• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.2
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• pp.85-93
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• 2012

Purpose: Developmental delay is caused by very diverse etiologic diseases. Most chronic disorders has some influence on development. Chronic or acute disorders of CNS are main etiologic diseases of developmental delay. Up to now, over 60 diseases are included in organic acidopathies and most of them causes acute or chronic recurrent CNS damage and developmental delay. We have done this study to find out the importance of organic acidopathies causing developmental delay in Korean childhood and adolescent patients. Method: Retrograde analysis for 738 patients with developmental delay whose clinical informations are available and have done urine organic acid analysis for 5 years period, between Jan. 1st 2007 to Dec. 31th 2011. Statistical analysis was done with Student's t test using SPSS. Result: Out of 738 patients, 340 patients (46.1%) showed abnormalities on urine organic acid analysis. The most frequent disease was mitochondrial respiratory chain disorders (MRCD) (253, 34.3%), followed by ketolytic defects(39, 5.3%), 3-hydroxyisobutyric aciduria (26, 3.5%), glutaric aciduria type II (8, 1.1%), pyruvate dehydrogenase deficiency (3, 0.4%), 3-methylglutaric aciduria (2, 0.3%), glutaric aciduria type I (2, 0.3%), ethylmalonic aciduria (1, 0.15%), methylmalonic aciduria (1, 0.15%), HMG-CoA lyase deficiency (1, 0.15%), 3-methylcrotonylglycinuria (1, 0.15%), fatty acid oxidation disorders(1, 0.15%) and FAOD (1, 0.15%). Conclusion: Mitochondrial disorders are most frequent etiologic disease on all age group, followed by ketolytic defects and various organic acidopathies. The number and diversities of organic acidopathies emphasize meticulous evaluation of basic routine laboratory examinations and organic acid analysis with initial sample on every developmental patient.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.265-274
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• 2002

Background : Tumor associated antigens, which are produced specifically by tumor cells, are promising targets for the early diagnosis and immunotherapy. Among the tumor associated antigens, MAGE (a melanoma antigen), BAGE, GAGE, PRAME and NY-ESO were named as cancer/testis specific antigens they are detected exclusively in the testis or cancer cells If MAGE is easily detectable in the sputum, it would become a convenient method for diagnosing lung cancer. This study was undertaken to investigate MAGE expression in the induced sputum obtained from lung cancer patients. Materials and Methods : In 14 control patients and 30 lung cancer patients, the induced sputum was collected after inhaling 3% saline(5 cc) delivered by nebulizer for approximately 5 minutes after a mouth rinse and bronchodilator inhalation. The induced sputum was placed in a conservative-mixed solution (guanidinium isothiocyanate, Triton X-100). The total cellular mRNA was extracted from the cells and RT PCR and nested PCR were run in 30 and 35 cycles respectively, with two different types of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results : MAGE expression was not detected in the 14 controls, but in the 30 cancer patients, MAGE was found in 24 patients (80%, p=0.001). In the cancer patients, there were no differences in the expression level according to the tissue types (squamous cell cancer 13/17, adenocarcinoma 7/9, and small cell cancer 4/4, p-0.56). Among the 24 MAGE-positive patients, the tumor was not visible on a bronchoscopy in 11 patients (45.8%). Conclusion : A study of MAGE in induced sputum appears to be a useful and complementary method in the diagnosis of lung cancer. A further prospective study with more patients is recommended.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.213-221
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• 2001

Background : There is a well recognized interlaboratory variation in the results using the polymerase chain reaction(PCR) to detect the IS6110 sequence. The clinical utility of a commercially developed PCR test(Amplicor) in bronchial washings for detecting pulmonary tuberculosis in smear negative patients was evaluated. The sensitivity and specificity of Amplicor was compared with that of an in-house PCR test used for detecting the IS6110 sequence of Mycobacterium tuberculosis(M.tbc) in the bronchial washing fluid. Methods : 66 patients whose sputum smear for M. tbc were negative or who could not produce any sputum were recruited from January 1999 to July 1999. They all had a bronchoscopy performed to determine if there were signs of hemoptysis, patients who could not cough up sputum, lung lesion that exclude pulmonary tuberculosis. Pulmonary tuberculosis was diagnosed on the basis of a positive culture or a response to anti-tuberculosis therapy. Results : 19 patients with tuberculosis were identified and samples from 16 patients were later confirmed by culture. Bronchial washing for Amplicor PCR revealed a sensitivity, specificity, positive and negative predictive values of 94.7%, 97.9%, 94.7%, 97.9%, respectively. Using IS6110 based PCR, the sensitivity, specificity, positive and negative predictive values were of 73.7%, 87.2%, 70%, 89.1% respectively. Conclusion : Bronchial washing for Amplicor PCR proved to be more useful than IS6110 based PCR in rapidly diagnosing smear negative pulmonary pulmoary tuberculosis in patients where tuberculosis was likely to be differential and rapid diagnosis was essential for optimal treatment.

• Sleep Medicine and Psychophysiology
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• v.12 no.1
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• pp.32-38
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• 2005

Objectives: Obstructive sleep apnea syndrome (OSAS) has drawn increasing attention as medical community has become to be aware of its co-morbidities and complications, especially cardiovascular complications and excessive daytime sleepiness with accident proneness. As of now, polysomnography is the standard tool to diagnose sleep apnea and estimate the treatment validity. However, its being rather expensive and inconvenient, alternate diagnostic tools have been proposed including wrist actigraphy. So far, actigraphies have been adopted usefully to field-survey sleep apnea prevalence. In this study, we attempted in a sleep laboratory setting to assess the supplemental value of actigraphy in diagnosing OSAS. Methods: This study was done at the Division of Sleep Studies, the Seoul National University Hospital. Thirty-seven clinically suspected cases of OSAS underwent the one-night polysomnography, simultaneously wearing an actigraphy on non-dominant wrist. We analyzed the data of 27 polysomnographically-proven OSAS patients (male：female 20： 7；age $47.6{\pm}12.9$ years old；age range 23 to 72 years) with no other sleep disorders. We calculated RDI (respiratory disturbance index) from the polysomnography data and FI (fragmentation index) from the actigraphy data. Pearson correlation was calculated in order to compare FI with RDI and to evaluate the supplemental diagnostic value of the actigraphy. Results: Mean total sleep time on polysomnography was $401.4{\pm}57.8\;min$ (range of 274.0 to 514.1 min). Mean RDI was $21.7{\pm}20.4/hour$. Mean FI was $21.9{\pm}13.0/hour$. RDI and FI showed significant correlation (r=0.55, p<0.01). Conclusions: Wrist actigraphy in OSAS patients generates a comparable outcome to polysomnography, in measuring the nocturnal sleep fragmentation. The actigraphy could be used supplementally in inpatients, outpatients, and field survey subjects, if polysomnography is unavailable or impossible. In follow-ups related with nasal CPAP (continuous positive airway pressure), upper airway surgery, and oral appliance in OSAS patients, the actigraphy might play a more dominant role in the future.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.570-578
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• 2001

Background: With cases of chronic obstructive pulmonary disease(COPD), weight loss and low body weight have been found to correlate with increased mortality and poor prognosis. Therefore, nutritional aspects are an important part of the treatment in cases of COPD. In Korea, there is only limited data available for the changes of resting pulmonary function in relation to nutritional status. This study was carried out to investigate the differences of resting pulmonary function in relation to the nutritional status of patients with COPD. Method : 83 stable patients, with moderate to severe COPD, were clinically assessed for their nutritional status and resting pulmonary function. The patients' nutritional status was evaluated by body weight and fat-free mass (FFM), which was assessed by bioelectrical impedance analysis. According to their nutritional status, the 83 patients were divided into two groups, designated as the depleted, and non-depleted, groups. Result : Of the 83 patients, 31% were characterized by body weight loss and depletion of FFM, whereas 28% had either weight loss or depleted FFM. In the depleted group, significantly lower peak expiratory flow rate(p<0.05) and Kco(p<0.01), but significantly higher airway resistance(Raw, p<0.05) were noted. There was no difference for the non-depleted group in forced expiratory volume at one second, residual volume, inspiratory vital capacity, or total lung capacity. Maximal inspiratory pressure($P_{Imax}$) was also significantly lower in the depleted group(p<0.05). Conclusion : We conclude, from our clinical studies, that nutritional depletion is significantly associated with the change in resting pulmonary function for patients with moderate to severe COPD.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.614-623
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• 2000

Background : Diffuse alveolar hemorrhage (DAH) is rare but often fatal. To determine the clinical manifestations of DAH, its etiology, clinical course and prognosis were studied. Method : A retrospective analysis was performed in 21 patients that were diagnosed as DAH. Diagnosis of DAH was based on the presence of the "classical triad" of hemoptysis, anemia, and rapidly progressive infiltrates on chest X-ray and a finding of bronchoalveolar lavage or lung biopsy. Results : Thirteen patients (61.9%) had collagen vascular diseases (CVDs) as underlying disease and 10 patients had systemic lupus erythematosus. Females were more prevalent in CVD than in non-collagen vascular disease (NCVD). Otherwise, there were no significant differences between the two groups in terms of clinical manifestations. Dyspnea (95.2%), cough (76.2%), hemoptysis (61.9%), and fever (33.0%) were frequent symptoms. The initial creatinine level was higher in CVD than in NCVD ($3.27{\pm}3.15$ mg/dl vs. $1.19{\pm}0.94$ mg/dl, p=0.030). The corresponding drop in hemoglobin level was $2.69{\pm}1.26$ g/dl. Maximal drop in hemoglobin preceded the progression of infiltrates on the chest radiograph by $1.38{\pm}4.22$ days. The mortality rate was higher in the patients with NCVD than in those with CVD (50.0% vs. 23.1%). Conclusion : The DAH can occur not only in patients with CVD but also in those with NCVD. Higher creatinine level CVD in patients is associated with renal involvement in conjunction with DAH. The maximal drop in hemoglobin preceeding the progression of infiltrates on the chest radiograph suggests that the drop in hemoglobin is important for diagnosing DAH.

• Korean Journal of Biological Psychiatry
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• v.14 no.2
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• pp.115-121
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• 2007

Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

• Progress in Medical Physics
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• v.24 no.4
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• pp.253-258
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• 2013

The purpose of this study is to evaluate and analyze the relationship between the external radiation dose reconstruction which is transmitted from the patient who receives radiation treatment through electronic portal imaging device (EPID) and the internal dose derived from the Monte Carlo simulation. As a comparative analysis of the two cases, it is performed to provide a basic indicator for similar studies. The geometric information of the experiment and that of the radiation source were entered into Monte Carlo n-particle (MCNPX) which is the computer simulation tool and to derive the EPID images, a tally card in MCNPX was used for visualizing and the imaging of the dose information. We set to source to surface distance (SSD) 100 cm for internal measurement and EPID. And the water phantom was set to be 100 cm of the source to surface distance (SSD) for the internal measurement and EPID was set to 90 cm of SSD which is 10 cm below. The internal dose was collected from the water phantom by using mesh tally function in MCNPX, accumulated dose data was acquired by four-portal beam exposures. At the same time, after getting the dose which had been passed through water phantom, dose reconstruction was performed using back-projection method. In order to analyze about two cases, we compared the penetrated dose by calibration of itself with the absorbed one. We also evaluated the reconstructed dose using EPID and partially accumulated (overlapped) dose in water phantom by four-portal beam exposures. The sum dose data of two cases were calculated as each 3.4580 MeV/g (absorbed dose in water) and 3.4354 MeV/g (EPID reconstruction). The result of sum dose match from two cases shows good agreement with 0.6536% dose error.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.177-184
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• 1993

Background: Accurate staging of bronchogenic carcinoma is important in determining resectability and metastasis of tumor to the subcarinal nodes is generally believed to indicate poor prognosis. The technique of Transbronchial needle aspiration (TBNA) has offered a safe & effective way to asscess mediastinal lymph node involvement in the staging of lung cancer. We performed TBNA in patients who were suspected lung cancer to evaluate the clinical usefulness of the TBNA. Method: TBNA of the subcarinal lymph node was performed at the time of initial diagnostic bronchoscopy in 60 patients with suspected lung cancer, and 42 cases of histologically proved bronchogenic cancer were analized. Results: The frequency of adequate samples by transbronchial needle aspiration (TBNA) was 81% and the positive rate of malignant cells by TBNA was 14.7%. There were no differences in positive rates by tumor cell types. In patients with thickened carina on bronchoscopy, the TBNA was positive in 33.3% as compared to 5.3% of normal carina on bronchoscopy, and the difference was statistically significant (p<0.05). In patients with enlarged subcarinal lymph node on chest CT, the positive rate of malignant cells (50.0%) was higher than that of normal sized subcarinal lymph node on chest CT (4.8%) (p<0.01). There were no specific complications in the TBNA procedure. Conclusion: TBNA is a relatively safe procedure and it offers the possibility of avoiding the cost and morbidity of surgical staging in patients especially whose carina is thickened on bronchoscopy and whose subcarinal LN was enlarged on chest CT.