• Title/Summary/Keyword: protein-protein interaction

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Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

Changes of pH, Meat Color, Cooking Loss, Shear Force and Sensory Evaluation on Hanwoo Meat Fed with Supplemental Fig Fermentation during Storage Period (무화과 발효물을 급여한 한우고기의 저장기간 중 pH, 육색, 가열감량, 전단력 및 관능평가의 변화)

  • Kook, Kil;Kim, Kwang-Hyun
    • Food Science of Animal Resources
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    • v.22 no.4
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    • pp.289-293
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    • 2002
  • This study was conducted to investigate changes of pH, meat color, cooking loss, shear force and sensory evaluation on Hanwoo meat fed with supplemental fig fermentation(SFF) during storage period. A total of 10 Hanwoo bulls were subjected to one of two treatment diets (control and 10% SFF) from live weight of 400kg far 6 months. After slaughter, longissimus muscles were removed, zipper-wrapped and stored at 4$\^{C}$ for 21 days. The pH, meat color, cooking loss, shear force and sensory evaluation of the samples were measured at 1, 3, 9, 15, 21 days of storage. There were no differences in pH, meat objective color(Hunter L, a and b) and cooking loss (%) of longissimus muscles between control and SFF treatment during storage. Shear force values of longissimus muscle from SFF treatment showed lower level in 1, 3 and 9 days and tended to decrease during storage. No differences in odor and appearance of sensory evaluation were observed between control and SFF treatment during storage. The taste induced by SFF was increased(f<0.05) at 1, 3 and 9 days of storage. These results indicate that the SFF may improve meat quality of Hanwoo during storage.

Effects of Three Dietary Growth Hormones on Growth Performance and Lysozyme Activity in Juvenile Olive Flounder, Paralichthys olivaceus

  • Lee, Seung-Hyung;Yoo, Gwang-Yeol;Park, Gun-Jun;Kim, Young-Chul;Lee, Jun-Ho;Bai, Sung-Chul C.
    • Fisheries and Aquatic Sciences
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    • v.11 no.4
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    • pp.183-189
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    • 2008
  • In this study, tests were conducted to investigate the effects of three dietary growth hormones, administered in various amounts, on the growth performance and lysozyme activity in juvenile olive flounder, Paralichthys olivaceus. Three dietary growth hormones, recombinant human growth hormone (rHGH), recombinant bovine somatotropin A (rBST A) and recombinant bovine somatotropin B (rBST B) were tested at three different supplemental levels (10, 20 or 40 mg/kg body weight per week) by a $3{\times}3$ factorial design and a complete randomized design in comparison to a control group. Fish were fed one of the ten experimental diets (control, $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$, rBST $B_{10}$, rBST $B_{20}$ and rBST $B_{40}$) for 6 weeks and afterward were analyzed for growth performance by measuring weight gain (WG), feed efficiency (FE), specific growth rate (SGR) and protein efficiency ratio (PER). Based on the factorial design analysis, fish fed rHGH diets demonstrated significantly higher growth performance than fish fed rBST A or rBST B diets. However there were no significant differences in WG, FE, SGR and PER between fish fed rBST A and rBST B diets. Neither hormone level nor the interaction between the different hormones and their various levels had a significant effect on WG, FE, SGR, PER, lysozyme activity or whole-body proximate composition. A complete randomized design analysis confirmed fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$, rBST $B_{20}$ and rBST $B_{40}$ diets for 6 weeks showed higher WG than fish fed the control diet (P<0.05). A higher FE was observed in fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{20}$ and rBST $A_{40}$ diets in comparison to fish fed the control diet. Fish fed all graded rHGH, rBST A and rBST B supplemented diets showed a higher SGR than fish fed the control diet. Regarding PER, fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$ and rBST $B_{20}$ diets were higher than fish fed the control diet. Furthermore, the lysozyme activity of fish fed a diet of $rHGH_{20}$ was significantly higher than that of fish fed any other diet. The results measuring the growth and development of the fish clearly suggest the biopotency of dietary rHGH could be higher than those of both dietary rBST A and rBST B. Further implied is the probability that within the range of 10 to 40 mg/kg BW/week the dietary growth hormones could accelerate growth performance, and that 20 mg rHGH/kg BW/week could possibly enhance lysozyme activity in juvenile olive flounder, Paralichthys olivaceus.

The expression patterns of RANKL and OPG in murine tooth eruption (치아발육시기에서의 RANKL 및 OPG의 발현 양상)

  • Hwang, Kyung-Mun;Kim, Eun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.33 no.2
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    • pp.290-303
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    • 2006
  • Tooth eruption is a complex and tightly regulated process that involves cells of the tooth organ and the surrounding alveolus. Osteoclast precursors must be recruited into the dental follicle prior to the onset of eruption. This function of dental follicle may be regarded as the ability of bone remodeling characterized by the interaction of osteoclasts and osteoblasts. This is because tooth eruption is a localized event in which many of the genes required for eruption are expressed in the dental follicle. RANKL is a membrane-bound protein that is a member of the TNF ligand family. which is present on bone marrow stromal cells and osteoblasts, and induces osteoclast formation and activation from precursor cell. The biologic effect of RANKL is inhibited by OPG and, in bone, the relative ratio of RANKL and OPG modulates osteoclastogenesis. To evaluate the roles of RANKL and OPG in tooth eruption and the relations with the expression pattern of Runx2, in situ hybridization was performed with mandibles of mice at postnatal stage 1, 3, 5, 7, 9 and 11. mRNA of RANKL, OPG, and Runx2 are expressed in dental follicle and surrounding tissue from P1 to 11. To determine the sites of osteoclastic activity during tooth eruption, mandibles were dissected. Peak osteoclastic activity in alveolar bone along the occlusal and basal regions was observed from P5 to 9, with osteoclasts in these regions being large and strongly TRAP-positive The specific spatio-temporal expression patterns of RANKL, OPG, and Runx2 in our study suggest that tooth eruption could be progressed through the interactions of molecular signaling among dental follicle, dental organ and alveolar bone, furthermore it means that dental follicle is quite important in tooth eruption In addition, it indicates that these genes (RANKL, OPG, and Runx2) play critical roles in tooth eruption.

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Effects of Elastic Band Exercise on Body Composition, Blood lipids and AMPK in the Elderly Women (탄력밴드 운동이 여성노인의 체조성, 혈중지질 및 AMPK에 미치는 영향)

  • Choi, Mi-Ri-Na;Ha, Soo-Min;Kim, Do-Yeon
    • Journal of the Korean Applied Science and Technology
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    • v.36 no.3
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    • pp.995-1007
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    • 2019
  • The purpose of this study was to investigate the effects of 12-week elastic band exercise on body composition, blood lipids and AMPK in 24 elderly female volunteers aged 65-75 years, and they were divided into the combined exercise group(n=12) and the control group(n=12). The elastic band exercise method was to do exercise 3 times a week for 60 minutes per session, 1-4 weeks for low intensity of OMNI-RES 3-4, 5-8 weeks for medium intensity of OMNI-RES 5-6, 9-12 weeks for OMNI-RES 7-8 of high intensity. In order to compare the differences in the groups before and after the elastic band exercise, two-way repeated measures ANOVA was used to verify the interaction between group and time. The difference in the groups of the measured data was paired t-test, the difference between the groups was paired independent t-test, and analysis of covariance ANCOVA was performed to minimize the inter-group error. The statistical significance level of each item was set to .05. As a result, body fat percentage of exercise group significantly decreased (p<.05), and skeletal muscle volume was significantly increased (p<.01). TC, TG and LDL-C were not significantly different between the exercise and control groups, and HDL-C was significantly decreased in the control group (p<.05). AMPK was significantly decreased in the exercise group (p<.001), but there was no significant difference in the control group. According to the covariance analysis to minimize the error of difference between the pre-exercise groups (p<.05), there was significant difference in AMPK of groups after exercise. These results suggest that the 12-week elastic band exercise has a positive effect on the body composition and AMPK of the elderly women.

Roles of the Insulin-like Growth Factor System in the Reproductive Function;Uterine Connection (Insulin-like Growth Factor Systems의 생식기능에서의 역할;자궁편)

  • Lee, Chul-Young
    • 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.

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Studies on Dry Matter Yields , Chemical Composition and Net Energy Accumulation in Three Leading Temperate Grass Species I. Influence of meteorolgical factors on the dry matter productivity and net energy value under different cutting management (주요 북방형목초의 건물수량 , 화학성분 및 Net Energy 축적에 관한 연구 I. 기상환경 및 예취관리에 따른 건물 및 에너지 생산성 변화)

  • F. Muhlschlegel;G. Voigtlander
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.6 no.2
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    • pp.103-110
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    • 1986
  • The experiments were carried out to study the influence of meteorological factors and cutting management on dry matter accumulation and net energy value in orchardgrass (Dactlylis glomerata L.) cv. Potomac and Baraula, perennial ryegrass (Lolium perenne L.) cv. Reveille and Semperweide and meadow fescue (Festuca pratensis Huds.) cv. Cosmos 11 and N.F.G.. The field trials were designed as a split plot design with three cutting regimes of 6-7 cuts at grazing stage, 4-5 cuts at silage stage and 3 cuts at hat stage in Korea and West Germany from 1975 to 1979. The results obtained are summarized as follows: 1. Productivity of orchardgrass, perennial ryegrass and meadow fescue were mainly affected by cutting systems and meteorological factors, especially air temperature, rainfalls, solar radiation and their interactions. In West Germany, cutting frequency was to be found asan most important factor influenced to dry matter yield and net energy value. 2. Orchardgrass, taken as average of all experimental sites in Korea, produced high yield of 875 kg/10 a in dry matter, which was as much as 32% and 27% higher than those of perennial ryegrass and meadow fescue, respectively. The annual dry matter yields of orchardgrass from 1976 to 1977 were shown a little variation. Dry matter yields in Freising and Braunschweig in West Germany were increased in all grass species continuously. 3. Orchardgrass, perennial ryegrass and meadow fescue showed different response to cutting frequency. The highest dry matter yields were found under 3 cuts at hay stage for orchardgrass and 4-5 cuts at silage stage for perennial ryegrass and meadow fescue. In West Germany, dry matter yields, as average of all grass species under different cutting systems, were 1326 kg, 1175 kg and 1098 kg/10a for 3 cuts, 4-5 cuts and 6-7 cuts, respectively. 4. Chemical composition and net energy concentration of temperate grasses were influenced by cutting managements. The highest yields of digestible crude protein were obtained under 6-7 cuts at grazing stage both in Korea and West Germany. In net energy yields, 3 cutting system produced the highest yield with 694 (orchardgrass), 665 (perennial ryegrass) an 623 kStE/10 a (meadow fescue). However, frequent cutting at grazing and silage stage produced higher yields than 3 cuts at hay stage in Cheju, Suweon and Taekwalyong.

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The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-$\beta$ from Monocytes of Balb/C Mice (Balb/C mouse의 폐장대식세포에서 유리규산 자극에 의한 Proinflammatory Cytokine과 TGF-$\beta$의 생성 및 상관관계)

  • Ki, Shin-Young;Kim, Eun-Young;Kim, Mi-Ho;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.823-834
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    • 1998
  • Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

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