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Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

  • Lee, JooBuom;Lee, Kyungsun;Choe, Keunbum;Jung, Hyunseob;Cho, Hyunseok;Choi, Kiseok;Kim, Taegon;Kim, Seojin;Lee, Hyeong-Seok;Cha, Mi-Jin;Song, Si-Whan;Lee, Chul Kyu;Chun, Gie-Taek
    • Toxicological Research
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    • v.31 no.4
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    • pp.371-392
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    • 2015
  • TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

The Use of Iron Supplements of Pregnant Women and Pregnancy Outcome (임신부의 철분 보충제 사용과 임신결과)

  • Cho, Ji-Hyun;Ahn, Hong-Seok;Bae, Hyun-Sook
    • Korean Journal of Community Nutrition
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    • v.14 no.3
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    • pp.327-339
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    • 2009
  • It is known that Korean pregnant women take iron supplements at a higher than the recommended level. This study was designed to provide data on current iron intake levels both from food sources and supplement to better guide iron supplement use during pregnancy. We also explored associations of iron supplement intake levels with various sociocultural factors and pregnancy outcomes. Dietary intakes of 510 pregnant women were assessed by a validated 102-item food frequency questionnaire, and information on types and amounts of nutritional supplement intakes were also attained. While dietary intake levels of most nutrients exceeded the KDRIs (Korea Dietary Reference Intakes: EAR: Estimated Average Requirements), folate fell short of the KDRIs. A total of 428 women (83.9%) reported to take iron supplement. The pregnant women were divided into the three groups (group I: Fe supplement intake ${\le}$ EAR, group II: EAR < Fe supplement intake ${\le}$ 3 times of EAR, group III: 3 times of EAR < Fe supplement intake). The mean dietary intake of iron was 24% of the total iron intake for pregnant women. Iron intake from food was not significantly different among I, II, and III. In case of iron intake from supplements, the most frequent dose (34.1%) was 90-100 mg/day, and the mean iron supplement intake was 362% of the EAR. The study findings showed that those with higher levels of iron supplements had better meal quality measured by NAR (Nutrient Adequacy Ratio) and INQ (Index of Nutrient Quality). In addition iron supplement intake levels were significantly related to age (20s: 66.5 ${\pm}$ 38.6 mg/day, 30s: 77.3 ${\pm}$ 47.8 mg/day, p < 0.0116) and experience of childbirth (1st pregnancy: 70.9 ${\pm}$ 41.2 mg/day, 2nd pregnancy: 64.5 ${\pm}$ 39.5 mg/day, ${\ge}$ 3rd pregnancy: 94.4 ${\pm}$ 63.8 mg/day, p < 0.005). However, no significant difference was found between iron supplement intake levels and various pregnancy outcomes including birth weight, birth height, gestational age, weight gain during pregnancy, and jaundice. It is worrisome that iron intake by supplement use greatly exceeded the EAR, suggesting the need of appropriate guidelines for iron supplement intake during pregnancy. Thus iron overdose from supplements in pregnancy should be considered as a serious condition.

Qualitative PCR Detection of GM rices (Milyang 204 and Iksan 483) developed in Korea (국내에서 개발된 GM 쌀 (밀양 204호, 익산 483호)에 대한 정성 PCR 분석법 개발)

  • Kim, Jae-Hwan;Song, Hee-Sung;Jee, Sang-Mi;Ryu, Tae-Hun;Kim, Dong-Hern;Kim, Hae-Yeong
    • Applied Biological Chemistry
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    • v.48 no.4
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    • pp.335-338
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    • 2005
  • For the development of qualitative PCR detection method of genetically modified rice (Oryza sativa L.), rice species specific gene, SAMDC1 (S-adenosylmethionine decarboxylase), was selected and validated as suitable for use as an endogenous reference gene in rice. The primer pair OsSAMDC1-5'/3' with 110 bp amplicon was used for amplification of the rice endogenous gene, SAMDC1 and no amplified product was observed from 19 different plants as templates. Qualitative PCR method was assayed with 2 different GM rices (Milyang 204 and Iksan 483) developed in Korea. For the qualitative PCRs, the construct-specific detection primer pairs were constructed. Os204-5'/OsNOS-3' amplifying the junction region of GUS gene and NOS terminator introduced in Milyang 204 gave rise to an amplicon 172 bp; also, Os483-5'/OsNOS-3' amplifying the junction region of Bar gene and NOS terminator introduced in Iksan 483 gave rise to an amplicon 161 bp.

The research of new Multimedia design developmenton Internet(Focus on the layout) (인터넷에서의 뉴멀티미디어 디자인 개발에 관한 연구 -레이아웃을 중심으로-)

  • 류성현;신계옥;이은주;이현주;배경선
    • Archives of design research
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    • v.20
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    • pp.111-120
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    • 1997
  • Recently, rapidly increasing internet Websites are providing us with the new kinds of multimedia informations without borders acting as the center for exchanging informations. Such new media informations through the internet passes informations via light on the monitor and provides the various informations, with the differentiation from the traditional printing media, it can be searched with electronic commands in limited space. In the process of adapting the new technologies, new media has successfully responded to the fast change and the development of its needs by experiencing the trials and errors, steadily establishing the stable position with its new information transferring and exchanging methods. The representative hompage of websites of information transformations means the first page containing no lower directories and consist of titles, icons, symbols and addresses and can design them in consideration of graphical process, planning, contents and others. Such hompages are very important since the graphical images shows its visual expressions deciding the total meanings of the hompages. In this research, we have analyzed the visual factors of frequencies, ratio of areas, distributions, alignment methodologies on layouts of hompages consisting titles, icons, contents and symbols, etc. from randomly picked samples of 161 hompages of websites in the internets of various areas. Generally, the homepages are designed with graphical expressions in personal way and the feedbacks and responses of such may differs, but we think, this can be used as reference materials for the analysis of new media in objective way. Also, it can be used as the base informations for arrangement and planning of designs with the characteristics of graphics and Graphic User Interfaces in the background which are implemented over internet.

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Monitoring of Pesticide Residues in Special Products (지역특산품 중 잔류농약 실태조사)

  • Kim, Mi-Ra;Na, Mi-Ae;Jung, Woo-Young;Kim, Chang-Soo;Sun, Nam-Kyu;Seo, Eun-Chae;Lee, Eun-Mi;Park, You-Gyoung;Byun, Jung-Ah;Eom, Joon-Ho;Jung, Rae-Seok;Lee, Jin-Ha
    • The Korean Journal of Pesticide Science
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    • v.12 no.4
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    • pp.323-334
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    • 2008
  • This experiment was carried out to analyze for pesticide residues in 17 different types of the special of geographical indication. We purchased 3 cereal grains, nuts and seeds, 3 fruits, 8 vegetables, mushrooms and other plants (Korean medicines) mainly at the agricultural cooperative's joints markets. Total 209 pesticides including multi-analysed pesticides (204) and single-analysed pesticides (5 ; acephate, methamidophos, monocrotophos, omethoate, vamidothion) were analysed with a GC/MS/MS, an HPLC/UVD (PDA) and a GC/FPD. No. 83 method and single-analysed method (Screening of multi-pesticide residue in the special products of geographical indication) of Korea Food Code was selected for validation in recovery and interferences of matrice. The results were as follows: among the selected 17 the special products, the residual pesticides were detected in 8 types of the special products (40 in 302 samples, detection ratio; 13.2%). All of the samples were not detected over MRLs, but tebuconazole, procymidone and isoprothioran were detected with considerable high frequency. These results could be used as KFDA official methods for the analysis of pesticide residues in foods and reference data will be provided to the related institutions.

Ultrasonographic Findings of the Shoulder in Asymptomatic High School Overhead Athletes (무증상 고교 상지 거상 운동 선수의 견관절 초음파 소견)

  • Cho, Su Hyun;Cho, Hyung Lae;Lee, Jung Su;Kim, Jung Woo
    • The Journal of Korean Orthopaedic Ultrasound Society
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    • v.5 no.2
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    • pp.81-88
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    • 2012
  • Purpose: To evaluate the ultrasonographic (US) findings in both shoulders of asymptomatic high school overhead athletes and compare with healthy control. Materials and Methods: 33 individuals (age: $17.5{\pm}1.4$ years) participated in this study. We recruited two groups of high school male athletes, 13 baseball and 10 volleyball players without shoulder pain for recent 6 months as well as one control group of 10 untrained healthy high school students who were age-matched. Ultrasound measurements of thickness of biceps and supraspinatus tendon and acromio-humral distance (AHD) at 0o abduction were taken in dominant and nondominant shoulders. Results: On US examination, subacromial bursa effusion was observed in 5 of the dominant shoulders and in 1 of the nondominant shoulder of 23 overhead athletes and in none of the asymptomatic controls. The thickness of the biceps and supraspinatus tendons and AHD in both shoulders were significantly greater in the athletes than in the controls (P<0.05). We also found that the thickness of the biceps and supraspinatus tendon and AHD of the dominant shoulder were significantly greater than the non-dominant shoulder in overhead athletes (P<0.05), but there were no differences between baseball and volleyball players. Conclusion: Subacromial effusion could be found even in the asymptomatic stage overhead athlete and the thickness of the biceps and supraspinatus tendons and AHD were significantly greater in the overhead athletes than in the healthy controls. Our data is useful reference guide for the ultrasonographic diagnosis of shoulder pathologies occurring in overhead athletes.

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Molecular Characteristics of R Plasmids in Shigella (Shigella R Plasmid의 분자적 특성)

  • Lee, Yoo-Chul;Seol, Sung-Yong;Cho, Dong-Taek;Chun, Do-Ki
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.1
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    • pp.35-53
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    • 1987
  • Multiply resistant Shigella strains isolated in Taegu area were subjected for the characterization of R plasmids. All strains isolated in 1984 and 1985 were susceptible to gentamicin, amikacin, and cephalothin, and most strains were susceptible to kanamycin (Km) and rifampin by agar dilution antimicrobial susceptibility test. The resistance frequency of S. flexneri against ampicillin (Ap) was higher than that of S. sonnei. The strains resistant to sulfisomidine (Su) and trimethoprim (Tp) were found at higher frequency in S. sonnei than in S. flexneri. The most prevalent resistance pattern of S. flexneri was chloramphenicol (Cm) tetracycline (Tc) streptomycin (Sm) Ap, followed by the pattern of CmTcSmSuApTp, CmTcSmSuApTp nalidixic acid, and CmTcSmSuAp in the decreasing order. The antibiogram of CmTcSmSuTp was found to be the most frequent pattern in S. sonnei. The ratio of conjugal transfer of S. flexneri was 47% and 75% of S. sonnei. The average number of plasmid harboring in Shigella was 4 and the size of plasmid ranged 1.3 to 134 megadalton (Mdal). Most S. flexneri carried plasmids of 2 to 3 Mdal and S. sonnei carried those of 3 to 4 Mdal size. The sizes of conjugative plasmids ranged 40-90 Mdal. The incompatibility group (Inc) F II plasmids (54-59 Mdal) were most frequent and rare Inc B plasmids (60 Mdal) of isolates in 1979 and 1980 and Inc FI (87 Mdal) of 1983 isolates were able to be classified by the colony test with standard reference plasmids. The R plasmids of known Inc group were tested for the restriction endonuclease analysis. The pattern of plasmids digested by EcoRl were apparently different by the Inc group but there was no significant difference between species or by the resistance patterns. Nonconjugative plasmids and their phenotypes were identified by transformation test. The transformants were resistant to less than two drugs. Colicin producing transformants carried the Col plasmid of 3.7 or 3.9 Mdal size. $Ap^r$ plasmids derived from S. sonnei were found to be mobilized by transfer factor RT641 to E. coli #CS100. $Ap^r$ plasm ids of same size shared by S. flexneri, S. sonnei, and E. coli were digested with Pstl. All of them showed two restriction fragments of 2.8 kilobase(kb) and 0.7kb. Other plasmids ($Sm^r\;Su^r$) derived from S. flexneri, S. boydii, and S. sonnei were digested with Pstl and they showed same restriction fragment patterns of 3.1kb and 2.9kb. The plasmid profiles of three strains of S. sonnei producing colicin and showing same resistance pattern of CmTcSmSuApTpKm appeared to be similar. Restriction patterns by EcoRl and the behavior of plasmids in conjugation or transformation process were also similar between those plasmids. The restriction patterns were significantly different between the plasmids of Inc FI group and those of unclassified Inc group.

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Matching and Attribute Conflating Method for Linking the Digital Map with the Road Name Address System - Focused on the Road Centerline Layer - (수치지도의 도로명주소 체계 연계를 위한 매칭 및 속성 융합 방안 - 도로중심선 레이어를 중심으로 -)

  • Bang, Yoonsik;Ga, Chillo;Yu, Kiyun
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.30 no.4
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    • pp.379-388
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    • 2012
  • The Road Name Address system has begun to be applied and widely used since 2011. However, the Digital Map, or the national representative basic map, has no reference to the Road Name Address system. It causes some difficulties to use the Digital Map under the Road Name Address system. In this paper, we suggest a method for generating the expanded Digital Map by adding information about Road Name Address system into the objects of the Digital Map. First, object matching pairs between the road section layer from the Road Name Address Map and the road centerline layer from the Digital Map are found. Then attributes to be copied from the Road Name Address map to the Digital Map are extracted by comparing their attribute tables. Finally the extracted attributes are copied from the Road Name Address Map to the Digital Map. The expanded road centerline layer of the Digital Map then has attributes about road name according to the Road Name Address system, so that the georeferencing of the Digital Map according to the Road Name Address system becomes possible.

Efficacy of Fine Needle Aspiration Biopsy in Parotid Gland Tumors (이하선 종양에서 세침흡인검사의 유용성)

  • Lee, Chang-Hee;Lee, Hyun-Sub;Jin, Sung-Min;Lee, Sang-Hyuk;Pyo, Jung-Soo;Sohn, Jin-Hee
    • Korean Journal of Head & Neck Oncology
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    • v.27 no.2
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    • pp.204-209
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    • 2011
  • Background and Objectives : The usefulness of fine needle aspiration biopsy(FNAB) for diagnosis of parotid gland tumors is controversial, because of the generalized belief requiring surgery for most parotid tumors. The aim of this study was to evaluate the efficacy of FNAB for diagnosis in parotid gland tumors. Material and Methods : FNAB was performed in 91 patients who underwent parotid surgery at Kangbuk Samsung Hospital from January 2007 to December 2010. The result of FNAB, 11 malignancies and 75 benign tumors and 5 non-neoplasms were analyzed and compared with the final histopathologic diagnoses. Sensitivity, specificity, accuracy, positive predictive value(PPV), and negative predictive value(NPV) were calculated using final histopathologic diagnosis of the surgical specimen as the standard diagnostic reference for comparative analysis. Results : 86 specimens(94.5%) were suitable for evaluation. We compared the result of FNAB and the final histopathology in 79(89.4%) cases. The sensitivity, specificity, accuracy, PPV, and NPV of FNAB for detecting pleomorphic adenoma was 95.8%, 88.4%, 92.3%, 90.2%, and 95.0%. In Warthin's tumor, results were 86.4%, 94.2%, 92.3%, 82.6%, and 95.6%. Among 11 patients who were diagnosed with malignancy on final histopathologic report, only 3(30%) patients were diagnosed with the same as on FNAB, the other 8 patients were initially diagnosed incorrectly as benign tumors in FNAB. There were no complications related to FNAB. Conclusion : Diagnostic accuracy for FNAB in benign parotid tumors was high. However, in malignant tumors, FNAB shows low diagnostic usefulness compared with benign tumors. FNAB can be effective and safe diagnostic technique for evaluating the benign parotid glands tumors.

Growth performance and, blood metabolites and leukocytes of growing pigs fed with fermented hulless barley (발효 쌀보리의 급여가 육성돈의 혈중 대사산물, 혈구조성 및 생산성에 미치는 영향)

  • Jeong, Yong Dae;Kim, Ki Hyun;Min, Ye Jin;Kim, Young Hwa;Yu, Dong Jo;Cho, Kyu Ho;Kim, Doo Wan
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.8
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    • pp.295-302
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    • 2018
  • This study was conducted to investigate effect of feeding fermented hulless barley (FHB) on growth performance and blood metabolites in growing pigs. Forty-five pigs (LYD; initial body weight, $30.33{\pm}0.05kg$) were randomly allotted into three dietary treatments that consisted of 0, 0.5 and 1.0% of the FHB in the basal diets. The pigs fed 0.5% FHB showed higher average daily gain than the 0 and 1% FHB treatments, although there was not significant among the treatments. Similarly, average daily feed intake and feed conversion ratio were not different among the treatments. Blood white blood cells, neutrophil, lymphocyte, monocyte, eosinophil and basophil were ranged to reference values, but not difference among the treatments. Serum glucose was increased in the control compared with 0.5 and 1.0% FHB. However, parameters related to protein, lipid and mineral also were not different among the treatments. These results indicate the FHB has no significant effect of growth performance and metabolizable responses in growing-finishing pigs.