• Clinical and Experimental Pediatrics
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• v.61 no.11
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• pp.366-370
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• 2018

Purpose: Tuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals. Methods: A 4-year-old child without Bacille Calmette-$Gu{\acute{e}}rin$ vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts. Results: We examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB. Conclusion: This is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.

• Pediatric Infection and Vaccine
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• v.23 no.2
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• pp.94-101
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• 2016

Purpose: This study aimed to describe the results of a contact investigation on health care workers after exposure to a house officer with smear-positive pulmonary tuberculosis (TB). Methods: Eighty nine out of 101 subjects who had close contact with the index patient agreed to be enrolled in the investigation. The first contact investigation was conducted approximately 30 days after the index patient's onset of symptoms, followed by the second investigation after 10 weeks. In both, clinical manifestations were studied, and chest X-ray and tuberculin skin test (TST)/QuantiFERON-TB Gold (QFT-G) in dual screening strategy were conducted. Results: The first TST resulted in positive in 34 subjects (38.2%). QFT-G was conducted on 16 subjects who tested positive in the first TST and aged under 36. Six of them (37.5%) were positive. The second TST was conducted on 41 subjects with negative results in the first TST. Seventeen (41.5%) were positive and among them, three (17.6%) showed positive QFT-G. None of the subjects were diagnosed with active TB. The probability of TB infection through contact with the index patient was 7.3% (3/41) in dual screening strategy while it was 41.5% (17/41) in TST strategy. Conclusions: This first hospital-setting contact investigation for tuberculosis in Korea revealed that latent tuberculosis infection (LTBI) rates vary depending on different diagnostic strategies. This indicates the need for systematic guidelines for diagnosing LTBI in health care workers who have professional exposure to TB.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.327-334
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• 2003

We evaluated the anti-arthritic effect of a new diet-supplement product containing red ginseng, glucosamine, shark cartilage, ascorbic acid and manganese chloride for the relieving arthritic symptoms. Anti-inflammatory activities of the aqueous extract of red ginseng (250 and 500 mg/kg), glucosamine (240 mg/kg) and shark cartilage (240 mg/kg) were tested individually on vascular permeability and carrageenan-induced paw edema. Glucosamine and shark cartilage showed the inhibition of vascular permeability by 29.6 and 32.9%, respectively. Red ginseng (500 mg/kg) and shark cartilage showed the inhibition of carrageenan-induced paw edema at 0.5, 1, 2 and 3 hr. The supplement (red ginseng mixture: RGM) composed of red ginseng (43.5%), glucosamine (25.0%), shark cartilage (25.0%), ascorbic acid (5.0%) and manganese chloride (1.5%) was prepared and its inhibitory activities including vascular permeability and carrageenan-induced paw edema were comparable to anti-inflammatory drugs such as diclofenac and ibuprofen. It was also tested on adjuvant-induced arthritis in rats as one of chronic arthritic tests and Randall-Selitto assay as an analgesic test. RGM showed the inhibition against the swelling of rat paws induced by Mycobacterium tuberculosis at a dose of 1,500 mg/kg. Determination of cytokines of the sera sampled from arthritis-induced animals indicated that RGM increased the levels of $interferon-{\gamma}$ and interleukin-6, representing the immunostimulatory effect by red ginseng. RGM treatment moderately reduced the production of NO in RAW 264.7 cells in a dose-dependent manner. Taken together, these results support that RGM can be applicable for the improvement of arthritic as a new diet-supplement.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.163-177
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• 2008

Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 ($fimA^-$), CW120 ($ppk^-$) and KS7 ($relA^-$) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-$1{\beta}$ and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon-$\gamma$-inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.

• Journal of Korean Medical Science
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• v.33 no.47
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• pp.292.1-292.10
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• 2018

Background: We investigated the incidence of active tuberculosis among patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) inhibitors, with or without latent tuberculosis infection (LTBI). Methods: The study was performed at a Korean tertiary referral center between January 2011 and June 2017. In total, 740 patients with IBD who underwent LTBI screening tests and were followed-up for ${\geq}1$ year after TNF inhibitor treatment initiation were enrolled. LTBI was detected on the basis of tuberculin skin test results, interferon-gamma release assay results, chest X-ray findings, and previous tuberculosis treatment history. The patients were classified into LTBI (n = 84) or non-LTBI (n = 656) group. The risk of developing tuberculosis in each group was assessed on the basis of standardized incidence ratio (SIR) and 95% confidence interval (CI) for active tuberculosis. Results: Mean patient age was 33.1 years, and patients with Crohn's disease were predominant (80.7%). Within 1 year after the initiation of TNF inhibitor treatment, 1 patient in the LTBI group (1/84; 1.2%) and 7 patients in the non-LTBI group (7/656; 1.1%) developed active tuberculosis. The overall 1-year incidence of tuberculosis among the patients was significantly higher than that among the general population (SIR, 14.0; 95% CI, 7.0-28.0), and SIR was not affected by LTBI status (LTBI group: 14.5, 95% CI, 2.0-102.6; non-LTBI group: 14.0, 95% CI, 6.7-29.4). Conclusion: Patients with IBD undergoing TNF inhibitor treatment showed a higher 1-year incidence of tuberculosis than the general population irrespective of LTBI status.

• Korean journal of aerospace and environmental medicine
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• v.31 no.3
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• pp.77-81
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• 2021

Purpose: The United States of America have pre-migration screening program are mandated through legislation. The one of purpose of this program is to prevent the importation of certain communicable diseases. Examinations of migration applicants are performed by panel physicians who are licensed physicians in the countries of origin that have agreements with the government departments of the country of destination to undertake this activity. In recent decades, the number of US migrants has increased, however COVID-19 impacted this trend of international migrants. The Aim of this study is to examine trends of US applicants and outcomes of tuberculosis and sexual transmitted infections (STIs) screening in South Korean applicants for US visa. Methods: A total of 4,442 applicants participated in US visa health check-up in 2016 to 2020. Results: The numbers of applicant for US visa in males and females was 1,814 and 2,628. The positive results in tuberculosis and STIs screening was noted with 0.66% in nontuberculous mycobacteria (NTM), 0.03% in tuberculosis, 0.03% in gonorrhea, 0.08% in syphilis, and 0.74% in chlamydia. The age groups of 2 to 14 years showed higher positive rate (13.89%) in tuberculin skin test (TST) tests compared to the rate of interferon gamma release assay (IGRA) tests (0.44%, P<0.001). The positive ratio of NTM and abnormal chest X-ray (CXR) which required sputum tests among the applicants over 15 years old has trends to increase with age. The age groups of over 70 years showed high positive rate in NTM and abnormal CXR (4.10%, 20.51%). However, ages 15 to 49 years groups showed 0.00% to 0.30% in NTM and 1.08% to 3.91% in abnormal CXR. In the study population, the positive rates of STIs were 0.03%, 0.08%, and 0.74% in gonorrhea, syphilis, and chlamydia, respectively. Among the participants who underwent sputum smears and cultures were just 1 case of active tuberculosis (0.03%) and 25 cases of NTM infection (0.66%). Conclusion: This study found that rate of positivity in tuberculosis and STIs screening among South Korean applicants for US visa in 2016 to 2020. Regarding tuberculosis, the positivity of CXR among the aged 15 to 59 years applicants was lower than that among over 60 years old. Among 2 to 14 years, positivity of IGRA was very low. And IGRA test can reduce effort of further evaluation compared to TST test in South Korea, so IGRA test among young adults can be useful. High positive rates in STI among young adult could result in high active sexuality, especially chlamydia infection is most common. Therefore Chlamydia polymerase chain reaction should be considered formal protocol among the Korean applicant for US visa.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

• Herbal Formula Science
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• v.20 no.2
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• pp.13-28
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• 2012

Objectives : The present study aimed to investigate the pharmacological activity of water and ethanol (EtOH) extracts from Socheongnyong-tang (SCNT) on inflammation and its related disease. Methods : The cells were treated with nontoxic concentrations of water and EtOH extract from SCNT in BEAS-2B, HaCaT, RAW 264.7 and 3T3-L1 cells. These cells were stimulated by tumor necrosis facter (TNF)-${\alpha}$, TNF-${\alpha}$/interferon (IFN)-${\gamma}$, and lipopolysaccharide (LPS), respectively. 3T3-L1 cells were differentiated by insulin. After incubation, supernatant were collected and biological indicator measured by enzyme-linked immunosorbent assay. Results : Our results indicate that the water and EtOH extract of SCNT significantly inhibited the production of regulated on activation normal T-cell expression and secreted (RANTES) by treatment of TNF-${\alpha}$ in BEAS-2B cell, and significantly reduced the production of RANTES and macrophage-derived chemokine increased by treatment of TNF-${\alpha}$/IFN-${\gamma}$ in HaCaT cell. Moreover, those extracts significantly decreased the activity of nitric oxide and prostaglandin $E_2$ in LPS-induced RAW 264.7, and significantly inhibited the increased activity of glycerol-3-phosphate dehydrogenase and expression of leptin induced by differentiation in 3T3-L1 cell. Conclusions : These results indicate that both water and EtOH extract of SCNT has powerful effects on inflammation and its related disease. Therefore, SCNT can be developed as a potential pharmacological agent related various diseases. Although the significant effects were observed in both SCNT water and EtOH extract, the EtOH extract was more effective on most experiments than its water extract. Taken together, these findings indicate that the SCNT EtOH extract may have more potential pharmacological agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.