• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.378-383
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• 1993

Background: In recent reports, it has been reported that increased coagulation and decreased fibrinolytic activity has been responsible for abnormal fibrin turnover in exudative pleural effusion. In the cases of empyema, the fibrinopurulent stage is characterized by the fibrin deposition resulting in formation of limiting membranes in the visceral and parietal pleura. Recently attention has been focused on intrapleural fibrinolytic therapy capable of removing intrapleural fibrin deposits by urokinase (UK) in the treatment of empyema. However, these clinical trials have provided the clinical evidences for resolution of pleural loculation after intrapleural urokinase injection (UK-injection), the profiles of fibrinolytic activity following the treatment were still not investigated. Therefore in order to demonstrate the fibrinolytic evidences behind the clinical efficacy of intracavitary UK-injection, we examined intrapleural plasminogen activator activity (PA-activity) and D-dimer (D-Di) concentrations before and after each repeated UK-injection into the pleura in subjects with loculated empyema cavity. Methods: In a group of 14 patients with multiple loculated empyema cavity, PA-activity and D-Di concentrations were measured before and after repeated UK-injection. One hundred thousand IU of UK was injected at each time and all sujects had at least two times of UK injection accoring to clinical decisions. Nine out of 14 sujects had three times of UK-injection. Results: The mean (${\pm}SE$) PA-activity prior to treatemnt was $10.5{\pm}7.0$ and it was increased to $91.9{\pm}27.0,\;432.3{\pm}177.1,\;170.0{\pm}85.3$ IU tPA/ml after first, second and third time of UK-injection respectively (p<0.01). D-Di concentrations were also increased from $4.16{\pm}1.06{\times}10^5$ to $9.62{\pm}1.54{\times}10^5,\;12.31{\pm}1.89{\times}10^5,\;8.54{\pm}1.56{\times}10^5$ ng/ml in the same order as above (p<0.05). Conclusion: The suppressed fibrinolytic activity in the empyema cavity get removed sinificantly after inrracavitary injection of urokinase by generation of additional intrapleural plasmin.

• Journal of the Korean Chemical Society
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• v.62 no.4
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• pp.299-313
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• 2018

Inquiry-centered education is important in science education, but in the actual education field, scientific research is being done in a uniform manner due to realistic difficulties. In this study, we use RS (Reverse Science) as a secondary chemistry class to provide opportunities for students to engage in inquiry learning and scientific thinking through process-oriented activities. In this study, we developed and applied it to explore the effects on the scientific inquiry abilities of middle school students and checked the students' perception of it. For the application of the program, 128 students were selected from 6 classes of the 2nd grade in D district middle school, 64 from the experimental group and 64 from the comparative group. The experimental group taught RSP-based the chemistry inquiry programs and the comparative group taught instructor-led classes and verification experiments on the same topic over the seventh hour with three themes. In addition, we analyzed the results of the pre- and post-test by using the science inquiry ability test, and discussed the effects of the program based on the students' perceptions through class observation, student activity area, questionnaire and interview. As a result, the class using the program showed statistically significant changes in the science inquiry ability of secondary school students. Specifically, the experimental group was found to be significant in its prediction among the subcomponents of basic exploration ability compared to the comparative group. The differences have also been shown to be significant in terms of data translation, hypothesis setup and variable control, which are subcomponents of integrated exploration capabilities (p <. 05). In addition, students became interested in the process of creating the theory of science, and were highly interested in collaborating with their friends. It also provided students with opportunities to experience scientific thinking through process-oriented inquiry. Finally, based on the positive impact of the RSP-based chemistry inquiry program on students, we were able to identify the potential use of the program.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.14 no.3
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• pp.59-71
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• 2019

The domestic unemployment rate is now seriously increasing due to the impact of the international trend of incurring high costs using only a small number of manpower in a situation where the business has been being reduced in size. The nation is taking start-up promotion policies as a way to overcome the problem, but with the advent of excessive entrepreneurs and their concentration on specific areas, their survival is in an unclear situation. Thus, this study was intended to provide a useful direction for successful start-ups by identifying the impact of entrepreneurial motivation and entrepreneurship, internal characteristics of entrepreneurs, and of competency characteristics, external characteristics of them, on sustainability through business performance. Thus, the purpose of this study was to provide a useful direction for successful start-ups by identifying the impact of entrepreneurial motivation and entrepreneurship, internal characteristics of entrepreneurs, competency, and external characteristics, on sustainability through business performance. The result of verifying the hypothesis has showed that entrepreneurial motivation, entrepreneurship, and competency characteristics had a positive effect on business performance, and on the other hand, the business performance had a positive effect on sustainability. In addition, in terms of the impact of entrepreneurial motivation, entrepreneurship, and competency characteristics on sustainability, all of them had mediating effects on business performance. It is obvious that studies on the factors affecting business performance and corporate sustainability up to now have been carried out by only collecting the independent variables of this study individually or two of them. so it is judged that if the study, which has verified the practical direction in general through the verification of entrepreneurs's internal and external characteristics from various angles, is performed more comprehensively along with the addition of background characteristics of entrepreneurs, such as characteristics of start-up preparation, etc., in the future, more in-depth results will be able to be obtained.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.