odds ratio; 3.3, 7.2 and 10.8 respectively), and RIF and SM resistance were significantly high according to the extent of lung involvement on the chest films(odds ratio; 2.9 and 2.8 respectively). Conclusions: We conclude, (1) that all persons in whom pulmonary tuberculosis is diagnosed should initially receive at least four-drug therapy(INH, RIF, PZA, and EMB or SM), (2) that susceptibility testing be done in all culture-positive patient, and (3) that those with a history of previous tuberculosis therapy or those who have advanced pulmonary tuberculosis need very careful clinical and microbiological follow-up.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1234-1244
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• 1997

Background : Nowadays drug resistant tuberculosis is making problems in the treatment of pulmonary tuberculosis and its number is increasing. Several reasons for this are considered including irregular medication, poor drug compliance and wrong regimens. But there are treatment failure cases in spite of regular medication with short-term standard regimens. We reviewed clinical data of 50 patients to find out possible causes of this. Method : Subject of this study was 50 patients who failed in the primary treatment of pulmonary tuberculosis in spite of regular medication with short-term standard regimens. All of them were under treatment with secondary regimens in National Masan Tuberculosis Hospital on Oct 1996. The patient's records were analyzed retrospectively and direct interviews with patients were done. Results : There were relatively more patients in the age of 20th. Male overwhelmed in number. There were smoking in 22 patients and drinking in 24 patients during medication. 17(34%) patients had family history of tuberculosis. Public health center was the most common site for the initial diagnosis among medical institutes. 42 patients had subjective symptoms for pulmonary tuberculosis. 38 patients got sufficient explanation from medical institute about tuberculosis and medication courses. 24 patients had bilateral lesions on chest X-ray film and 43 patients had cavitary lesions. 29 patients had past history for pulmonary tuberculosis with regular medication. The results of drug sensitivity test showed resistance in 41 patients of whom we could get the results. Conclusion : Main cause of treatment failure of pulmonary tuberculosis in spite of regular medication with short-term standard regimens was drug resistance. Several factors were considered to be related to high prevalence of drug resistance, including age of 20th, male, family history for tuberculosis, bilateral lesions or remaining cavitary lesion on chest X-ray film.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1245-1255
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• 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
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• v.50 no.1
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• pp.94-105
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• 2001

Background : Examining the biological susceptibility of Mycobacterium tuberculosis to pyrazinamide (PZA) in vitro is very difficult as PZA is inactive under normal culture conditions. The biological susceptibility test, an enzyme assay for Pzase activity, and a genetic test for pncA gene mutations, were performed in order to predict PZA resistance. Methods : 28 cultured clinical isolates of Mycobacterium tuberculosis were tested. The biological susceptibility was performed by the absolute concentration method using Lowenstein-Jensen media. The PZase activity was tested by means of Wayne's method. A 710-bp region includes the entire open reading frame of pncA was amplified and sequenced. Results : All six strains with positive PZase activity exhibited no pncA mutations with one strain showing a false resistance in the biological susceptibility test. Among the 22 strains with no PZase activity, 21 exhibited showed pncA mutations. In the biological susceptibility test, 20 strains were resistant, and one was susceptible, and the other flied to test. The mutation types varied with ten missense, one silent and one nonsense mutation 1 slipped-strand mispairing, and 6 frameshift mutations. Three strains had an adenine to guanine mutation at position -11 upstream of the start codon. Conclusion : The mutation at the pncA promotor region is frequent at -11 upstream position. Automatic sequencing of pncA is a useful tool for rapid and accurate detection of PZA resistant M. tuberculosis, and for demonstrating the epidemiological relatedness of the PZA resistant M. tuberculosis strains.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.206-217
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• 1995

Background: In patients with obstructive sleep apnea syndrome(OSAS), there are several factors increasing upper airway resistance and there is a predisposition to compromised respiratory function during waking and sleep related to constitutional factors including a tendency to obesity. Several recent studies have suggested a possible relationship between sleep apnea(SA) and systemic hypertension. But the possible pathophysiologic link between SA and hypertension is still unclear. In this study, we have examined the relationship among age, body mass index(BMI), pulmonary function parameters and polysomnographic data in patients with OSAS. And also we tried to know the difference among these parameters between hypertensive OSAS and normotensive OSAS patients. Methods: Patients underwent a full night of polysomnography and measured pulmonary function during waking. OSAS was diagnosed if patients had more than 5 apneas per hour(apnea index, AI). A careful history of previously known or present hypertension was obtained from each patient, and patients with systolic blood pressure $\geq$ 160mmHg and/or diastolic blood pressure $\geq$ 95mmHg were classified as hypertensives. Results: The noctural nadir of arterial oxygen saturation($SaO_2$ nadir) was negatively related to AI and respiratory disturbance index(RDI), and the degree of noctural oxygen desaturation(DOD) was positively related to AI and RDI. BMI contributed to AI, RDI, $SaO_2$ nadir and DOD values. And also BMI contributed to $FEV_1,\;FEV_1/FVC$ and DLco values. There was a correlation between airway resistance(Raw) and AI, and there was a inverse correlation between DLco and DOD. But there was no difference among these parameters between hypertensive OSAS and normotensive OSAS patients. Conclusion: The obesity contributed to the compromised respiratory function and the severity of OSAS. AI and RDI were important factors in the severity of hypoxia during sleep. The measurement of pulmonary function parameters including Raw and DLco may be helpful in the prediction and assessment of OSAS patients. But we could not find clear difference between hypertensive and normotensive OSAS patients.

• Korean Journal of Medicinal Crop Science
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• v.17 no.2
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• pp.90-96
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• 2009

The objective of this study was to investigate the effect of crude ginseng total saponins (CGS) against airway inflammation (AI) and airway hyperresponsiveness (AH) induced by diesel exhaust particles (DEP) in mice. AI and AH were induced by the intratracheal instillation with 0.1 $mg/m{\ell}$ of DEP suspension once a week for 10 weeks combined with ovalbumin (OVA) sensitization. Mice were also treated orally with 75 $mg/m{\ell}$ of CGS, 5 days a week for 10 weeks. Oral CGS treatment decreased in the level of serum immunoglobulin (IgE) and histamine increased by DEP and OVA, and declined respiratory resistance. It also dropped an enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, and an increased T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that CGS may alleviate allergen-related AI and AH in mice and may play an important role in the modulation of asthmatic inflammation.

• Journal of Korean Medicine for Obesity Research
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• v.14 no.2
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• pp.55-62
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• 2014

Objective: The prevalence of metabolic syndrome and type 2 diabetes is increasing worldwide. Mitochondrial dysfunction is known to be involved in insulin resistance and obesity, researches have been increasing highly. Astragali Radix extract (ARE) or its main components have been shown to perform comparably to insulin by significantly reducing blood glucose levels in animal models however, the influence on mitochondrial dysfunction are not well understood. Methods: ARE (0.2, 0.5 and 1.0 mg/ml) or metformin (2.5 mM) were treated in C2C12 after 6 day-differentiation. The expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and phosphorylation AMPK, peroxisome proliferators-activated receptror ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$), nuclear respiratory factors 1 (NRF1), mitochondrial transcription factor (Tfam) and myosin heavy chain were detected with western blotting or polymerase chain reaction analysis. The morphological changes were also investigated. Results: ARE dose dependently increased phosphorylation of AMPK and respectively activated mRNA expressions of $PGC1{\alpha}$, NRF1 and Tfam which are mitochondrial biogenesis regulators. Furthermore, there were some morphologic differences of differentiated cells between ARE treatment and control. Conclusions: This study suggests that ARE has the potential to increase muscle mitochondrial function by activating AMPK and $PGC1{\alpha}$.

• Journal of Chest Surgery
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• v.18 no.1
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• pp.79-85
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• 1985

The effect of graded increments in positive end-expiratory pressure [PEEP] on hemodynamics required to ventilate 8 critically ill patients is reported. Acute respiratory insufficiency was a cause of death in only one patient of drug inoxication among the 8 patients studied. The cardiac output was not changed significantly after the increment of PEEP to the level of 20 cm H2O. The heart rate was increased significantly from 15 cm H2O PEEP [P<0.01] as compared to 0 cm H2O PEEP; and the stroke volume was decreased significantly from 15 cm H2O PEEP [P<0.05]. The blood pressure was not affected at any level of PEEP, but the pulmonary artery pressure was elevated significantly at 10 cm H2O PEEP [P<0.01]. The right ventricular transmural filling pressure was not affected at the level of 10 cm H2O PEEP, but from 15 cm H2O PEEP it was increased significantly. With the increment of PEEP, the left ventricular stroke work index was decreased slightly; and at 20 cm H2O PEEP, it was decreased significantly. The right ventricular stroke work index was increased only at 10 cm H2O PEEP. The systemic vascular resistance was decreased significantly from 15 cm H2O PEEP [P<0.01].

• Journal of Chest Surgery
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• v.20 no.3
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• pp.520-527
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• 1987

Clinical analysis was performed of 89 secundum type atrial septal defect patients operated on during the period from July, 15th, 1981 to March, 1987 in the Thoracic and Cardiovascular Surgery Department of Pusan National University Hospital. Secundum type ASD was 2`I.0% among all of congenital heart diseases operated in the same period. The age distribution of patients ranged from 3 to 41 years and sex ratio, male to female was 1.23 to 1.0. Common symptoms were exertional dyspnea 64.0%, frequent upper respiratory infection 43.8%, cyanosis 10.1% and fatigue 7.9%. The mean value of cardiac catheterization data of the group of ASD combined with another cardiovascular anomalies was compared with that of only ASD group. The amount of shunt showed not statistically significant difference between two groups [P>0.05] but pulmonary arterial pressure and pulmonary vascular resistance of combined group was significantly higher than that of only ASD group [P<0.02, P<0.01]. The difference of mean hemodynamic data between the age group below 20 years and above 21 years was not statistically significant [P>0.05]. All cases were operated under cardiopulmonary bypass. Among these 51 were closed directly and 38 were applied Dacron patch. Two most common associated cardiac anomalies were pulmonary stenosis [8 cases, 9.0%] and VSD [8 cases, 9.0%]. The most frequent postoperative complication was wound infection, One patient died of low cardiac output on 10th postoperative day and the overall operative mortality was 1.1%