• Molecules and Cells
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• v.38 no.10
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• pp.886-894
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• 2015

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

• Tuberculosis and Respiratory Diseases
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• v.70 no.4
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• pp.347-351
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• 2011

We report here an unusual case of pericardial tuberculoma that was misdiagnosed as thymic carcinoma on an imaging study. A 48-year-old woman was referred for evaluation of an anterior mediastinal mass. Computed tomography (CT) scans of the chest displayed cystic masses mimicking thymic carcinoma at the anterior mediastinum. Pericardiotomy and surgical drainage of the cystic masses were done, and pathologic examination of the excised pericardial specimen showed a chronic granulomatous inflammation with necrosis, compatible with tuberculosis. Acid-fast bacilli were also identified in the specimen. After treatment with anti-tuberculosis drugs and steroids, the patient showed clinical improvement. Although tuberculous pericarditis usually presents as pericardial effusion or constrictive pericarditis, it can also present as a pericardial mass mimicking thymic carcinoma on CT. Therefore, we suggest that tuberculous pericardial abscess should be included in the differential diagnosis of a mediastinal mass in Korea, with intermediate tuberculosis prevalence.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.38-47
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• 2012

Background: The prevalence rate of pulmonary tuberculosis (PTB) is steadily decreasing in South Korea. However, PTB is a disease with relatively high mortality and morbidity rates throughout Korea. Although there are many studies and statistics about the risk factors of PTB mortality in many countries, there are only a limited number of domestic papers on this topic. The aim of this study is to determine predictive factors for mortality among in-hospital patients associated with PTB. Methods: From December 2006 to January 2011, we reviewed medical records of 2,122 adult patients diagnosed with tuberculosis at a single tertiary hospital in a suburban area. In this study period, 960 patients were diagnosed with PTB by positive Acid fast bacilli smear and/or mycobacterial culture of the respiratory specimen. We compared the groups of patients deceased and patients discharged alive with PTB. The number of dead patients was 82 (47 males, 35 females). Results: Mortality was significantly associated with increased values of white blood cells (WBC), blood urine nitrogen (BUN), creatinine, C-reactive protein (CRP), numbers of involved lung field, and length of hospitalization. Also, it was associated with the decreased values of hemoglobin, lymphocyte, sodium, albumin, and cholesterol. Furthermore, admission through the emergency department, initial intensive care unit admission, and drug resistant PTB affected mortality in PTB patients. Independent predictors associated with PTB mortality are BUN, initial intensive care unit care, and admission during treatment of tuberculosis. Conclusion: In our study, mortality of pulmonary tuberculosis was related with parameters associated with nutritional status, disease severity at the time of admission, and drug resistance.

• Tuberculosis and Respiratory Diseases
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• v.70 no.4
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• pp.342-346
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• 2011

Herein we report the case of a 71-year-old woman who complained of fatigue and enlarged right axillary lymph nodes for 18 months. At her first visit, her chest X-ray showed diffuse nodular opacities in both lung fields. Initial excisional biopsy of the axillary lymph nodes showed granulomatous lesions and acid fast bacilli were seen on Ziehl-Neelsen staining. However, even after 15 months of anti-tuberculosis (TB) medication, her right axillary lymph nodes were enlarged. We re-performed an excisional biopsy of the nodes, which showed Hodgkin's lymphoma (HL). A retrograde review of the biopsy before anti-tuberculous medication, revealed HL coexisting with TB. HL and TB cause difficulties in differential diagnosis due to similarities in clinical course, imaging procedures and histopathological analysis of the involved tissue. Therefore, it is important to consider the possibility of concurrent HL and TB when patients who undergo treatment for TB or chemotherapy for lymphoma complain of persistent systemic symptoms or enlarged lymph nodes.

• Tuberculosis and Respiratory Diseases
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• v.69 no.6
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• pp.469-473
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• 2010

Nocardia farcinia, an aerobic, gram-positive bacilli actinomycetes of the genus Nocardia, is an uncommon pathogen found in humans. The most common Nocardia infection sites are the lung, central nervous system, and skin. Even though hematogenous dissemination can occur, isolation of the organism from blood cultures is very rare. We report a case of Nocardia infection that was isolated on blood cultures. A 59-year-old male with a medical history that includes a liver transplantation 6-years prior due to hepatocellular carcinoma secondary to chronic hepatitis B, developed pneumonia and was transferred to Severance Hospital. At the time of admission, the patient's initial exam showed hypothermia, tachypnea, and hypotension. His chest radiograph showed severe pneumonia and a large abscess on left upper lobe. Under the presumptive diagnosis of bacterial pneumonia or other opportunistic infection, we started broad spectrum antibiotics. However, he developed Nocardia sepsis, rapidly deteriorated, and subsequently died.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.199-204
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• 2013

Background: The number of patients with pulmonary disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. The aim of this study was to evaluate long-term trends in the NTM recovery rate from respiratory specimens over a 10-year period in a tertiary referral hospital in South Korea. Methods: We retrospectively reviewed the records of mycobacterial cultures of respiratory specimens at Samsung Medical Center from January 2001 to December 2011. Results: During the study period, 32,841 respiratory specimens from 10,563 patients were found to be culture-positive for mycobacteria. These included 12,619 (38%) Mycobacterium tuberculosis and 20,222 (62%) NTM isolates. The proportion of NTM among all positive mycobacterial cultures increased from 43% (548/1,283) in 2001 to 70% (3,341/4,800) in 2011 (p<0.001, test for trend). The recovery rate of NTM isolates from acid-fast bacilli smear-positive specimens increased from 9% (38/417) in 2001 to 64% (1,284/1,997) in 2011 (p<0.001, test for trend). The proportion of positive liquid cultures was higher for NTM than for M. tuberculosis (p<0.001). The most frequently isolated NTM were Mycobacterium avium-intracellulare complex (53%) and Mycobacterium abscessus-massiliense complex (25%). Conclusion: The recovery rate of NTM from respiratory specimens in South Korea has increased steadily.

• The Korean Journal of Nuclear Medicine
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• v.34 no.2
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• pp.129-134
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• 2000

Purpose: It is difficult to determine the activity of tuberculosis radiologically. Therefore there have been efforts to assess the activity using radiopharmaceuticals such as $^{67}Ga,\;^{99m}Tc-tetrofosmin,\;and\;^{99m}Tc-MIBI$. But there may be some discrepancy in defining the term 'activity' between clinicians and nuclear physicians. While negative conversion of sputum acid fast bacilli (AFB) is defined as 'disappearance of activity' by clinicians, a loss of uptake in previously positive lesion is accepted as 'disappearance of activity' by nuclear physicians. We designed a prospective study to see if the negative conversion of sputum AFB could directly match the disappearance of radioactivity of the lesion. Materials and Methods: Fifteen patients with bacteriologically confirmed active localized pulmonary tuberculosis were scanned 10 and 60 min after intravenous injection of 550 MBq $^{99m}Tc$-MIBI. In 6 patients, who showed negative conversion of sputum AFB after 3-7 months of chemotherapy, $^{99m}Tc$-MIBI scan was repeated. For the purpose of comparison, target/nontarget ratios of the lesions were determined. Results: 12/15 (80%) patients with active pulmonary tuberculosis showed increased uptake of $^{99m}Tc$-MIBI in tuberculous lesion. After negative conversion of sputum AFB, 5/6 (83%) patients still showed increased uptake, although the intensity of uptake decreased. Conclusion: Uptake of radioactivity decreased but did not disappear after negative conversion of sputum AFB. $^{99m}Tc$-MIBI scan may be useful to address the degree of inflammation of pulmonary tuberculous lesion, but the uptake did not directly match the activity defined by positivity of sputum AFB. We nuclear physicians might have used the term 'activity' somewhat differently from clinicians who treat patients with tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.61 no.1
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• pp.54-59
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• 2006

Background: Although there have been several studies regarding the clinical value of an automated TB-PCR study using sputum, bronchial washing, and other body fluid samples for the detection of pulmonary tuberculosis, there are only a few reports on the use of fresh tissue samples. Materials and methods: The acid-fast bacilli stain(AFB), tuberculosis culture, automated TB-PCR study, and histopathology examination were performed in 42 fresh tissue samples. Results: Among the 42 cases, 18 cases were diagnosed with tuberculosis based on the clinical findings. Sixteen of the 18 cases were TB-PCR positive and of these 16 cases, only 2 cases were positive in the AFB stain or culture study. However, all 18 cases showed the histopathology findings of chronic granulomatous inflammation that was compatible with tuberculosis. Based on the clinical findings, the sensitivity, specificity, positive predictability, and negative predictability of the automated TB-PCR study were 88.9%, 100%, 100%, and 92.3% respectively. Conclusion: An automated TB-PCR assay is an important diagnostic tool for diagnosing tuberculosis in fresh tissue samples.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1782-1789
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• 2012

We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(${\gamma}$-glutamic acid) (${\gamma}$-PGA). ${\gamma}$-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated ${\gamma}$-PGA was synthesized by covalent coupling between the carboxyl groups of ${\gamma}$-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded ${\gamma}$-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated ${\gamma}$-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated ${\gamma}$-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked ${\gamma}$-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels in aqueous solution were $136.3{\pm}37.6$ nm and $-32.5{\pm}5.3$ mV, respectively. The loading amount of Dox was approximately 38.7 ${\mu}g$ per mg of ${\gamma}$-PGA nanogel. The Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1-10 mM). Through fluorescence microscopy and FACS, the cellular uptake of ${\gamma}$-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of ${\gamma}$-PGA nanogels. The bio-derived ${\gamma}$-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.

• Journal of Korean society of Dental Hygiene
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• v.5 no.2
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• pp.131-145
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• 2005

There are normal inhabitants doing medically useful functions in the body. There are many kinds of bacteria performing specific functions in the oral cavity. Two strains of lactic add bacteria were isolated from normal inhabitants of children's oral cavity, which inhibited the production of volatile sulfur compounds by anaerobic bacteria. The authors identified the isolates by 16S rDNA partial sequencing. 1. Two isolates were Gram-positive bacilli and produced hydrogen peroxide. 2. When Streptococcus mutans was cultured in the media, the mean weight of formed artificial plaque on the orthodontic wires was $124.4{\pm}30.4$ mg, whereas being reduced to $5.2{\pm}2.0$ mg and $10.6{\pm}6.6$ mg in the media cultured with Streptococcus mutans and each isolate, respectively(p<0.05). 3. The number of viable cells of Streptococcus mutans was $3.4{\times}10^9$ per ml in the cultured solution, whereas those of Streptococcus mutans in the combined culture with each of isolates were $4.6{\times}10^8$ and $2.4{\times}10^8$ per ml. 4. The optical density was 1.286 in the supernatant of Fusoacterium nucleatum after vortexing for 30 minutes, whereas in the supernatant of combined Fusoacterium nucleatum and each isolate, they were reduced to 0.628 and 00497, which the percentages of coaggregation between them were 2904% and 57.8%, respectively. 5. The optical density of Fusoacterium nucleatum precipitate was 1.794 in the culture media containing cysteine and $FeSO_4$ being reduced to 1.144 and 0.915 in the coaggregated precipitates of Fusoacterium nucleatum and each isolate. 6. The similarity values of 16S rDNA sequence between each of isolates and Lactobacillus salivarius subsp. salicinius were 99.60% and 99.73%, respectively, meaning that isolates were Lactobacillus salivarius subsp. salicinius. These results indicated that two strains isolated from children's saliva, which inhibited the formation of plaque and the production of volatile sulfur compounds, were identified as Lactobacillus salivarius subsp. salicinius.