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Biodistribution of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine in Tumor Bearing Rats: A Comparison Study with L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine (종양 이식 백서에서 3-[$^{131}I$iodo-O-methyl-L-${\alpha}$-methyltyrosine의 체내 동태 연구: L-3-[$^{131}I$iodo-${\alpha}$-methyltyrosine와 비교)

  • Choi, Chang-Woon;Yang, Seung-Dae;Woo, Kwang-Sun;Chung, Wee-Sup;Lim, Soo-Jung;Suh, Yong-Sup;Chun, Kwon-Soo;Ahn, Soon-Hyuk;Lee, Jong-Doo;Hong, Sung-Woon;Lim, Sang-Moo
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.3
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    • pp.290-297
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    • 1998
  • Purpose : The aim of this study was to evaluate the feasibility of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine ([$^{131}I$]OMIMT) as an agent for tumor image. Materials and Methods : After synthesis of 4-O-methyl-L-${\alpha}$-methyltyrosine (OMAMT), OMAMT was labeled with [$^{131}I$] using Iodogen method. In vitro cellular uptake study was performed using 9 L gliosarcoma cells at various time points upto 4 hr. The biodistribution (five rats implanted with the 9 L gliosar-coma cells per group) was evaluated at 30 min, 2 hr, 24 hr after iv injection of 3.7 MBq [$^{131}I$]OMIMT or L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine [$^{131}I$]IMT). Gamma camera images were obtained at 30 min, 2 hr and 24 hr. Results: [$^{131}I$]OMIMT uptake was 3.3 times and 2.5 times higher than [$^{131}I$]IMT uptake at 30 min and 60 min, respectively and same after 2 hr in in vitro study using 9L gliosarcoma cells. Maximum accumulation in tumor occurred at 30 min for both [$^{131}I$]OMIMT and [$^{131}I$]IMT in tumor bearing rats. The tumor uptake of [$^{131}I$]OMIMT was significantly higher than that of [$^{131}I$]IMT at early time point studied ($3.74{\pm}0.48$ vs $0.38{\pm}0.17%$ ID/g at 30 min and $2.40{\pm}0.17$ vs $0.24{\pm}0.03%$ ID/g at 2 hr, respectively, p<0.01). However, the tumor uptake of both radiolabels were not significantly different at 24 hr ($0.04{\pm}0.01$ vs $0.05{\pm}0.01%$ ID/g). Tumor was visualized as early as at 30 min in gamma camera images. Conclusion: These data suggested that [$^{131}I$]OMIMT might be a useful tumor imaging agent and has more advantage for the tumor imaging compared to [$^{131}I$]IMT

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The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 2007
  • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

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The Role of c-Jun N-terminal Kinase in the Radiation-Induced Lung Fibrosis (방사선에 의한 폐 섬유화증에서 c-Jun N-terminal Kinase(JNK)의 역할)

  • Uh, Soo-Taek;Hong, Ki-Young;Lee, Young-Mok;Kim, Ki-Up;Kim, Do-Jin;Moon, Seung-Hyuk;Kim, Yong-Hoon;Park, Choon-Sik;Yeom, Uk;Kim, Eun-Suk;Choi, Doo-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.450-461
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    • 2001
  • Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

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Antibacterial and Antioxidative Activities of Quercus acutissima Carruth Leaf Extracts and Isolation of Active Ingredients (상수리나무 잎 추출물의 항균 및 항산화 활성과 활성 물질 분리)

  • Park, Soo-Nam;Kim, So-I;Ahn, You-Jin;Kim, Eun-Hee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.35 no.2
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    • pp.159-169
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    • 2009
  • In this study, the antibacterial activity, antioxidative effects, inhibitory effects on tyrosinase, inhibitory effects on elastase, and components of Quercus acutissima Carruth leaf extracts were investigated. MIC values of ethyl acetate fraction from Q. acutissima Carruth leaf on P. acnes, S. aureus, P. ovale, and E. coli were 0.13 %, 0.25 %, 0.13 % and 0.25 %, respectively. The results showed that the antibacterial activity of the ethyl acetate fraction was the highest in the S. aureus, P. acnes, and P. ovale. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity ($FSC_{50}$) of extract/fractions of Q. acutissima Carruth. leaf was in the order: 50 % ethanol extract (12.13 ${\mu}g/mL$) < ethyl acetate fraction (7.07 ${\mu}g/mL$) < deglycosylated flavonoid aglycone fraction (6.20 ${\mu}g/mL$). Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of some Q. acutissima Carruth leaf extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activity was 50 % ethanol extract ($OSC_{50}$, 1.81 ${\mu}g/mL$) < ethyl acetate fraction (1.70 ${\mu}g/mL$) < deglycosylated flavonoid aglycone fraction (0.70 ${\mu}g/mL$). Deglycosylated flavonoid aglycone fraction showed the most prominent scavenging activity. The protective effects of extract/fractions of Q. acutissima Carruth leaf on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The Q. acutissima Carruth leaf extracts suppressed photohemolysis in a concentration dependent manner, particularly deglycosylated flavonoid aglycone fraction exhibited the most prominent celluar protective effect (${\tau}50$, 220.00 min at 25 ${\mu}g/mL$). Aglycone fractions obtained from the deglycosylation reaction of ethyl acetate fraction among the Q. acutissima Carruth leaf extracts, showed 3 bands (QA 1, QA2 and QA3) on TLC. TLC chromatogram of ethyl acetate fraction of Q. Carruth. leaf extract revealed 4 bands (QA 1 ${\sim}$ QA 4), Among them, kaempferol (QA 1), quercetin (QA 2), and gallic acid (QA 3) were identified. The inhibitory effect ($IC_{50}$) of aglycone fraction on tyrosinase was 65.7 ${\mu}g/mL$. The inhibitory effect ($IC_{50}$) of aglycone fraction on elastase was 24.50 ${\mu}g/mL$. These results indicate that extract/fractions of Q. acutissima Carruth. can functionized as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS. Extract/fractions of Q. acutissima Corruth can be applicable to new functional cosmetics for antioxidant, antiaging, antibacterial activity.

Tuberculin Skin Test and Plasma Prostaglandin $E_2$ In Patients of New and Intractable Pulmonary Tuberculosis (초치료 및 난치 폐결핵 환자의 투베르쿨린 피부검사와 혈장 Prostaglandin $E_2$)

  • Kim, Ji-Hong;Choi, In-Hwan;Kim, Mee-Ae;Shin, Chul-Shik;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.669-676
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    • 1995
  • Background: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prostaglandin(PG), especially PG $E_2$, is involved in cellular immunosuppression. It is known that the PG $E_2$ is suppressed by indomethacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG $E_2$ levels. Method: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG $E_2$, levels with radioimmunoassay. Results: 1) There was no significant difference in the plasma PG $E_2$ levels among A group(far advanced and positive TST reaction cases, n=10, $11.22{\pm}2.86\;pg/ml$), B group(minimal and negative TST reaction cases, n=9, $11.35{\pm}2.20$) and C group(far advanced and positive TST reaction cases, n=7, $11.11{\pm}2.30$) in the new cases(p>0.05). 2) There was no significant difference in the plasma PG $E_2$ levels between positive(n=10, $9.25{\pm}2.21$) and negative(n=10, $8.25{\pm}1.13$) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG $E_2$ levels between new(n=26, $11.35{\pm}2.41$) and intractable(n=20, $8.75{\pm}1.78$) groups, the intractable group had significi- andy lower plasma PG $E_2$ levels(p<0.05). 4) There was no significant difference in the plasma PG $E_2$ levels between negative(n=19, $9.88{\pm}2.43$) and positive(n=27, $10.46{\pm}2.56$) groups by TST(p>0.05). 5) There was no significant difference in the plasma PG $E_2$ levels between male(n=32, $10.07{\pm}2.44$) and female(n=14, $10.56{\pm}2.70$)(p>0.05). 6) There was no significant difference in the plasma PG $E_2$ levels among 2nd(n=5, $10.21{\pm}2.86$), 3rd(n=9, $9.97{\pm}2.47$), 4th(n=13, $11.35{\pm}2.33$) and 5th(n=19, $9.57{\pm}2.48$) decades(p>0.05). 7) There was no significant correlation between the induration sizes of the TST and the plasma PG $E_2$ levels(r=0.054, p>0.05). Conclusion: From the above results, the plasma PG $E_2$ levels of intractable group are not higher as the authors had expected. There was no significant difference in the plasma PG $E_2$ levels by the lesion sizes of plain chest roentgenogram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary tuberculosis patients.

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Changes in Immunogenicity of Preserved Aortic Allograft (보존된 동종동맥편 조직의 면역성 변화에 관한 연구)

  • 전예지;박영훈;강영선;최희숙;임창영
    • Journal of Chest Surgery
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    • v.29 no.11
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    • pp.1173-1181
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    • 1996
  • The causes of degenerative changes in allograft cardiac valves are not well known to this day. Today's preserved allografts possess highly viable endothelial cells and degeneration of allografts can be facilitated by immune reaction which may be mediated by these viable cells. To test the antigenicity of endothelial cells, pieces from aortic wall were obtained from fresh and cryo-preserved rat allograft. Timings of sampling were prior to sterilization, after sterilization, after 1, 2, 7, 14 days of fresh preservation and cryopreservation. Endothelial cells were tested by immunohistochemical methods using monoclonal antibodies to MHC class I(MRC OX-18), class II(MRC OX-6) and ICAM-1 antigens. After transplantation of each group of aortic allograft at the subcutaneous layers of rats, population of CD4$^{+}$ T cell and CD8$^{+}$ T cell were analyzed with monoclonal antibodies after 1, 2, 3, 4, 6 and 8 weeks. MHC class I expression was 23.95% before preservation and increased to 35.53~48.08% after preservation(p=0.0183). MHC Class II expression was 9.72% before preservation and 10.13~13.39% after preservation(P=0.1599). ICAM-1 expression was 15.02% before preservation and increased to 19.85~35.33% after preservation(P=0.001). The proportion of CD4$^{+}$ T-cell was 42.13% before transplantation. And this was 49.23~36.8% after transplantation in No treat group (p=0.955), decreased to 29.56~32.80% in other group(p=0.0001~0.008). In all the groups, the proportion of CD8$^{+}$ T-cell increased from 25.57% before transplantation to 42.32~58.92% after transplantation(p=0.000l~0.0002). The CD4$^{+}$/CD8$^{+}$ ratio decreased from 1.22~2.28 at first week to 0.47~0.95 at eighth week(p=0.0001). The results revealed that the expression of MHC class I and ICAM-1 in aortic allograft endothelium were increased but that of MHC class II were not changed, despite the different method of preservation. During 8 weeks after transplantation of aortic allograft, the subpopulations of CD4$^{+}$ T cell were not changed or only slightly decreased but those of CD8$^{+}$ T cell were progressively increased.ely increased.

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Antioxidative Activity and Component Analysis of Psidium guajava Leaf Extracts (구아바 잎 추출물의 항산화 활성과 성분 분석)

  • Yang, Hee-Jung;Kim, Eun-Hee;Park, Soo-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.34 no.3
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    • pp.233-244
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    • 2008
  • In this study, the antioxidative effects, inhibitory effects on elastase and tyrosinase, and component analysis of Psidium guajava leaf extracts were investigated. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activities $(FSC_{50})$ of extract/fractions of Psidium guajava leaf were in the order: 50% ethanol extract $(7.05{\mu}g/mL)$ < ethyl acetate fraction $(3.36{\mu}g/mL)$ < deglycosylated flavonoid aglycone fraction $(3.24{\mu}g/mL)$. Reactive oxygen species (ROS) scavenging activities $(OSC_{50})$ of some Psidium guajava leaf extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activities were 50% ethanol extract $(OSC_{50},\;2.17{\mu}g/mL)$ < ethyl acetate fraction $(0.64{\mu}g/mL)$ < deglycosylated flavonoid aglycone fraction $(3.39{\mu}g/mL)$. Aglycone fraction showed the most prominent ROS scavenging activity. The protective effects of extract/fractions of Psidium guajava leaf on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The Psidium guajava leaf extracts suppressed photohemolysis in a concentration dependent manner $(1{\sim}10{\mu}g/mL)$, particularly deglycosylated flavonoid aglycone fraction exhibited the most prominent celluar protective effect ${\tau}_{50}\;107.5min\;at\;1{\mu}g/mL)$. Aglycone fraction obtained from the deglycosylation reaction of ethyl acetate fraction among the Psidium guajava leaf extracts, showed 1 band in TLC and 1 peak in HPLC experiments (360 nm). One component was identified as quercetin. TLC chromatogram of ethyl acetate fraction of Psidium guajava leaf extract revealed 5 bands and HPLC chromatogram showed 5 peaks, which were identified as quercetin 3-O-gentobioside (10.32%) , quercetin 3-O-${\beta}$-D-glucoside (isoquercitin, 13.30%), quercetin 3-O-${\beta}$-D-galactoside (hyperin, 11.34%), quercetin 3-O-${\alpha}$-L-arabinoside (guajavarin, 19.70%), quercetin 3-O-${\beta}$-L-rhamnoside (quercitrin, 45.33%) in the order of elution time. The inhibitory effect of Psidium guajava leaf extracts on tyrosinase were investigated to assess their whitening efficacy. Finally, their anti-elastase activities were measured to predict the anti-wrinkle efficacy in the human skin. Inhibitory effects $(IC_{50})$ on tyrosinase of some Psidium guajava leaf extracts was 50% ethanol extract $(149.67{\mu}g/mL)$ < ethylacetate fraction $(30.67{\mu}g/mL)$ < deglycosylated aglycone fraction $(17.10{\mu}g/mL)$. Inhibitory effects $(IC_{50})$ on elastase of some Psidium guajava leaf extracts was 50% ethanol extract $(6.60{\mu}g/mL)$ < deglycosylated aglycone fraction $(5.66{\mu}g/mL)$ < ethylacetate fraction $(3.44{\mu}g/mL)$. These results indicate that extract/fractions of Psidium guajava leaf can function as antioxidants in bioloigcal systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS. And component analysis of Psidium guajava leaf extract and inhibitory activity on elastase of the aglycone fraction could be applicable to new functional cosmetics for smoothing wrinkles.

The Effect of Price Discount Rate According to Brand Loyalty on Consumer's Acquisition Value and Transaction Value (브랜드애호도에 따른 가격할인율의 차이가 소비자의 획득가치와 거래가치에 미치는 영향)

  • Kim, Young-Ei;Kim, Jae-Yeong;Shin, Chang-Nag
    • Journal of Global Scholars of Marketing Science
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    • v.17 no.4
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    • pp.247-269
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    • 2007
  • In recent years, one of the major reasons for the fierce competition amongst firms is that they strive to increase their own market shares and customer acquisition rate in the same market with similar and apparently undifferentiated products in terms of quality and perceived benefit. Because of this change in recent marketing environment, the differentiated after-sales service and diversified promotion strategies have become more important to gain competitive advantage. Price promotion is the favorite strategy that most retailers use to achieve short-term sales increase, induce consumer's brand switch, in troduce new product into market, and so forth. However, if marketers apply or copy an identical price promotion strategy without considering the characteristic differences in product and consumer preference, it will cause serious problems because discounted price itself could make people skeptical about product quality, and the changes of perceived value might appear differently depending on other factors such as consumer involvement or brand attitude. Previous studies showed that price promotion would certainly increase sales, and the discounted price compared to regular price would enhance the consumer's perceived values. On the other hand, discounted price itself could make people depreciate or skeptical about product quality, and reduce the consumers' positivity bias because consumers might be unsure whether the current price promotion is the retailer's best price offer. Moreover, we cannot say that discounted price absolutely enhances the consumer's perceived values regardless of product category and purchase situations. That is, the factors that affect consumers' value perceptions and buying behavior are so diverse in reality that the results of studies on the same dependent variable come out differently depending on what variable was used or how experiment conditions were designed. Majority of previous researches on the effect of price-comparison advertising have used consumers' buying behavior as dependent variable. In order to figure out consumers' buying behavior theoretically, analysis of value perceptions which influence buying intentions is needed. In addition, they did not combined the independent variables such as brand loyalty and price discount rate together. For this reason, this paper tried to examine the moderating effect of brand loyalty on relationship between the different levels of discounting rate and buyers' value perception. And we provided with theoretical and managerial implications that marketers need to consider such variables as product attributes, brand loyalty, and consumer involvement at the same time, and then establish a differentiated pricing strategy case by case in order to enhance consumer's perceived values properl. Three research concepts were used in our study and each concept based on past researches was defined. The perceived acquisition value in this study was defined as the perceived net gains associated with the products or services acquired. That is, the perceived acquisition value of the product will be positively influenced by the benefits buyers believe they are getting by acquiring and using the product, and negatively influenced by the money given up to acquire the product. And the perceived transaction value was defined as the perception of psychological satisfaction or pleasure obtained from taking advantage of the financial terms of the price deal. Lastly, the brand loyalty was defined as favorable attitude towards a purchased product. Thus, a consumer loyal to a brand has an emotional attachment to the brand or firm. Repeat purchasers continue to buy the same brand even though they do not have an emotional attachment to it. We assumed that if the degree of brand loyalty is high, the perceived acquisition value and the perceived transaction value will increase when higher discount rate is provided. But we found that there are no significant differences in values between two different discount rates as a result of empirical analysis. It means that price reduction did not affect consumer's brand choice significantly because the perceived sacrifice decreased only a little, and customers are satisfied with product's benefits when brand loyalty is high. From the result, we confirmed that consumers with high degree of brand loyalty to a specific product are less sensitive to price change. Thus, using price promotion strategy to merely expect sale increase is not recommendable. Instead of discounting price, marketers need to strengthen consumers' brand loyalty and maintain the skimming strategy. On the contrary, when the degree of brand loyalty is low, the perceived acquisition value and the perceived transaction value decreased significantly when higher discount rate is provided. Generally brands that are considered inferior might be able to draw attention away from the quality of the product by making consumers focus more on the sacrifice component of price. But considering the fact that consumers with low degree of brand loyalty are known to be unsatisfied with product's benefits and have relatively negative brand attitude, bigger price reduction offered in experiment condition of this paper made consumers depreciate product's quality and benefit more and more, and consumer's psychological perceived sacrifice increased while perceived values decreased accordingly. We infer that, in the case of inferior brand, a drastic price-cut or frequent price promotion may increase consumers' uncertainty about overall components of product. Therefore, it appears that reinforcing the augmented product such as after-sale service, delivery and giving credit which is one of the levels consisting of product would be more effective in reality. This will be better rather than competing with product that holds high brand loyalty by reducing sale price. Although this study tried to examine the moderating effect of brand loyalty on relationship between the different levels of discounting rate and buyers' value perception, there are several limitations. This study was conducted in controlled conditions where the high involvement product and two different levels of discount rate were applied. Given the presence of low involvement product, when both pieces of information are available, it is likely that the results we have reported here may have been different. Thus, this research results explain only the specific situation. Second, the sample selected in this study was university students in their twenties, so we cannot say that the results are firmly effective to all generations. Future research that manipulates the level of discount along with the consumer involvement might lead to a more robust understanding of the effects various discount rate. And, we used a cellular phone as a product stimulus, so it would be very interesting to analyze the result when the product stimulus is an intangible product such as service. It could be also valuable to analyze whether the change of perceived value affects consumers' final buying behavior positively or negatively.

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The Value of Interleukin-12 as an Activity Marker of Pulmonary Sarcoidosis (폐유육종증의 활동성 지표로서 IL-12의 효용성에 관한 연구)

  • Kim, Tae-Hyung;Jeon, Yong-Gam;Shim, Tae-Sun;Lim, Chae-Man;Koh, Yun-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.215-228
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    • 1999
  • Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

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Activation of NF-${\kappa}B$ in Lung Cancer Cell Lines in Basal and TNF-${\alpha}$ Stimulated States (폐암 세포에서 기저 상태와 TNF-${\alpha}$ 자극 시 NF-${\kappa}B$의 활성화)

  • HwangBo, Bin;Lee, Seung-Hee;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.485-496
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    • 2002
  • Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.