• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.118-125
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• 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), but the genes associated with the host immune system can be attributed to the development of TB. The ITGB2 gene encodes the integrin beta 2 chain CD18 protein and is present on chromosome 21. The integrin beta 2 chain is an integrin expressed in leukocytes and plays a very important role in leukocyte maturation and attachment. ITGB2 plays an important role in the phagocytosis of MTB and the aggregation of leukocytes in MTB infections. This study examined the genetic polymorphisms of the ITGB2 gene between the TB case and normal control using Korean genomic and epidemiologic data. As a result, a statistically significant correlation was confirmed in 10 SNPs. The most significant SNP was rs113421921 (OR=0.69, CI: 0.53~0.90, $P=5.8{\times}10^{-3}$). In addition, rs173098, one of the significant 10 SNPs, is possibly located in a binding motif with the transcription factor cofactor p300, and can affect ITGB2 gene expression. These findings suggest that the pathogenesis of TB may be influenced by a range of genetic factors related to the immune function of the host, e.g., the reactions associated with the recruitment and attachment of leukocytes. The results of this study could be used to predict the infection control for tuberculosis in a patient-tailored manner.

• Safety and Health at Work
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• v.3 no.1
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• pp.77-83
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• 2012

Zoonoses represent a public health risk recently pointed out by the spreading of previously unknown human infectious diseases emerging from animal reservoirs such as severe acute respiratory syndrome and avian influenza caused by H5N1-virus. These outbreaks have shown that animal breeding activities can pose a significant public health risk. Until now, the risk of zoonoses has probably been underestimated, particularly in occupational settings. The emergence or re-emergence of bacterial (Mycobacterium bovis and Brucella spp) or viral (hepatitis E virus) infections shows that zoonoses should be considered as emerging risks in agricultural and animal breeding and should be addressed by specific preventive interventions. Close cooperation and interaction between veterinarians, occupational health physicians and public health operators is necessary, for a worldwide strategy to expand interdisciplinary collaborations and communications in all aspects of health care for humans, animals and the environment. This is what the One Health Approach was intended to be.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.369-377
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• 2018

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.41-58
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• 2003

Background : The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. Method : For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. Result : Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. Conclusion : The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.497-505
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• 2002

Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.385-391
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• 2005

Background : The incidence of nontuberculous mycobacterium (NTM) infections in Korea is increasing. This retrospective study was performed to examine the recovery rate of NTM from respiratory specimens as well as the isolated NTM colony characteristics, and to assess the clinical significance of a NTM isolation. Methods : The results of the respiratory specimens requested for an acid-fast bacilli (AFB) examination during 2002 at Asan Medical Center, along with the patients clinical characteristics were analyzed. Results : A total 26,820 respiratory specimens were requested for the acid-fast bacilli (AFB) smear and culture during the study period. The proportion of M. tuberculosis and NTM isolation was 5.7% and 2.2%, respectively. Among the AFB smear and culture positive specimens, 12.2% were found to be NTM. The scotochromogen showing a low colony count < 20, which appeared to be contaminants, were isolated in 31.8% of the 584 NTM isolates. Excluding the low-colony scotochromogens, the M. avium-intracellulare complex was the most common NTM isolates (42.1%), and was also the most common causative organism for NTM pulmonary diseases. 8.4% (23/275) and 17.8% (49/275) of patients with NTM isolates met the American and British Thoracic Society diagnostic criteria for NTM pulmonary disease, respectively. Conclusion : In case of a positive AFB-smear or culture result, the possibility of NTM being a causative organism should always be considered, even in Korea, which has an intermediate incidence of tuberculosis.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.225-232
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• 2021

This study sought to investigate the distribution, antimicrobial resistance rate, and bacterial co-infection frequency of non-tuberculous mycobacteria (NTM) in a single center in Incheon, South Korea. A total of 8,258 specimens submitted for tuberculosis (TB)/NTM real-time PCR tests during the years 2015 to 2020 were retrospectively reviewed. In total, 296 specimens (3.6%) were NTM positive, and the positivity increased from 2.5% (30/1,209) in 2015 to 3.8% (66/1,740) in 2020. Of 296 NTM specimens, 54.7% (162/296) were identified as the Mycobacterium avium complex (MAC) followed by the Mycobacterium abscessus complex (MABC) 20.9% (62/296), M. fortuitum 6.4% (19/296) and M. flavescens 3.4% (10/296). Of the NTM-positive specimens, 76.7% (227/296) were tested for drug resistance. The results showed multidrug-resistant NTM in 40.1% (91/227) and extensively drug-resistant NTM in 59.9% (136/227) of these specimens. Of the 145 isolates taken for bacterial culture, bacteria/fungi co-infection with NTM accounted for 43.4% (63/145), in which the most common bacterial species was Klebsiella pneumonia (23.8%, 15/63). This study is the first report on the distribution and antimicrobial resistance of NTM in Incheon. As the proportion of NTM infections increases, active treatment and thorough infection control are required for effective management.

• Journal of Microbiology and Biotechnology
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• v.19 no.3
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• pp.323-330
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• 2009

Nontuberculous mycobacteria (NTM) are a major cause of opportunistic infections in immunocompromised patients, making the reliable and rapid identification of NTM to the species level very important for the treatment of such patients. Therefore, this study evaluated the usefulness of the novel target genes tuf and tmRNA for the identification of NTM to the species level, using a PCRrestriction fragment length polymorphism analysis (PRA). A total of 44 reference strains and 17 clinical isolates of the genus Mycobacterium were used. The 741 bp or 744 bp tuf genes were amplified, restricted with two restriction enzymes (HaeIII/MboI), and sequenced. The tuf gene-PRA patterns were compared with those for the tmRNA (AvaII), hsp65 (HaeIII/HphI), rpoB (MspI/HaeIII), and 16S rRNA (HaeIII) genes. For the reference strains, the tuf gene-PRA yielded 43 HaeIII patterns, of which 35 (81.4%) showed unique patterns on the species level, whereas the tmRNA, hsp65, rpoB, and 16S rRNA-PRAs only showed 10 (23.3%), 32 (74.4%), 19 (44.2%), and 3 (7%) unique patterns after single digestion, respectively. The tuf gene-PRA produced a clear distinction between closely related NTM species, such as M. abscessus (557-84-58) and M. chelonae (477-84-80-58), and M. kansasii (141-136-80-63-58-54-51) and M. gastri (141-136-117-80-58-51). No difference was observed between the tuf-PRA patterns for the reference strains and clinical isolates. Thus, a diagnostic algorithm using a tuf gene-targeting PRA is a promising tool with more advantages than the previously used hsp65, rpoB, and 16S rRNA genes for the identification of NTM to the species level.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.475-482
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• 2009

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.353-356
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• 2006

Acute transverse myelitis (TM) is a neurological syndrome caused by inflammation of the spinal cord. TM is rare but is frequently caused by viral or bacterial infections. TM caused by tuberculosis (TB) is extremely rare and there are no reports of TM caused by multidrug-resistant TB (MDR-TB). We report a case of acute TM due to MDR-TB in a 40-year-old man. The patient had been diagnosed with pulmonary TB and was started on the first-line anti-TB treatment. However, the chest radiographic findings were aggravated and neurological symptoms such as weakness in both lower extremities, sensory changes, and voiding difficulty were newly developed. The T2-weighted magnetic resonance image of the spine showed diffusely increased signal intensity in the spinal cord, particularly at the lower cervical and upper thoracic levels, without any definite evidence of myeloradicular compression, which is consistent with a diagnosis of TM. A drug susceptibility test revealed MDR and second-line anti-TB drugs were prescribed. The chest radiographic findings showed improvement after treatment, the mycobacterial culture converted to negative, the MRI findings improved, and there was partial improvement in the low extremity weakness. The patient has been prescribing second-line anti-TB medications for 14 months.