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The Effect of Interferon-γ on Bleomycin Induced Pulmonary Fibrosis in the Rat (Interferon-γ 투여가 쥐에서의 Bleomycin 유도 폐 섬유화에 미치는 영향)

  • Yoon, Hyoung Kyu;Kim, Yong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.51-66
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    • 2004
  • Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

The Impact of Human Resource Innovativeness, Learning Orientation, and Their Interaction on Innovation Effect and Business Performance : Comparison of Small and Medium-Sized vs. Large-Sized Companies (인적자원의 혁신성, 학습지향성, 이들의 상호작용이 혁신효과 및 사업성과에 미치는 영향 : 중소기업과 대기업의 비교연구)

  • Yoh, Eunah
    • Korean small business review
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    • v.31 no.2
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    • pp.19-37
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    • 2009
  • The purpose of this research is to explore differences between small and medium-sized companies and large-sized companies in the impact of human resource innovativeness(HRI), learning orientation(LO), and HRI-LO interaction on innovation effect and business performance. Although learning orientation has long been considered as a key factor influencing good performance of a business, little research was devoted to exploring the effect of HRI-LO interaction on innovation effect and business performance. In this study, it is investigated whether there is a synergy effect between innovative human workforce and learning orientation corporate culture, in addition to each by itself, to generate good business performance as well as a success of new innovations in the market. Research hypotheses were as follows, including H1) human resource innovativeness(HRI), learning orientation(LO), and interactions of HRI and LO(HRI-LO interaction) positively affect innovation effect, H2) there is a difference of the effect of HRI, LO, and HRI-LO interaction on innovation effect between large-sized and small-sized companies, H3) HRI, LO, HRI-LO interaction, innovation effect positively affect business performance, and H4) there is a difference of the effect of HRI, LO, HRI-LO interaction, and innovation effect on business performance between large-sized and small-sized companies. Data were obtained from 479 practitioners through a web survey since the web survey is an efficient method to collect a national data at a variety of fields. A single respondent from a company was allowed to participate in the study after checking whether they have more than 5-year work experiences in the company. To check whether a common source bias is existed in the sample, additional data from a convenient sample of 97 companies were gathered through the traditional survey method, and were used to confirm correlations between research variables of the original sample and the additional sample. Data were divided into two groups according to company size, such as 352 small and medium-sized companies with less than 300 employees and 127 large-sized companies with 300 or more employees. Data were analyzed through t-test and regression analyses. HRI which is the innovativeness of human resources in the company was measured with 9 items assessing the innovativenss of practitioners in staff, manager, and executive-level positions. LO is the company's effort to encourage employees' development, sharing, and utilizing of knowledge through consistent learning. LO was measured by 18 items assessing commitment to learning, vision sharing, and open-mindedness. Innovation effect which assesses a success of new products/services in the market, was measured with 3 items. Business performance was measured by respondents' evaluations on profitability, sales increase, market share, and general business performance, compared to other companies in the same field. All items were measured by using 6-point Likert scales. Means of multiple items measuring a construct were used as variables based on acceptable reliability and validity. To reduce multi-collinearity problems generated on the regression analysis of interaction terms, centered data were used for HRI, LO, and Innovation effect on regression analyses. In group comparison, large-sized companies were superior on annual sales, annual net profit, the number of new products/services in the last 3 years, the number of new processes advanced in the last 3 years, and the number of R&D personnel, compared to small and medium-sized companies. Also, large-sized companies indicated a higher level of HRI, LO, HRI-LO interaction, innovation effect and business performance than did small and medium-sized companies. The results indicate that large-sized companies tend to have more innovative human resources and invest more on learning orientation than did small-sized companies, therefore, large-sized companies tend to have more success of a new product/service in the market, generating better business performance. In order to test research hypotheses, a series of multiple-regression analysis was conducted. In the regression analysis examining the impact on innovation effect, important results were generated as : 1) HRI, LO, and HRI-LO affected innovation effect, and 2) company size indicated a moderating effect. Based on the result, the impact of HRI on innovation effect would be greater in small and medium-sized companies than in large-sized companies whereas the impact of LO on innovation effect would be greater in large-sized companies than in small and medium-sized companies. In other words, innovative workforce would be more important in making new products/services that would be successful in the market for small and medium-sized companies than for large-sized companies. Otherwise, learning orientation culture would be more effective in making successful products/services for large-sized companies than for small and medium-sized companies. Based on these results, research hypotheses 1 and 2 were supported. In the analysis of a regression examining the impact on business performance, important results were generated as : 1) innovation effect, LO, and HRI-LO affected business performance, 2) HRI by itself did not have a direct effect on business performance regardless of company size, and 3) company size indicated a moderating effect. Specifically, an effect of the HRI-LO interaction on business performance was stronger in large-sized companies than in small and medium-sized companies. It means that the synergy effect of innovative human resources and learning orientation culture tends to be stronger as company is larger. Referring to these result, research hypothesis 3 was partially supported whereas hypothesis 4 was supported. Based on research results, implications for companies were generated. Regardless of company size, companies need to develop the learning orientation corporate culture as well as human resources' innovativeness together in order to achieve successful development of innovative products and services as well as to improve sales and profits. However, the effectiveness of the HRI-LO interaction would be varied by company size. Specifically, the synergy effect of HRI-LO was stronger to make a success of new products/services in small and medium-sized companies than in large-sized companies. However, the synergy effect of HRI-LO was more effective to increase business performance of large-sized companies than that of small and medium-sized companies. In the case of small and medium-sized companies, business performance was achieved more through the success of new products/services than much directly affected by HRI-LO. The most meaningful result of this study is that the effect of HRI-LO interaction on innovation effect and business performance was confirmed. It was often ignored in the previous research. Also, it was found that the innovativeness of human workforce would not directly influence in generating good business performance, however, innovative human resources would indirectly affect making good business performance by contributing to achieving the development of new products/services that would be successful in the market. These findings would provide valuable managerial implications specifically in regard to the development of corporate culture and education program of small and medium-sized as well as large-sized companies in a variety of fields.

A Study on the Visions of Zechariah in the Old Testament from a Perspective of Analytical Psychology (구약성서 '스가랴'서의 환상에 대한 분석심리학적 연구)

  • Sang Ick Han
    • Sim-seong Yeon-gu
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    • v.29 no.1
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    • pp.1-45
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    • 2014
  • Mystic experience such as seeing an vision could be explained as experiencing elusive and mysterious unique existence in religious way. In depth psychology, which is based on unconsciousness like analytical psychology, this could be explained as a something that gives a meaning of life and purpose through discovering health and healing. The importance of primodial experience in depth psychology is that it can possibly discover the base of present acts. In Christian theology, symbolic mystery and truth of religious experience that appear in Christian tradition have interest on human situation. These two fields' approach methods are different, but both show common interest on unique experience which can be said properly as raw experience. Various visions appear in many parts of the Bible. Among many visions, the book of Zechariah, one of the 12 Prophets, describes rich and diverse 8 visions through chapter 1 to chapter 8. However, due to the Genre of revelation, it lacks historicity, and because of vagueness and symbolic meanings, its visions are hard to understand and interpret. Theologically, visions of Zechariah show communality of Israelites by reconstructing kingdom of Judah and church in a way of historical circumstances. Though, these visions could deliver the meaning of an ethnical aspect as reporting continuous conversation between the God and humans. Furthermore, it could mean a personal aspect of the Prophet Zechariah as reaching for a opportunity of new change. Moreover, those who read these visions could try to interpret the meanings of various images which represent meeting mysterious existences. Therefore, the Author would concentrate on the fact that 8 visions in the book of Zechariah, which has not been received much attention to neither Christians nor non-believers, develop in chiastic structure (stylistic contrast), so that tries to interpret the first, second, seventh, and the eighth visions in analytic psychology way. In visions of Zechariah, excepting the 4th vision which probably was inserted later, rest of 7 visions each shows the stage of the hours of darkness. 1st to 3rd visions represent evening, 5th vision represents deep in the night, and 6th to 8th visions represent dawn to morning. Moreover, since structure of visions arranged in chiastic way, horse appears in 1st and 8th vision, measuring rope and measure tools are used as main motif in 2nd and 7th vision. However, same motifs could have different symbolic meanings and roles as visions are formed in different situations and conditions. In the first vision, angels who ride horses look around the world and report it is calm and peaceful. Concerning the political situation back in the day, the world being calm and peaceful in the beginning of evening means that it is not ready to change to a whole new world. Psychologically, if there is no readiness to adopt new world, it means being hopeless. It is sending you a message to get out of those kinds of situation. Moreover, appearance of four angels who rode red, brown, and white horses to a myrtus tree in the valley means that it is time for individuation and it is right and good timing for changing. In second vision, you will be able to see that Israelites had long years being caught in the shadows by foreign country, and long years succumbed by the strength of four horns, which shows the progress of renewing strength and being oneness with oneself from overwhelmed situation by paternity. In seventh vision, meaning of two women bringing the godness of the sky, who were locked up in a rice basket, back to the temple in Babylon is going towards in a level of Self-actualization by separating one's ego captured excessively by matherhood and putting back to a place where it was before. In eighth vision, chariots pulled by horses are scattered far and wide, and horses which went to north had rest in the land of North. After horses and chariots are seen between two mountains of bronze with the image of Self and anima/animus. These images can be explained as the changing progress are almost completed and the God and human, in other words Self and ego are being united and is now time for rest. All of 8 visions contains the conversation between angel and Zechariah who willing to know the meaning of visions. Zechariah asks the angel actively about the meaning of visions because of his wish for Israelites to return home and rebuild church. Conversation among the God, Zechariah, who asks questions until he knows everything, an Angel, who gives answer to given questions, is conversation between ego and anima/animus. Eventually, it is a conversation between Self and ego.