• Title/Summary/Keyword: Yoon Yong

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Transformation of Adult Mesenchymal Stem Cells into Cardiomyocytes with 5-azacytidine: Isolated from the Adipose Tissues of Rat (성체 백서의 지방조직에서 추출한 중간엽 줄기세포의 5-azacytidine을 이용한 심근세포 분화 유도)

  • Choe Ju-Won;Kim Yong-In;Oh Tae-Yun;Cho Dai-Yoon;Sohn Dong-Suep;Lee Tae-Jin
    • Journal of Chest Surgery
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    • v.39 no.7 s.264
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    • pp.511-519
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    • 2006
  • Background: Loss of cardiomyocytes in the myocardial infarction leads to regional contractile dysfunction, and necrotized cardiomyocytes in infracted ventricular tissues are progressively replaced by fibroblasts forming scar tissue. Although cardiomyoplasty, or implantation of ventricular assist device or artificial heart was tried in refractory heart failure, the cardiac transplantation was the only therapeutic modality because these other therapeutic strategies were not permanent. Cell transplantation is tried instead of cardiac transplantation, especially bone marrow is the most popular donated organ. But because bone marrow aspiration procedure is invasive and painful, and it had the fewer amounts of cellular population, the adipose tissue is recommended for harvesting of mesenchymal stem cells. Material and Method: After adipose tissues were extracted from abdominal subcutaneous adipose tissue and intra-abdominal adipose tissue individually, the cellular components were obtained by same method. These cellular components were tried to transformation with the various titers of 5-azacytidine to descript the appropriate concentration of 5-azacytidine and possibility of transformation ability of adipose tissue. Group 1 is abdominal subcutaneous adipose tissue and Group 2 is intra-abdominal adipose tissue-retroperitoneal adipose tissue and omentum. Cellular components were extracted by collagenase and $NH_4Cl$ et al, and these components were cultured by non-induction media - DMEM media containing 10% FBS and inducted by none, $3{\mu}mol/L,\;6{\mu}mol/L,\;and\;9{\mu}mol/L$ 5-azacytidine after the 1st and 2nd subculture. After 4 weeks incubation, tile cell blocks were made, immunostaining was done with the antibodies of CD34, heavy myosin chain, troponin T, and SMA. Result: Immunostaining of the transformed cells for troponin T was positive in the $6{\mu}mol/L\;&\;9{\mu}mol/L$ 5-azacytidine of Group 1 & 2, but CD34 and heavy myosin chain antibodies were negative and SMA antibody was positive in the $3{\mu}mol/L\;&\;6{\mu}mol/L$ 5-azacytidne of Group 2. Conclusion: These observations confirm that adult mesenchymal stem cells isolated from the abdominal subcutaneous adipose tissues and intra-abdominal adipose tissues can be chemically transformed into cardiomyocytes. This can potentially be a source of autologous cells for myocardial repair.

Quantitative Analysis of Carbohydrate, Protein, and Oil Contents of Korean Foods Using Near-Infrared Reflectance Spectroscopy (근적외 분광분석법을 이용한 국내 유통 식품 함유 탄수화물, 단백질 및 지방의 정량 분석)

  • Song, Lee-Seul;Kim, Young-Hak;Kim, Gi-Ppeum;Ahn, Kyung-Geun;Hwang, Young-Sun;Kang, In-Kyu;Yoon, Sung-Won;Lee, Junsoo;Shin, Ki-Yong;Lee, Woo-Young;Cho, Young Sook;Choung, Myoung-Gun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.425-430
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    • 2014
  • Foods contain various nutrients such as carbohydrates, protein, oil, vitamins, and minerals. Among them, carbohydrates, protein, and oil are the main constituents of foods. Usually, these constituents are analyzed by the Kjeldahl and Soxhlet method and so on. However, these analytical methods are complex, costly, and time-consuming. Thus, this study aimed to rapidly and effectively analyze carbohydrate, protein, and oil contents with near-infrared reflectance spectroscopy (NIRS). A total of 517 food samples were measured within the wavelength range of 400 to 2,500 nm. Exactly 412 food calibration samples and 162 validation samples were used for NIRS equation development and validation, respectively. In the NIRS equation of carbohydrates, the most accurate equation was obtained under 1, 4, 5, 1 (1st derivative, 4 nm gap, 5 points smoothing, and 1 point second smoothing) math treatment conditions using the weighted MSC (multiplicative scatter correction) scatter correction method with MPLS (modified partial least square) regression. In the case of protein and oil, the best equation were obtained under 2, 5, 5, 3 and 1, 1, 1, 1 conditions, respectively, using standard MSC and standard normal variate only scatter correction methods with MPLS regression. Calibrations of these NIRS equations showed a very high coefficient of determination in calibration ($R^2$: carbohydrates, 0.971; protein, 0.974; oil, 0.937) and low standard error of calibration (carbohydrates, 4.066; protein, 1.080; oil, 1.890). Optimal equation conditions were applied to a validation set of 162 samples. Validation results of these NIRS equations showed a very high coefficient of determination in prediction ($r^2$: carbohydrates, 0.987; protein, 0.970; oil, 0.947) and low standard error of prediction (carbohydrates, 2.515; protein, 1.144; oil, 1.370). Therefore, these NIRS equations can be applicable for determination of carbohydrates, proteins, and oil contents in various foods.

The Factors Affecting on the Franchisor's Performance and Its Intention of Recontracting with Franchisees : Focused on the Chinese Franchise Market (프랜차이즈 본부의 성과 및 재계약의도에 영향을 미치는 요인들에 관한 연구 : 중국프랜차이즈 시장을 중심으로)

  • Shuai, Su;Seo, Sang-Yun;Lee, Hoon-Yong
    • Journal of Distribution Research
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    • v.17 no.3
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    • pp.1-24
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    • 2012
  • Franchises have recently emerged as the most rapidly expanding industry positioned to create a large impact in the domestic economic. The Chinese franchise industry developed rapidly in the period prior and subsequent to WTO accession with more than 50% of new franchises brands emerging since 2000. M&A transactions in the Chinese franchise industry have progressed actively. In the period from 2005-2007, due to the wholesale and retail market opening in accordance with the guidelines laid forth within the MOU by the WTO the Chinese franchise market is now the largest market in the world all despite a short history of only 20 years. The amount of franchise market research on China is disproportional to its current size and development potential. Beginning in the 1990s, market research conducted by the International Franchise Association focused on emerging markets in Eastern Europe and China. While the research dealt with the Chinese investment environment, it insufficiently explained the market region and cultural environment. The purpose of this research is (i) to investigate the determinants of the performance of franchise systems in China and (ii) new contract renewals based on performance factors. This study will complement existing research in terms of the franchisee perspective. This study may also prove of the benefit to the franchise companies entering the Chinese franchise market enabling them to develop an effective strategy. This study shows that support, incentives, and system standardization by franchisor yielded a positive effect on management performance. This is consistent with previous studies by Shin (2000) and Kim (2008) targeting Korean franchises. Therefore, in the Chinese market, the franchisor must focus on support, incentives, and system standardization rather than concentrate only on the recruitment of franchisees in order to improve revenue. Hypotheses regarding franchisor control have been dismissed in existing research, in the opinion of this study, due to their complexity and inability to control the merchant as a one-kind-assessment-standard. Our findings show that the franchisees' financial condition, management ability and entrepreneurial spirit, among franchisee's characteristics, have a positive effect on franchisor's business performance and satisfaction for the franchisee. This is consistent with previous studies on headquarters' management performance of Lussier (1996), Heo and Jang (2008), and franchisees' financial condition, management ability and entrepreneurial spirit effect on franchisor's satisfaction of Weaven and Franzer (2007), Kim (2009), Han (2009), and Yoon etc. (2008). Therefore, when permitting a franchisee, financial condition, management ability, entrepreneurship of the franchisee should be carefully considered. Among relational factors between franchisor and franchisee, trust has the positive influence on the management performance of the franchisor while conflict has a negative effect. However, trust, commitment and conflict factors have been shown not to have any impact on the satisfaction of the franchise headquarters. This result is consistent with the previous studies of Pavlou and Ba (2000), Morrison (1999), Weaven and Frazer (2007), Kim and Park (1994), Sohn (2007) which show that trust between franchisor and the franchisees have a positive effect and that conflict has a negative impact on franchisor's management performance. Other factors causing a negative effective on the franchisor's management performance are a rapid environmental changes and uncertainty in the business. This is consistent with Campbell et al (2007), Kim and Kim (2009), Han and Baek (2008). Finally, the high management performance and satisfaction of the franchise headquarters has a positive effect on the intention of franchise renewal. In the case of large markets such as China, the franchisor's strategy and the role is very important. In this study, we also investigated the characteristics of franchisor and franchisee, relationship, and environmental uncertainty affecting on the management performance and satisfaction of franchisor. Recently, Korean franchises are attempting to enter foreign markets through the rise in popularity of Korean culture and entertainment commonly referred to as the Korean wave. This study provides recommendations for Korean franchises intending on entering the Chinese market. First, in order to achieve stable profits, the franchise corporation needs to support the operation of the individual franchisee through incentives and standardization of services. Second, because trust between the franchisor and franchisee has a positive effect on management performance, on-going discussion and cooperation is necessary to reduce the level of conflict.

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Relationships between Micronutrient Contents in Soils and Crops of Plastic Film House (시설재배 토양과 작물 잎 중의 미량원소 함량 관계)

  • Chung, Jong-Bae;Kim, Bok-Jin;Ryu, Kwan-Sig;Lee, Seung-Ho;Shin, Hyun-Jin;Hwang, Tae-Kyung;Choi, Hee-Youl;Lee, Yong-Woo;Lee, Yoon-Jeong;Kim, Jong-Jib
    • Korean Journal of Environmental Agriculture
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    • v.25 no.3
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    • pp.217-227
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    • 2006
  • Micronutrient status in soils and crops of plastic film house and their relationship were investigated. Total 203 plastic film houses were selected (red pepper, 66; cucumber, 63; tomato, 74) in Yeongnam region and soil and leaf samples were collected. Hot-water extractable B and 0.1 N HCl extractable Cu, Zn, Fe, and Mn in soil samples and total micronutrients in leaf samples were analyzed. Contents Zn, Fe, and Mn in most of the investigated soils were higher than the upper limits of optimum level for general crop cultivation. Contents of Cu in most soils of cucumber and tomato cultivation were higher than the upper limit of optimum level, but Cu contents in about 30% of red pepper cultivation soils were below the sufficient level. Contents of B in most soils of cucumber and tomato were above the sufficient level but in 48% of red pepper cultivation soils B were found to be deficient. Micronutrient contents in leaf of investigated crops were much variable. Contents of B, Fe, and Mn were mostly within the sufficient levels, while in 71% of red pepper samples Cu was under deficient level and in 44% of cucumber samples Cu contents were higher than the upper limit of sufficient level. Contents of Zn in red pepper and cucumber samples were mostly within the sufficient level but in 62% of tomato samples Zn contents were under deficient condition. However, any visible deficiency or toxicity symptoms of micronutrients were not found in the crops. No consistent relationships were found between micronutrient contents in soil and leaf, and this indicates that growth and absorption activity of root and interactions among the nutrients in soil might be important factors in overall micronutrient uptake of crops. For best management of micronutrients in plastic film house, much attention should be focused on the management of soil and plant characteristics which control the micronutrient uptake of crops.

The Results of Curative Radiotherapy for Carcinoma of Uterine cervix (자궁 경부암의 근치적 방사선 치료 및 유도 화학요법과의 병행 치료성적)

  • Kang Ki Mun;Ryu Mi Ryeong;Chang Gee Young;Suh Tae Suk;Yoon Sei Chul;Bahk Yong Whee;Shinn Kyung Sub;Namkoong Sung Eun;Kim Seung Jo
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.149-158
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    • 1993
  • This is a retrospective analysis of 135 patients with invasive carcinoma of the uterine cervix treated with curative radiotherapy from March 1983 through October 1989 at the Department of Therapeutic Radiology, Kang-Nam 51. Mary's Hospital. Among them, 78 patients received radiotherapy alone and 42 patients treated with neoadjuvant chemotherapy followed by radiotherapy and 15 patients were lost to follow up. All patients had follow up from 2 to 106 months (median; 62 months). Age of the patients ranged from 32 to 79 years at presentation (median; 59 years). According to FIGO classification, there were 20 ($16.7{\%}$) in stage IB, 19 ($15.8{\%}$) in stage IIA,49 ($40.8{\%}$) in stage IIB, 5 ($4.2{\%}$) in stage IIIA, 13 ($10.8{\%}$,) in stage IIIB,14 ($11.7{\%}$) in stage IVA. The pathological classification showed 96 ($80.0{\%}$) squamous cell carcinomas, 5 ($4.2{\%}$) adenocarcinomas and 19 ($15.8{\%}$) proven by cytology. The overall 5-year survival rates was $50.8{\%}$, and the 5-year survival rates by stage IB, IIA, IIB, IIIA, IIIB, IVA was $47.7{\%},\;70.2{\%},\;64.1{\%},\;40.0{\%},\;23.1{\%},\;14.3{\%}$, respectively. The 5-year survival rates was noted $51.2{\%}$ of radiotherapy alone and $50.4{\%}$of neoadjuvant chemotherapy followed by radiotherapy. The overall failure rate was $18.3{\%}$(22/120) including $11.7{\%}$ (14/120) locoregional failure, $5.8{\%}$ (7/120) distant metastasis and $0.8{\%}$(1/120) locoregional failure with distant metastasis. Treatment failure rates by the stages were $15{\%}$ (3/20) in stage IB. $10.5{\%}$ (2/19) in stage IIA, $10.2{\%}$, (5/49) in stage IIB, $20{\%}$ (1/5) in stage IIIA, $61.5{\%}$(8/13) in stage IIB, and $28.6{\%}$ (4/14) in stage IVA. The overall complication rate was $34.2{\%}$(41/120) including wet desquamation $7.5{\%}$, (9/120), diarrhea $6.7{\%}(8/120), radiation proctitis $5.8{\%}$(7/120) in decreasing order. A multivariate analysis of factors influencing the survival showed patient age (p < 0.0291), FIGO stage (p<0.0001), Karnofsky performance status (p<0.0043), initial hemoglobin level (p<0.0001), and intracavitary radiation (p<0.0004), but, no significancy in histology (p<0.29) and treatment method (p < 0.87).

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Division of the N2 Stage According to the Multiplicity of the Involved Nodal Stations May be Necessary in the N2-NSCLC Patients Who are Treated with Postoperative Radiotherapy (비소세포성 폐암으로 수술 후 방사선치료가 시행된 N2병기 환자들에서 다발 부위 종격동 림프절 전이 여부에 따른 N2병기 구분의 임상적 의미)

  • Yoon, Hong-In;Kim, Yong-Bae;Lee, Chang-Geol;Lee, Ik-Jae;Kim, Song-Yih;Kim, Jun-Won;Kim, Joo-Hang;Cho, Byung-Chul;Lee, Jin-Gu;Chung, Kyung-Young
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.126-132
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    • 2009
  • Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

The Outbreak of Red Tides in the Coastal Waters off Kohung, Chonnam, Korea 3. The Temporal and Spatial Variations in the Heterotrophic Dinoflagellates and Ciliates in 1997 (전남 고흥 해역의 유해성 적조의 발생연구 3. 1997년도 종속영향성 와편모류와 섬모류의 시공간적 변화)

  • Jeong, Hae-Jin;Park, Jong-Kyu;Kim, Jae-Seong;Kim, Seong-Taek;Yoon, Joo-Eh;Kim, Su-Kyeong;Park, Yong-Min
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.5 no.1
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    • pp.37-46
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    • 2000
  • We investigated the temporal and spatial variations in heterotrophic dinoflagellates (hereafter HTD) and ciliates from June to September 1997 in the waters off Kohung, Korea where red tides dominated by harmful dinoflagellates had occurred from August to October since 1995. We took water samples five times from 5-7 depths at 3 stations in this study period. A total of 17 HTD species were present and of these species in the genus Protoperidinium were 11. The species number of tintinnids (hereafter TIN) present totalled 15 and several naked ciliate (hereafter NC) species were observed. The species numbers of HTD and TIN rapidly increased between August 1st and 21st and then reached to the maximum numbers of 13 and 10, respectively, on August 27 when red tides dominated by Gyrodinium impudicum were first observed in the study area. However the species numbers drastically decreased on September 22. The maximum densities of HTD, TIN, and NC were 45, 39, 57 cells $ml^{-1}$, respectively. ADAS, calculated by averaging the densities of a certain species in the all samples collected from all depths and stations at a sampling period, most increased between August 1st and 21st and then reached to the maximum density of f cells $ml^{-1}$ on August 27 for HTD, while did between August 21st and 27th and up to 7 cells $ml^{-1}$ for TIN. Unlike ADAS of HTD and TIN, that of NC did not change much with the maximum of 8 cells $ml^{-1}$ on August 27th. The pattern of the temperal variation in the species number and ADAS of HTD was similar to that of diatoms and the distributions of Protoperidinium spp. and diatoms had a strong positive correlation. This evidence suggests that HTD, in particular Protoperidinium spp. be a grazer on diatom. In general, the densities of HTD, TIN, and NC decreased with going to stations located in the outer bay. Therefore, the availability of suitable prey and distance from the coastal line might be responsible for the distribution of HTD, TIN, and NC. The results of the present study provide a basis for further experiments for the feeding by dominant HTD, TIN, and NC on dominant phytoplankton including red tide species and for understanding food webs in the planktonic community before, during, and after the red tide outbreak.

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Recognition and attitude to functional division between physicians and pharmacists of practising physicians and pharmacists in Taegu city (대구시 개원의사와 개국약사의 의약분업에 대한 인식과 태도)

  • Lee, Moo-Sik;Yoon, Nung-Ki;Suh, Suk-Kwon;Park, Jae-Yong
    • Journal of Preventive Medicine and Public Health
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    • v.26 no.1 s.41
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    • pp.1-19
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    • 1993
  • Mail questionnaire was administrated to 370 practising physicians and 388 pharmacists in Taegu city selected by systematic sampling to examine utilization states and opinion of pharmacy under medical care insurance programme and the attitude to the functional division between physicians and pharmacists from April to May 1992. Regarding the opinion on the outcome of drug-store under medical insurance, 71.2 percent of practicing physician answered faliure but 13.4 percent of practicing pharmacists answered failure in contrast. Fifty percent of practicing physician asserted introducing functional division between physician and pharmacist while 66.9 percent of practicing pharmacist answered drug-store under medical insurance itself is sucessful programme. Average daily numbers of preparation of medicine was 32.2 case. Percentage of utilization of drug-store under medical issurance to average daily cases of preparing of medicine was 20 percent, percentage of utilization with physician's prescription was 0.7 percent. And 58.7 percent of practicing physician experienced outside the institute prescription. Regarding the opinion on the pros and cons of enforcing functional division between physician and pharmacist, 59.2 percent of practicing physician prefered pros and 17.7 percent cons, but 38 percent of practicing pharmacist prefered pros and 45.5 percent cons. And pharmacist knew better the content of functional division between physician and pharmacist than physician. As a reason for pros of enforcing functional division between physician and pharmacist, practicing physician emphasized to prevent misuse or abuse of medicine but practicing pharmacist emphasized to display physician and pharmacist's professional ability. And as an opinion on implementation style of functional division between physician and pharmacist in pros respondents, practicing physician favored mandatory enforcement (52.3%), while practicing pharmacist favored partial incomplete functional division (81.7%). As the method of prescription if functional division between physician and pharmacist will be enforced, both practicing physician and pharmacist prefered generic name (44.0%, 89%) mostly, but physician prefered brand name (35.3%) secondly. Regarding the reason for not implementing functional division between physician and pharmacist up to date, both physician and pharmacist answered problem of business right between physician and pharmacist, followed by lack of recognition, and interest of people and lack of the govermental willness. Regarding the opinion on prior decision of condition for enforcing functional division between physician and pharmacist, practicing physician and pharmacist named uneven distribution of medical facilities and drug-store between rural and urban, inequality of physician and pharmacist manpower and the problem of manpower demand and supply mostly, and practicing physician pointed out establishing attitude of acceptance on the part of pharmacist and practicing pharmacist favored establishing attitude of acceptance on the part of physician, which was different attitudes between physician and pharmacist. Following conclusion was reached ; 1. Current drug-store under medical insurance program yield insufficient outcome, so we should consider program conversion from drug-store under medical insurance program to functional division between physician and pharmacist. 2. There were problem of business right and conflicts between physician and pharmacist at enforcing functional division between physician and pharmacist, so the goverment should search for formulating plan to resolve the problem and have neutral willness for the protection of the national health.

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A Novel in Vitro Method for the Metabolism Studies of Radiotracers Using Mouse Liver S9 Fraction (생쥐 간 S9 분획을 이용한 방사성추적자 대사물질의 새로운 체외 측정방법)

  • Ryu, Eun-Kyoung;Choe, Yearn-Seong;Kim, Dong-Hyun;Lee, Sang-Yoon;Choi, Yong;Lee, Kyung-Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.325-329
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    • 2004
  • Purpose: Usefulness of mouse liver S9 fraction was evaluated for the measurement of the metabolites in the in vitro metabolism study of $^{18}F$-labeled radiotracers. Materials and Methods: Mouse liver S9 fraction was isolated at au early step in the course of microsome preparation. The in vitro metabolism studies were tarried out by incubating a mixture containing the radiotracer, S9 fraction and NADPH at $37^{\ciirc}C$, and an aliquot of the mixture was analyzed at the indicated time points by radio-TLC. Metabolic defluorination was further confirmed by the incubation with calcium phosphate, a bone mimic. Results: The radiotracer $[^{18}F]1$ underwent metabolic defluorination within 15 min, which was consistent with the results of the in vivo method and the in vitro method using microsome. Radiotracer $[^{18}F]2$ was metabolized to three metabolites including $4-[^{18}F]fluorobenzoic$ acid within 60 min. It is likely that the one of these metabolites at the origin of radio-TLC was identical with the one that obtained from the in vivo and in vitro (microsome) method. Compared with the in vitro method using microsome, the method using S9 fraction gave a similar pattern of the metabolites but with a different ratio, which can be explained by the presence of cytosol in the S9 fraction. Conclusion: These results suggest that the findings of the in vitro metabolism studies using S9 fraction can reflect the in vivo metabolism of novel radiotracers in the liver. Moreover, this method can be used as a tool to determine metabolic defluorination along with calcium phosphate absorption method.

Radioiodine Therapy of Liver Cancer Cell Following Tissue Specific Sodium Iodide Symporter Gene Transfer and Assessment of Therapeutic Efficacy with Optical Imaging (조직 특이 발현 Sodium Iodide Symporter 유전자 이입에 의한 방사성옥소 간암세포 치료와 광학영상을 이용한 치료효과 평가)

  • Jang, Byoung-Kuk;Lee, You-La;Lee, Yong-Jin;Ahn, Sohn-Joo;Ryu, Min-Jung;Yoon, Sun-Mi;Lee, Sang-Woo;Yoo, Jeong-Soo;Cho, Je-Yeol;Lee, Jae-Tae;Ahn, Byeong-Cheol
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.5
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    • pp.383-393
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    • 2008
  • Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.