• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.3
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• pp.197-205
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• 2007

Angiogenesis is a essential part for bone formation and bone fracture healing. Vascular endothelial growth factor (VEGF), one of the most important molecules among many angiogenic factors, is a specific mitogen for vascular endothelial cells. VEGF-mediated angiogenesis is required for bone formation and repair. However, the effect of VEGF on osteoblastic cells during osteogenesis is still controversial. In recent days, substantial progress have been made toward developing tissue-engineered alternatives to autologous bone grafting for maxillofacial bony defects. Periosteum has received considerable interest as a better source of adult stem cells. Periosteum has the advantage of easy harvest and contains various cell types and progenitor cells that are able to differentiate into a several mesenchymal lineages, including bone. Several studies have reported the bone formation potential of periosteal cells, however, the correlation between VEGF signaling and cultured human periosteal cell-derived osteogenesis has not been fully investigated yet. The purpose of this study was to examine the correlation between VEGF signaling and cultured human periosteal-derived cells osteogenesis. Periosteal tissues of $5\;{\times}\;20\;mm$ were obtained from mandible during surgical extraction of lower impacted third molar from 3 patients. Periosteal-derived cells were introduced into the cell culture and were subcultured once they reached confluence. After passage 3, the periosteal-derived cells were further cultured for 42 days in an osteogenic inductive culture medium containing dexamethasone, ascorbic acid, and ${\beta}-glycerophosphate$. We evaluated the alkaline phosphatase (ALP) activity, the expression of Runx2 and VEGF, alizarin red S staining, and the quantification of osteocalcin and VEGF secretion in the periosteal-derived cells. The ALP activity increased rapidly up to day 14, followed by decrease in activity to day 35. Runx2 was expressed strongly at day 7, followed by decreased expression at day 14, and its expression was not observed thereafter. Both VEGF 165 and VEGF 121 were expressed strongly at day 35 and 42 of culture, particularly during the later stages of differentiation. Alizarin red S-positive nodules were first observed on day 14 and then increased in number during the entire culture period. Osteocalcin and VEGF were first detected in the culture medium on day 14, and their levels increased thereafter in a time-dependent manner. These results suggest that VEGF secretion from cultured human periosteal-derived cells increases along with mineralization process of the extracellular matrix. The level of VEGF secretion from periosteal-derived cells might depend on the extent of osteoblastic differentiation.

• Journal of Periodontal and Implant Science
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• v.29 no.4
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• pp.873-893
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• 1999

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue and repair of function. For more than a decade there have been many efforts to develop materials and bioactive molecule(such as growth factor and differentiation factors) to promote periodontal wound healing. Among the bioactive molecules, bone morphogenetic protein(BMP) was studied for periodontal wound healing. Since Urist demonstrated that demineralized bone matrix could induce the formation of cartilage and bone in ectopic site, many studies on BMP have been reported. Among those BMPs, it was reported that rhBMP-2 enhanced the healing of bone defects in animal studies and clinical studies. However, its efficacy in periodontal regeneration, especially 1-wall intrabony defects is still unknown. The purpose of this study was to examine the effect of rhBMP-2/ACS on the epithelial migration, gingival connective tissue adhesion, cementum formation, alveolar bone regeneration in intrabony defects of dogs. Four millimeter deep and four millimeter wide 1-wall defects were surgically created in the mesial aspects of the 3rd incisors. The test group received rhBMP-2/ACS with a flap procedure and the control underwent buffer/ACS with a flap procedure. Histologic analysis after 8 weeks of healing revealed the following results: 1. The length of epithelial growth(the distance from alveolar crest to the apical end of JE) was $0.9{\pm}1.5mm$ in the control group and $1.2{\pm}1.4mm$ in the test group. There was no statistically significant difference between the two groups. 2. The length of connective tissue adhesion was $2.4{\pm}1.3mm$ in the control group and $1.2{\pm}1.1mm$ in the test group. The control group showed significantly enhanced adhesion(P<0.05). 3. The length of new cementum was $0.9{\pm}1.0mm$ in the control group and $1.7{\pm}0.8mm$ in the test group. The test group showed significantly enhanced cementum regeneration(P<0.05). 4. The length of new bone height was $1.9{\pm}0.6mm$ in the control group and $2.4{\pm}0.9mm$ in the test group. There was no statistically significant difference between the two groups. 5. The new bone area was $4.7{\pm}1.7mm^2$ in the control group and $8.0{\pm}2.0mm^2$ in the test group. The test group showed significantly enhanced bone formed area(P<0.05). 6. The new bone density was $73.0{\pm}8.6%$ in the control group and $66.6{\pm}15.3%$ in the test group. There was no statistically significant difference between the two groups. These results suggest that the use of rhBMP-2 in 1-wall intrabony defects has significant effect on new cementum and new bone formation area, but doesn't have any significant effect on the prevention of junctional epithelium migration and new bone formation height.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Journal of Korean Society of Forest Science
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• v.46 no.1
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• pp.10-20
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• 1980

This experiment was carried out to investigate the effects of physico-chemical properties of soil on the growth of Chamaecyparis obtusa and to apply the results to such rational forest management as yield forecast and selection of suitable species for a given forest stand. The soil properties observed in this experiment were soil pH, exchangeable pH organic matter, total nitrogen, available $P_2O_5$, cation exchange capacity, exchangeable $H^+$, total base and base saturation. Diameter at breast height (DBH), height and volume growth of C. obtusa were observed at 78 sampling sites. Data were processed into the following series for the analysis of multivariates : inner correlation matrix, multiple correlation coefficients, regression coefficients and partial correlation coefficients. The results are summerized as follows : 1. Multiple correlation coefficients between soil properties and DBH of C. obtusa were .364 for 20-year trees, resulting less efficient for estimating the growth of C. obtusa. However, total base, soil pH and base saturation were considerable characters for better estimation. 2. More efficient multiple correlation coefficients were observed between soil properties and height growth than those between soil properties and DBH, showing .443 for 20-year trees and factors affecting the height growth were similar to those of DBH. 3. Extremely low values of multiple correlation coefficients were estimated between physico-chemical properties of soil and volume growth of C. obtusa resulting low efficient estimation. However, total base contributed highly to volume growth of C. obtusa. Accordingly the most contributable factor for estimating the growth of C. obtusa were total base, soil pH and base saturation. Consequently, these results can be effective for selecting of the reforesting site, and less effective for estimating the growth of C. obtusa.

• Analytical Science and Technology
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• v.31 no.4
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• pp.161-170
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• 2018

The epidemic of disorders associated with synthetic stimulants, such as methamphetamine (MA) and amphetamine (AP), is a health, social, legal, and financial problem. Owing to the high potential of their abuse and addiction, reliable analytical methods are required to detect and identify MA, AP, and their metabolites in biological samples. Thus, a dilute-and-shoot liquid chromatography-tandem mass spectrophotometry (LC-MS/MS) was developed for simultaneous determination of MA, 4-hydroxymethamphetamine (4HMA), AP, and 4-hydroxyamphetamine (4HA) in urine. Urine sample ($100{\mu}L$) was mixed with $50{\mu}L$ of mobile phase consisting of 0.4 % formic acid and methanol and $50{\mu}L$ of working internal-standard solution. Aliquots of $8{\mu}L$ diluted urine was injected into the LC-MS/MS system. For all analytes, chromatographic separation was performed using a C18 reversed-phase column with gradient elution and a total run time of 5 min. The identification and quantification were performed by multiple reaction monitoring (MRM). Linear least-squares regression was conducted to generate a calibration curve, with $1/x^2$ as the weighting factor. The linear ranges were 2.0-200, 1.0-800, and 10-2500 ng/mL for 4HA and 4HMA, AP, and MA, respectively. The inter- and intraday precisions were within 6.6 %, whereas the inter- and intraday accuracies ranged from -14.9 to 11.3 %. The low limits of quantification were 2.0 ng/mL (4HA and 4HMA), 1.0 ng/mL (AP), and 10 ng/mL (MA). The proposed method exhibited satisfactory selectivity, dilution integrity, matrix effect, and stability, which are required for validation. Moreover, the purification efficiency of high-speed centrifugation was clearly higher than 6-15 % for QC samples (n=5), which was higher than that of the membrane-filtration method. The applicability of the proposed method was tested by forensic analysis of urine samples from drug abusers.

• Archives of design research
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• v.18 no.4 s.62
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• pp.95-104
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• 2005

The purpose of this study is to estimate the determinants of product design and analyze the impacts of product design on quality competitiveness, product reliability, and consumer satisfaction in an attempt to provide a foundation for the theory of design management. For this empirical analysis, this study has derived the relevant measurement variables from a survey on 400 Korean manufacturing firms during the period of $August{\sim}October$ 2003. The empirical findings are summarized as follows: First, the determinants of product design are very significantly (at p<0.001) estimated to be the R&D capability, the level of R&D expenditure, the level of innovative activities(5S, TQM, 6Sigma, QC, etc.). This empirical result can support Pawar and Driva(1999)'s two principles by which the performance of product design and product development can be simultaneously evaluated in the context of CE(concurrent engineering) of NPD(newly product development) activities. Second, the hypothesis on the causality: product design${\rightarrow}$quality competitiveness${\rightarrow}$customer satisfaction${\rightarrow}$customer loyalty is very significantly (at p<0.001) accepted. This implies that product design positively affects consumer satisfaction, not directly but indirectly, by influencing quality competitiveness. This empirical result of this study can also support the studies of for example Flynn et al.(1994), Ahire et at.(1996), Afire and Dreyfus(2000) which conclude that design management is a significant determinant of product quality. The aforementioned empirical results are important in the following sense: the empirical result that quality competitiveness plays a bridging role between product design and consumer satisfaction can reconcile the traditional debate between QFD(quality function development) approach asserted by product developers and conjoint analysis maintained by marketers. The first empirical result is related to QFD approach whereas the second empirical result is related to conjoint analysis. At the same time, the empirical results of this study can support the rationale of design integration(DI) of Ettlie(1997), i.e., the coordination of the timing and substance of product development activities performed by the various disciplines and organizational functions of a product's life cycle. Finally, the policy implication (at the corporate level) from the empirical results is that successful design management(DM) requires not only the support of top management but also the removal of communication barriers, (i.e. the adoption of cross-functional teams) so that concurrent engineering(CE), the simultaneous development of product and process designs can assure product development speed, design quality, and market success.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.593-601
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• 2016

This study was carried out to establish an effective marketing strategy based on Importance-Performance Analysis (IPA) of rice-convenience foods. IPA is one of the most efficient and simple methods to evaluate product quality. Data were collected from 652 people (320 males and 332 females) and analyzed by SPSS 19.0. Subjects consumed rice-convenience foods as a snack substitute (19.3%), breakfast (20.7%), lunch (37.4%), dinner (15.2%), and late-night meal (7.4%). The purpose for consumption of rice-convenience foods were as follows: light meal (34.8%), lack of time to prepare meal (42.2%), favorite restaurant is not nearby (2.3%), save money (3.4%), and outdoor activities (9.7%). All attributes about rice-convenience foods were categorized into intrinsic property and extrinsic property. As a result of factor analysis, health, sensibility, and diversity factors were extracted from intrinsic property. In addition, dependence and appearance factors were drawn from extrinsic property. In analyzing the differences between importance and performance, there were significant differences; 16 items in the intrinsic property (P<0.01), and 10 items in the extrinsic property (P<0.001). The IPA matrix is composed of four quadrants, and each represents different strategies; the first, 'keep up the good work', the second, 'possible overkill', the third, 'low priority for management', and the fourth, 'concentrate management'. As a result, factors of rice-convenience foods positioned in the fourth quadrant were 'safety (from food additives, etc.)' and 'price' in the intrinsic property and 'nutrition label' and 'safety of packaging material' in the extrinsic property. They need to be improved immediately. In this study, rice-convenience food factors for continuous maintenance and concentrative improvement were compared by IPA. Based upon the results of this study, it is necessary to develop methods to make efficient use of limited resources and practical marketing strategies.

• Development and Reproduction
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• v.4 no.1
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• pp.67-77
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• 2000

Snailfish usually lives at the bottom of the sea and showed typical retrogressive change with specialized tissue structures of skin and skeletons. In order to obtain the specific genes of snailfish, highly expressed in the body, we made subtracted cDNA library and analyzed 200 clones. Totally 200 clones were obtained and sequenced, and among them 62 clones were turned out to be homologous to the known gene, i.e., thioesterase (9), myosin (8), creatine kinase (7), skeletal alpha-actin (6), parvalbumin b (5), ribosomal protein (5), type I collagen (3), muscle troponin (3), dopamine receptor (2), histatin (2), and heat shock protein (2), cystatin (1), lectin (1), statherin (1), secretory carrier membrane protein (1), keratin type I (1), desmin (1), chloroplast (1), muscle tropomyosin (1), reticulum calcium ATPase (1), ribonucleoprotein (1). The remaining 138 clones were low homologous or non-redundant genes through Genbank search. Especially 5 clones were novel and specifically expressed in the body tissues of Snailfish by in situ hybridization. Therefore, we analysed these 5 clones to identify the C-terminal protein structures and motifs, and partly defined the roles of these proteins in comparison with the expression patterns by in situ hybridization. C9O-77, about 5000 bp, was supposed to be a matrix protein expressed strongly positive in epithelium, myxoid tissue, fibrous tissue and collagenous tissue. C9O-116, about 1500 bp, was supposed to be a transmembrane protein which was weakly expressed in the fibrous tissue, epithelium tissue, and myxoid tissue, but strong in muscle tissue. C9O-130, about 1200 bp, was supposed to be an intracytoplasmic molecule usually in the epithelial cells. C9O-161, about 2000 bp, was weakly expressed in epithelium, muscle tissue and myxoid tissue, but specially strong in epithelium. C9O-171, about 1000 bp, was supposed to be a transcription factor containing zinc finger like domain, which was intensely expressed in the epithelium, muscle tissue, fibrous tissue, and in collagenous tissue.