The retinoic acid (RA) plays an important role in the growth and development of many cells, and bioactive RA concentration is regulated by several enzymes, including CYP26A1. The expression of the CYP26A1 gene is regulated by RA, and the CYP26A1 gene is one of the candidates for RA-responsive genes. Although CYP26A1 genes are cloned from several animals, cloning of the CYP26A1 gene from cows has not been reported yet. The promoter region of CYP26A1 from cows was cloned by PCR and analyzed by sequence alignment with human and mouse CYP26A1. The RA-responsive element (RARE), DR-5 (ttggg), was located in this region and was perfectly conserved. The promoter region of bovine CYP26A1, which contains DR-5, was ligated to the luciferase reporter gene on transient transfection assays. The expression of CYP26A1-Luc promoter was activated by ATRA treatment in lung-derived mtCC cells. Co-transfection with RAR-α or -β with ATRA significantly activates the expression of CYP26A1-Luc promoter; however, it was less effective with either RAR-γ or RXR-γ. In addition, the endogenous gene expressions measured by Q-RT-PCR in mtCC cells were not significantly affected by ATRA treatment for 2 days; however, the expression of the endogenous CYP26A1 gene was diminished sharply at day 3 with ATRA treatment. In conclusion, the promoter region of bovine CYP26A1 contains conserved DR-5 RARE, which functions as a binding site for RAR-α or -β, and it is involved in the regulation of CYP26A1 gene expression and the control of RA signaling in mtCC cells.
Background : Recently, there are many patients with lipoid pneumonia by ingestion of shark liver oil in Korea, but only a few animal experimentations have been carried out. The purpose of this study is to evaluate sequential change of the lung after aspiration of shark liver oil and to provide the radiologic-pathologic correlation. Methods: A single intratracheal administration of shark liver oil was given to 14 white rabbits. They were then sacrificed sequentially from 1 week to 6 weeks after injection. We investigated the HRCT and pathologic findings Results: One was sudden death immediately after injection. Six of the 13 rabbits showed pneumonic infiltrations on the HRCT. There were air space consolidation with air-bronchogram on the HRCT of the first week. They were associated with the volume loss in the 4th week, and the traction bronchiectasis in the 6th week. The important pathologic findings were peribronchial alveolar inflammation with septal widening and cuboidal metaplasia of the alveolar wall. The number of macrophages in an alveoli was peaked in the second week and then gradually decreased. On the 6th week, we could find the proliferation of fibroblasts. Conclusion: We can prove the development of lipoid pneumonia after aspiration of squalene by animal experimentation, and the understanding of HRCT and pathologic findings may be helpful in proper evaluation of pneumonia due to aspiration of fish-extracted lipid.
To investigate the etiology, pathogenicity and virological properties of NYJ-1-87 strain of Aujeszky's disease virus (ADV) that was isolated from the diseased piglet in Korea, the virus at $10^{6.0}TCID_{50}/0.1ml$ was inoculated intranasally and subcutaneously into 30 to 35 days-old piglets. Results obtained through the experiments were summarized as follows. 1. Ten of the infected piglets were clinically observed for 15 days. On the 2nd day post-inoculation(pi), the signs of pyrexia, anorexia and convulsion were noted. On the 4th to 7th days pi, nervous signs of incoordination and intermittent spasm were shown in the most of piglets, and one out of 5 piglets infected intranasally was died with severe nervous signs at the 7th day pi. The signs became relieved on the 8th day pi and all of remainder were completely recovered on the 13th to 14th days pi. 2. In hematological study, prominent decrease in the number of total leukocyte and lymphocyte was shown in the ADV-infected piglets on the 6th day pi. On the 8th day pi, the cell numbers were slightly increased and returned to normal level on the 10th day pi. 3. Viral excretion of the ADV-inoculated piglets was examined by swabbing of nasal and oral cavities, and rectal feces. During the periods of the 3rd to 11th days pi, the virus was excreted intermittently from nasal and oral cavities, and rectal feces. The nasal excretions were shown the highest virus concentration of $10^{5.2}TCID_{50}/0.1ml$ at the 5th day pi. 4. Recovery of the inoculated virus from various organs of the piglets that were died or experimentally slaughtered was attempted, and the virus was isolated from the tissues of brain and tonsil by the cultured cell-inoculation method. The highest recovery rate was noted in the tonsil. By indirect immunofluorescence antibody assay using ADV-monoclonal antibody, the viral antigens were detected in tissues of spleen and liver as well as brain and tonsil on the 7th to 9th days pi. The virus was not isolated from blood and the tissues of lung and kidney throughout the experiments. 5. Titers of virus neutralizing antibody in the piglets experimentally infected with ADV became increased after the 6th to 9th days pi in both of intranasal and subcutaneous inoculation showing the highest titers of 64 to 128 on the 29th day pi. When the antibody levels were measured by radial immunodiffusion enzyme assay, the reactive diameter was enlarged to be positive after the 4th to 6th days pi in both of intranasal and subcutaneous inoculation showing the largest diameter of 13 to 14mm on the 29th day pi.
Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$$70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.
Kim, Seo Woo;Kim, Sae In;Lee, Seok Jeong;Lee, Jin Hwa;Ryu, Yun Ju;Shim, Sung Shine;Kim, Yookyoung;Lee, Mi Ae;Chang, Jung Hyun
Tuberculosis and Respiratory Diseases
/
v.78
no.1
/
pp.1-7
/
2015
Background: The incidence of tuberculosis (TB) in Korea is relatively high compared to the other Organisation for Economic Co-operation and Development (OECD) countries, with a prevalence of 71 per 100,000 in 2012, although the incidence is declining. Real-time polymerase chain reaction (PCR) has been introduced for the rapid diagnosis of TB. Recently, its advantage lies in higher sensitivity and specificity for the diagnosis of TB. This study evaluated the clinical accuracy of real-time PCR using respiratory specimens in a clinical setting. Methods: Real-time PCR assays using sputum specimens and/or bronchoscopic aspirates from 2,877 subjects were reviewed retrospectively; 2,859 subjects were enrolled. The diagnosis of TB was determined by positive microbiology, pathological findings of TB in the lung and pleura, or clinical suspicion of active TB following anti-TB medication for more than 6 months with a favorable response. Results: Sensitivity, specificity, and accuracy were 44%, 99%, and 86% from sputum, and 65%, 97%, and 87% from bronchoscopic aspirates, respectively. For overall respiratory specimens, sensitivity was 59%, specificity was 98%, and accuracy increased to 89%. Conclusion: Positivity in real-time PCR using any respiratory specimens suggests the possibility of active TB in clinically suspected cases, guiding to start anti-TB medication. Real-time PCR from selective bronchoscopic aspirates enhances the diagnostic yield much more when added to sputum examination.
Sa, Young-Jo;Kim, Yong-Han;Nam, Sang-Yong;Sim, Sung-Bo;Lee, Sun-Hee;Park, Jae-Kil
Journal of Chest Surgery
/
v.40
no.9
/
pp.617-623
/
2007
Background: Invasive pulmonary aspergillosis, a frequent fungal infection in immunocompromised patients, is known to have a poor prognosis despite the use of antifungal therapy in leukemic patients. We studied the outcome of surgical resection of invasive pulmonary aspergillosis where bleeding tendency, localized recurrence of infection, and incidence could be reduced. Material and Method: We retrospectively reviewed 14 patients with a hematological malignancy where invasive pulmonary aspergillosis was diagnosed during the 10 years between 1998 and 2007. From the medical records, we reviewed the type and treatment of the hematological malignancy, including the diagnostic methods of invasive pulmonary aspergillosis, the preoperative hematological conditions and their management, and the surgical methods and records. We also analyzed the development of postoperative complications and patient mortality, the recurrence of postoperative invasive pulmonary aspergillosis, and if the patients had a bone marrow transplant. Result: Fourteen patients with invasive pulmonary aspergillosis and a hematological malignancy underwent a pulmonary lobectomy. One patient had a complication of bronchopleural fistula, but there were no other serious complications such as bleeding or wound infection, and none of the patients died postoperatively. Conclusion: We have shown that pulmonary lobectomy is a safe and effective therapy for invasive pulmonary aspergillosis in patients with hematological malignancies that allow further treatment of the hematological malignancy.
Cho Eun Seob;lung Choon Coo;Kim Chul Won;Sohn Sang Cyu
Journal of Life Science
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v.15
no.6
s.73
/
pp.879-883
/
2005
This study was differentiated between Korea and China arkshells using PCR-aided RFLP method which could identify the variation for inter-and intra-species of arkshell (Scapharca broughtonii Schrenck) at the level of DNA. The DNA fragment patterns were compared after digesting gene of mitochondrial 16S rDNA with 8 kinds of restriction enzymes. A 720 bp DNA fragment corresponding to 16S rDNA gene was amplified by PCR with primers ArkF-3 and ArkR-3. PCR products were cut by restriction enzymes (Pvull, BamHI, Hinfl, HaeIII, EcoRI, RsaI, Ksp221, and BstX21), and RFLP pattern was studied. A unique 275 bp DNA band was observed in the samples from Dukyang, Gamak, Namhae, Jinhae, and Taean in Korea when treated by Hinfl, but Chinese arkshell did not show. Treatment of HaeIII could discriminate the sample of Namhae and Jinhae from Dukyang/Gamak/Taean, as well as Korean and Chinese arkshell based on a 700 bp. However, PuvII, BamHI, EcoRI, RsaI, Ksp221, and BstX21 showed the same of 700 bp band in Korean and Chinese arkshell. The phylogenetic tree inferred from PCR-RFLP pattern comparsion in Korean arkshell was different that the distance between Dukyang/Gamak/Taean and Namhae/Jinhae was approximately 7. In particular, the distance between Korean and Chinese arkshell was 25. Consequently, HinfI and HaeIII played an important role in a reliable molecular tool for rapid discriminating Korean and Chinese arkshell, as well as a intra-species in Korea.
Park, Young-Mi;Yoon, Ho-Il;Sohn, Cheong-Min;Choue, Ryo-Won
Journal of Nutrition and Health
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v.41
no.4
/
pp.307-316
/
2008
The purpose of the study was to investigate nutritional status of chronic obstructive pulmonary disease (COPD) patients and to find out the differences according to the stages of disease. From March to October, 2006, 41 stable male patients of mild to severe COPD patients were recruited from Seoul National University hospital. The patients' of body weight and fat free mass were assessed by bioelectrical impedance analysis. The nutritional status of the patients was also assessed by 3-day recall, index of nutritional quality (INQ), dietary diversity score (DDS), dietary variety score (DVS), food group index pattern and dietary quality index (DQI). The total of 41 patients were classified into three groups, stage I, stage II and stage III groups according to the classification of Global Initiative for Chronic Obstructive Lung Disease (GOLD) standard. The mean age of the patients in each stage were 67.2-66.9 years showing no significant difference. The ratio of $FEV_1$/FVC were $57.5{\pm}7.3$, $46.9{\pm}7.6$ and $38.2{\pm}6.8%$, respectively showing significant differences according to the stages of disease. The fat free mass of the stage II ($48.2{\pm}4.7kg$) and III ($47.3{\pm}4.5kg$) was significantly lower than that of stage I ($53.1{\pm}6.9kg$) patients. There were significant correlation of fat free mass with $FEV_{1}$, and BMI (body mass index) with $FEV_{1}$/FVC ratio (p < 0.05). COPD patients showed the diet-related clinical symptoms of anorexia, dyspnea, dyspepsia, and chewing difficulty. Daily intakes of calorie, K, vitamin $B_2$ and folate of the patients were very low ($83.8{\pm}20.7%$, $58.9{\pm}14.4%$, $70.7{\pm}19.6%$ and $74.4{\pm}10.2%$, respectively) however, they did not significantly different according to the stages of disease. Daily intake of calcium was significantly lower in the stage III patients (p < 0.05). The mean scores of dietary variety score was significantly lower in the stage III patients (p < 0.001). Dietary quality index of the patients were not different among the stages of disease and the scores indicated poor quality of diet. As a summary, we found that body fat free mass, regularity of exercise, frequency of having snacks and dietary variety score were significantly associated with the severity of chronic obstructive pulmonary disease.
Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.
Choi, Bo Hye;Kim, Young Jae;Choi, Seung Jun;Kim, Kwang Gi
Journal of Biomedical Engineering Research
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v.39
no.6
/
pp.229-236
/
2018
Liver cancer is one of the highest incidents in the world, and the mortality rate is the second most common disease after lung cancer. The purpose of this study is to evaluate the diagnostic ability of deep learning in the classification of malignant and benign tumors in CT images of patients with liver tumors. We also tried to identify the best data processing methods and deep learning models for classifying malignant and benign tumors in the liver. In this study, CT data were collected from 92 patients (benign liver tumors: 44, malignant liver tumors: 48) at the Gil Medical Center. The CT data of each patient were used for cross-sectional images of 3,024 liver tumors. In AlexNet and VggNet, the average of the overall accuracy at each image size was calculated: the average of the overall accuracy of the $200{\times}200$ image size is 69.58% (AlexNet), 69.4% (VggNet), $150{\times}150$ image size is 71.54%, 67%, $100{\times}100$ image size is 68.79%, 66.2%. In conclusion, the overall accuracy of each does not exceed 80%, so it does not have a high level of accuracy. In addition, the average accuracy in benign was 90.3% and the accuracy in malignant was 46.2%, which is a significant difference between benign and malignant. Also, the time it takes for AlexNet to learn is about 1.6 times faster than VggNet but statistically no different (p > 0.05). Since both models are less than 90% of the overall accuracy, more research and development are needed, such as learning the liver tumor data using a new model, or the process of pre-processing the data images in other methods. In the future, it will be useful to use specialists for image reading using deep learning.
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